Livestock Research for Rural Development 24 (9) 2012 Guide for preparation of papers LRRD Newsletter

Citation of this paper

Under nutrition in the ewe: Foeto-placental adaptation, and modulation of lamb birth weight: A review

W Addah*, P K Karikari** and J Baah

Agriculture and Agri-Food Canada, Lethbridge Research Centre
P. O. Box 3000, 5403 -1st Avenue South
Lethbridge, Alberta T1J 4B1, Canada
* Permanent Address: University for Development Studies, P. O. Box TL 1882, Tamale Ghana
** Department of Animal Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana


Knowledge of the period of pregnancy when under nutrition is likely to have the severest impact on ovine intrauterine growth is necessary to reduce the adverse effects of under nutrition on reproduction while at the same time optimizing feed intake and feed cost. Major changes in intrauterine growth occurs from day 0–45 (first trimester), day 45–90 (second trimester) and day 90–147 (third trimester) of gestation.

Higher energy intake during the first trimester has deleterious effects on oocyte quality and embryo survival through its effects on progesterone concentration and uterine pH; on the contrary, under nutrition at this time may “programme” poor adult growth and productivity of the progeny. Moderate undernutrition in ewes in good body condition that results in a small loss of body condition score (≤ 0.5) in the second trimester has no detectable detrimental effects on weights of lambs at birth compared to adequately and overnourished ewes. Effects of under nutrition on foetal growth in the third trimester can however be severe with adverse longterm effects on milk and colostrum yield leading to poor pre weaning lamb growth rate and higher rates of mortality. For ewes in good body condition, undernutrition in the second trimester may have lesser adverse effects on foeto placental growth compared to under nutrition in other trimesters. The direct effects of heat stress together with lower natural forage quality in tropical conditions suggest that the effects of undernutrition on foetal losses may be greater in tropical than temperate regions.

Key words: lamb birth weight, foetal growth, ovine pregnancy, trimester, undernutrition


The ewe has widely been used as an experimental model for assessing the effects of maternal under–nutrition on intrauterine growth restriction (IUGR) because unlike other animals such as rodents, the functional responses of the ovine foetus to short and long term placental deficiency can be studied in utero and the biological responses of the ewe to under–nutrition are similar to those in humans (Leiser et al 1997; Morrison et al 2008).  

Notwithstanding the difficulty of clearly delineating gestation into separate distinct phases, the effects of ovine maternal under–nutrition on intrauterine growth have often been assessed during three phases of gestation when significant changes in the conceptus can empirically be measured: the first trimester (~ day 0–45) when oocyte quality, number of blastocysts and placentomes are established, the second trimester (~ day 45–90) when there is increased proliferative growth of the placenta and the third trimester (~ day 90–147) when rapid foetal growth occurs (Russel 1984; Osgerby et al 2002; Addah and Karikari 2008). Nutritional management of the ewe during these periods can have a significant impact on the outcome of ovine pregnancies given that maternal nutrition has greater consequence on intrauterine growth compared to genotype during prenatal growth (Bauer et al 1998). 

The effects of maternal nutrition on gestation are complex and responses to under–nutrition have often been inconsistent. Maternal nutrient pool is the main source of nutrition for the conceptus. However, restriction of maternal nutrient intake may alter nutrient partitioning and skew intrauterine growth and development without affecting lamb weight at birth. This insensitivity has warranted the supposition that weight at birth should not be used as an index of maternal nutritional status during pregnancy (McCrabb et al 1991; Harding et al 1992; Harding and Johnson 1995; Osgerby et al 2002). Skewed development of the foetus can have permanent ramifications on the adult life of the conceptus, a phenomenon often described as foetal programming in which permanent changes in metabolism and growth of tissues or organs of the foetus ultimately affect the immunity, growth, and carcass and meat characteristics of the adult adversely (Robinson et al 1999; Osgerby et al 2002). Nonetheless, nutritional restriction in any of three trimesters of pregnancy have either increased (Holst and Allan 1992; Addah and Karikari 2008) or decreased (Borowczky et al 2006; Gardner et al 2007) lamb weights at birth.  

Maternal nutritional status can also be assessed by measuring maternal blood metabolites (1984). Several blood metabolites including glucose, lactate and amino acids have been used as indices of maternal nutritional adequacy or under–nutrition during pregnancy but there seems to be no general agreement on which metabolite to use and at what stage of pregnancy their concentrations are most critical to the growth of the conceptus (Robinson et al 1999).  

It is also difficult to ascertain which trimester of ovine pregnancy is most susceptible to maternal under–nutrition. While the nutrition of the ewe during the first trimester has been considered as the most critical stage of gestation due to its effects on oocyte quality and embryo viability (Robinson et al 1999; 2002; Borowczky et al 2006), the second trimester is the period of rapid proliferative tissue growth and DNA synthesis of the placenta, which affects nutrients transport to the foetus (Ehrardt and Bell 1995). Nearly 75–80% of ovine foetal growth occurs in the last trimester (Wallace 2004) and this is usually accompanied by higher nutrient demand (Schloesser et al 1993). Under–nutrition during this stage has therefore been found to compromise lactational yield and neo– and peri– natal growth rate resulting in reduced lamb vigour and survival rates (McDonald et al 1995; Abassa 1995). Thus, despite many studies on the effects of under–nutrition on IUGR, there appears to be no common agreement of the stage of gestation that requires the utmost nutritional attention. This review examined ovine foeto–placental adaptation to under–nutrition during the first, second and third trimesters of pregnancy. The scope of this review also includes the effects of maternal under–nutrition on perinatal lamb performance. 

Placental adaptation to under nutrition, and modulation of intrauterine growth

The ovine placenta is attached by discrete points to the uterine wall by connective tissues called caruncles. The conceptus is in turn attached to the placenta by a discrete number of chorionic villi called foetal cotyledons (placentomes). These cotyledons are the main conduit by which the conceptus uptakes its nutrients. The number of foetal cotyledons and the relative proportion of maternal or foetal tissue in each cotyledon are influenced by maternal under–nutrition (Steyn et al 2001; Wallace et al 2001; Figure 1). Foetal growth is therefore largely dependent on the amount and rate at which the placenta delivers substrates to the foetus. The placenta however has the ability to modify substrates into forms that are directly unavailable in the maternal pool and therefore deficient at the foetal side of the placenta, for foetal use. The placenta is therefore considered to have a maternally–independent metabolism function (Owens 1991).  

The main factors affecting placental transport capacity include morphology, size, nutrient and hormone syntheses and metabolism, and nutrient transporter systems (Fowden 2006). For example even though ovine and swine placenta are epitheliochorial (uterine epithelium and the chorion of the foetus are in contact), the utero–foetal interface is limited to discrete placentomes in the ewe and the number of placentomes per foetus plays a major role in determining the overall severity of under–nutrition on foetal growth (Robinson and Symounds 1995) whereas in swine, placental exchange area is diffused over the entire surface of the uterus facilitating greater nutrient transport capacity (Fowden, et al 2006).


Figure 1. Vatnick’s morphological classification of cotyledons (A, B, C and D) based on the relative proportion of foetal (black; ●) and maternal (white; ○) tissues. The proportion of foetal tissue increases from type A to D (Vatnick et al 1990; Steyn et al 2001).

Although large foetuses from in vitro embryo cultures do not necessarily have large placentae (Robinson et al 1999) and foetal weight is not often influenced by placental weight alone in normal pregnancies (McCrabb et al 1986), there is nonetheless a positive correlation between placental weight and foetal or lamb birth weight in both nutrient–intake restricted and unrestricted ewes (Figure 2; Steyn et al 2001; Wallace et al 1996; 2004) with variation in placental weight explaining up to 80% and 67% of the variation in foetal weight during early gestation (Morrison 2008) and at birth (Mellor 1983), respectively. The importance of placental nutrition to the modulation of foetal growth is further demonstrated by the fact that its nutrient requirements are often greater than that of the foetus. The uptake of glucose by the gravid uterus is greater than the estimated glucose utilized by the foetus even though the placenta represents only ~10% of the total mass of the gravid uterus. Consumption of glucose by non–foetal conceptus tissues during the third trimester of pregnancy accounts for about two–thirds of the total glucose uptake by the gravid uterus; the foetus utilizes less than 50% of the glucose taken up by the gravid uterus with the rest consumed by the utero–placental tissues (Brockman 1993; Bell and Bauman 1997). Other studies show that up to 80% of glucose and oxygen taken up by the gravid uterus are consumed by the utero–placental tissues during mid–gestation (Bell et al 1986). Rapid proliferative growth of the placenta occurs between approximately 40 and 80 days, plateaus between 75–80 days (Ehrhardt and Bell 1995) and ceases growth at about day 104 when the foetus has attained 30% of its final birth weight (Wallace et al 1999). However, placental growth as indicated by placental DNA content is highest in the first trimester. The placenta then continues to develop through structural and biochemical changes in the second and third trimesters during which these changes ensure that placental function parallels foetal growth through increased blood flow rates, greater surface area for nutrient exchange, greater permeability to urea, and glucose transfer until the end of gestation (Owens 1991). The period of greater placental growth therefore corresponds with its peak in nutrient requirements. Thus, in addition to its vital function of maternal–foetal glucose transport, the placenta is a major contributor to the increased glucose demands on the pregnant animal (Bell and Bauman 1997).


Figure 2. The effects of restricting feed intake during different trimesters of pregnancy on the relationship between placental and birth weights (Data from Addah and Karikari 2008)

Restoration of adequate nutrition on or before day 40 of ovine gestation, well before placental size plateaus, appears to have only temporary effects on placental and foetal growth and is not detectable at birth (Robinson 1990). This suggests that the influence of under–nutrition in early pregnancy on the conceptus may be marginal. However, retarded muscle and bone growth due to under–nutrition in the first trimester of pregnancy (Osgerby et al 2002; Costello et al 2008) suggests that the effects of early maternal under–nutrition on productivity has a more greater economic consequence than weight at birth per se since maternal nutrition can influence prenatal and adult development without influencing birth weight (Vonnahme 2007; Hausman 2009). Studies on the effects of a 70% reduction in maternal maintenance requirements on the weights of different foetal body parts indicate greater effects on foetal muscle (myogenesis) and bone growth compared to the brain and heart during different trimesters of pregnancy (Nordby et al 1987; Osgerby et al 2002; Costello et al 2008) suggesting a greater priority in nutrient partitioning in favour of the foetal brain and heart compared to muscle growth. Similarly, in cattle, steers born of under–nourished cows did not only have lower live and carcass weights compared to those born of adequately fed cows but also had lesser retail carcass yield based on indices of fatness (Greenwood et al 2004). McCrabb et al (1991) however did not find any adverse effects on the weights of the foetal brain, heart and liver when ewes were under–nourished (loss of 121 g/day) in the second or third trimesters of pregnancy.  

The various effects of maternal under–nutrition on placental and foetal growth during the three trimesters of pregnancy are shown in Table 1. Responses to under–nutrition have generally been inconsistent. Efforts to determine the effects of under–nutrition on foetal growth have generally concentrated on the second trimester, possibly because of the rapid growth of foeto–placental tissues during this period. Maternal nutrient restriction in mid gestation has been found to improve birth weight in adolescent West African Dwarf (WAD; Addah and Karikari 2008) and other sheep breeds (Wallace et al 1996; 1997; 2004) and has earlier been recommended as an economic  feeding strategy for pregnant ewes since it had no distinguishable adverse effects on birth and weaning weights of lambs (Holst and Allan 1992) although they may have poor muscle conformity in adult life, an economic trait most valuable to farmers (Nordby et al 1987; Osgerby et al 2002). Other literature indicate that though under–nutrition during the first trimester of pregnancy may have detrimental effects on placental size and development, it enhances blood flow between the placenta and foetus leading to improved foetal growth (Robinson et al 1999; Wallace et al 2001). This is because IUGR is the result of reduced umbilical blood flow which in turn reduces foetal substrate supply (Morrison 2008). A 70% restriction of maintenance nutrient requirement significantly decreased placental weight, and altered its morphology (less proportion of foetal tissues) and the growth of various foetal organs between 90 and 135 day of gestation (Osgerby et al 2002) but a restriction in feed intake meant to induce 121 g/day loss in maternal weight between d 30 and 96 of gestation increased placental weight by 21% at the 96th and 104th day of gestation (McCrabb et al 1991). However, none of these studies detected a corresponding effect of these perturbations on foetal weight, partly confirming the hypothesis that foetal weight may be insensitive to nutritional restriction and therefore should not be considered as a good index of nutritional status and productivity (Harding and Johnston 1995; Vonnahme 2007).


Conversion of glucose to lactate is an important adaptation to under–nutrition that provides energy for intrauterine growth during periods of nutritional stress. A 20% deficit in foeto–placental glucose requirements is compensated for by a three–fold increase in foetal lactate consumption from the placenta (Harding and Johnston 1995). The placenta maintains energy supply to the foetus during periods of high foetal energy demand by increasing the net production of lactate from glucose and the release of lactate into umbilical circulation. This entraps lactate in umbilical circulation for foetal metabolism alone since umbilical tissue is less permeable to lactate than glucose. This phenomenon has been described as placental sequestration of essential substrates (Owens 1991). A similar mechanism has been described for amino acids (Cetin 2001). However in in vitro studies, mammalian cell growth is inhibited at higher lactate concentrations (≥ 40 mmol/L) though such levels of concentration are hardly reached in normal growing cells (Pötner 2009). 


Glutamine is an energy source for rapidly developing and immune mammalian cells. It stimulates anabolic conditions in muscle cells and increases the rate of protein synthesis while slowing the breakdown of glycogen. There is evidence that under conditions of high nutrient demand or nutritional stress, the foetus synthesizes substantial amounts of glutamate and serine and utilizes ~ 50% (Battaglia 2000; Narkewicz et al 1996) of these for growth. The rest is shuttled back to be resynthesized by the utero–placental tissue into glutamine and glycine, and then transported back to the foetal liver again to be partly (45%) metabolized into serine and glutamate for foetal use, often described as the glutamine–glutamate shuttle (Figure 3; Neu 2001; Cetin 2001). This remarkable metabolic versatility of glutamate and glycine has been demonstrated and explains the reason for high foetal glutamate and serine concentrations though there is no umbilical uptake of serine and glutamate from maternal sources during periods of imposed under–nutrition (Brosnan 2000; Neu 2001). The foeto–placental biosynthesis, shuttle and utilization of glutamate and serine have thus been postulated as mechanism by which the ovine foetus can adapt to amino acid deficiency (Narkewicz et al 1996). Battaglia (2000) reported that approximately 19% of placental nitrogen uptake was derived from glutamine by a 130–day gestated foetus. 

The ultimate benefits of these foeto–placental adaptations are not well understood. Glucose, the primary energy source for the foetus yields 36 mole of ATP per mole of glucose oxidized while complete oxidation of glutamine yields 21 ATPs per mole. The shortfall of ATP generated per mole of glutamine oxidized is however made up by the high flux of glutamine oxidized from glutamate passed into foetal circulation. The metabolism of glutamine also generates high concentration of ammonia that may inhibit foetal cell growth. In in vitro mammalian cell studies, 5–6 mmol/L ammonia has been reported to reduce cell growth rate by 50% (Pötner 2009). Placental transamination of branched chain amino acids, a major source of energy, may therefore be another pathway by which placental demand on glucose is reduced for the glucose to be redirected to the foetus (Owens 1991; Figure 3) since the energy yield from glucose is greater than that from transamination of amino acids.


Figure 3. Foeto–placental metabolism of glutamate and glutamine in response to under–nutrition. TCA = tricarboxylic acid cycle (Modified from: Neu 2001 with permission of the author)


Contrary to the positive correlation between placental mass and foetal growth, some studies suggest that on weight–specific basis, a smaller placenta produces more lactate and increases its availability to the foetus than larger ones (Owens 1991). This was later supported by findings which attributed the placental restriction of foetal growth in mid pregnancy to inadequate growth (size) and vascularisation of the placenta rather than to alterations in its nutrient metabolism and transport capacity (Wallace et al 2004). Similarly, McCrabb et al (1991) also observed that higher placental weight per se was not linearly correlated with higher foetal weight; instead, it was its functional capacity for uptake, metabolism and transport of nutrients that modulated foetal growth.  

The main mechanism by which the placenta modulates the effects of under–nutrition on the foetus includes 1) enhanced transfer capacity 2) efficient utilization of nutrients for growth and function and 3) modification or transformation of limiting substrates. Maternal nutrition may also influence the endocrinology of the maternal–placental–foetal axis, however, the major effects of foetal endocrine secretions on foetal growth are those that regulate or are regulated by nutrition rather than those directly regulated by pituitary function per se (Owens 1991).


Table 1 Effects of under–nutrition during different trimesters of ovine pregnancy on placental and lamb birth weight


Birth weight

Placental        weight

 Degree of maternal under nutrition

Nutritional modulation of  foetal growth/birth weight








No supplementary feeding

Foetal growth is less sensitive to under–nutrition at this stage.

Addah et  al (2007)

Addah and Karikari (2008)



245 g  loss in average daily gain (ADG) compared to ewes on high feed intake

Placental weight was higher than those on high diet.

Reduction in cotyledon number.

Wallace et al (1999)1



15% restriction of recommended nutrient intake

2Morphological adaptation/alteration of the placenta to under–nutrition: increased proportion of foetal tissue of the placentomes than of maternal tissue

Steyn et al (2001)





Loss of 0.8 body condition score

Foetal growth is dependent on placental growth and commencing under–nutrition at d 90 of gestation does not adversely affect placental growth if optimal nutrition is restored in the third trimester.

Holst and Allen (1992)



Loss of 2.8 kg  live weight

Moderate level restriction of intake in matured ewes followed high intake in the third trimester counteracts the effects of under–nutrition in the second trimester leading to higher birth weight.

Wilkinson and Chesnutt (1988)



50–60% restriction of recommended ME intake

Maternal “buffering” of the effects of under–nutrition due to a good pre–conception body condition score.

Gardner et al (2007)





121 g  loss in ADG

3Nutrient partitioning in favour of the foetus and buffering of foetal growth by mobilization of maternal body tissues.

 Placental growth and transport capacity are independent of maternal nutritional status.

McCrabb et al (1991)



No supplementary feeding

Restriction of feed intake stimulates placental growth and nutrient transport capacity resulting in heavier lambs at birth.

Addah et al (2006)1;

 Addah and Karikari (2008)1


60% restriction of recommended nutrient requirement

Altered glucose concentration reduces foetal gut development resulting lower birth weight in IUGR lambs compared to non–restricted.


Hammer et al (2011)



245 g  loss in  ADG compared to high–fed ewes

Stimulates placental growth and increases foetal cotyledon weight compared to those on high intake.

Wallace et al (1999)1




33%  restriction of metabolisable energy (ME) intake requirements

A deficit of 1% of ME intake requirements results in 0.3% reduction in lamb birth weight.

Lower maternal plasma glucose concentration is associated with lower lamb birth weight.

Adu and Olaloku (1979)


40–60% restriction of  ME  intake requirements

Lower energy intake at a time when absolute foetal growth is greatest decreases lamb birth weight.

Gardner et al (2007)

70% reduction in maintenance requirements

4Alteration in placental weight and placentome morphology

Reduced supply of substrates (e.g. glucose and amino acids) to foetus.

Osgerby et al (2002)



Rapid vs. low growth rate

4Improved uterine and umbilical blood and oxygen transport rates.

Increased placentome number and weight resulting in greater foetal weight.

Wallace et al (2002)1

Full term pregnancy



196 g loss in  ADG compared to high–fed ewes

Moderate under–nutrition stimulates placental growth, umbilical blood flow thereby increasing foetal growth.

Wallace et al (2001)1

No supplementary feeding

Chronically severe under–nutrition beyond the maternal–foetal–placental adaptations.

Addah et al (2006)1

Addah and Karikari (2008)1

Effects of under–nutrition: + = increased growth; – = reduced growth; ± = no effect (p= >0.01 – 0.05); ND= not determined.

1Adolescent ewe.

2First 70 days of gestation.

3Foetal weight at 140 day of gestation.

4Foetal weight at 134–135 day of gestation.

Concentrations of maternal blood metabolites as indicators of nutritional status during pregnancy

Changes in maternal body condition and weight gain during pregnancy may not represent a good measure of the adequacy of foetal nutrition given that greater maternal growth rate and fat deposition can occur due to skewed nutrient partitioning in favour of maternal tissues at the expense of the gravid uterus as commonly observed in adolescent ewes (Wallace et al 2002; 2004; Addah et al 2007; Addah and Karikari 2008). The concentrations of blood metabolites during pregnancy therefore offer a better means of assessing the nutritional status of the ewe than changes in weight gain per se. The chemical composition of blood is often under homeostatic control. Variations in its composition are therefore often maintained within narrow limits (O`Doherty and Crosby 1998). However several factors operate against this equilibrium and when such factors become severe, homeostatic mechanisms are unable to adequately maintain this balance and deviations from the normal concentrations occur. A more immediate assessment of the adequacy of foeto–maternal nutrition is afforded by the measurement of some maternal blood metabolites (Russel 1984).  

Several maternal blood constituents have been used as indices of maternal nutritional adequacy or under–nutrition in the WAD sheep (Adu and Olalou 1979; Tuah and Klusey 1992; Addah and Karikari 2008) and other breeds (Russel 1984; Schloesser et al 1993; O`Doherty and Crosby 1998; O`Callaghan and Boland 1999) but there seems to be no general agreement on the stage of pregnancy at which the concentration of one or more of these is most critical to the growth of the conceptus (Robinson et al 1999). This could be due to the confounding effects of factors such as type of species, age, parity, utero–placental morphology and maternal reserves or body condition of experimental subjects used among studies (McCrabb et al 1991).  

The metabolite most suitable for assessing the adequacy of nutrition may also vary depending on the stage of pregnancy. The metabolites which have been identified as indices of nutritional adequacy in pregnant ewes include glucose and total protein (Adu and Olaloku 1979; Robinson et al1999; Tuah and Klusey 1992), lactate (Bell and Bauman 1997; Bauer et al 1998), ammonia and urea (Tuah and Klusey 1992; Schlosser et al 1993; O`Doherty and Crosby 1998; O`Callaghan and Boland 1999), and ketone bodies (acetoacetic acid, β–hydroxybutyric acid and acetone; Adu and Olaloku 1979; Russel 1984; O`Doherty and Crosby 1998; Schlosser et al 1993). However those that contribute substantially to the energy and protein requirements of ruminant foetuses are glucose and lactate, and amino acids respectively. Glucose and oxygen are the primary substrates for foetal growth (Owens 1991). In order of importance, the foetus in the third trimester of gestation derives approximately 50%, 20–40% and 10–30% of its total energy requirements from glucose, lactate and amino acids, respectively (Bauer et al 1998). Blood glucose concentration therefore offers a direct measure of the energy that is readily available to the foetus. However compared to glucose, plasma 3-hydroxybutyrate, has been identified as the most reliable indicator of nutritional status during pregnancy. This is because its concentration does not subject to much variability due to extraneous conditions such as the stress of animal handling and blood sampling (Russel 1984).  

Tuah and Klusey (1992) found plasma glucose concentration of non–pregnant WAD ewes to be 50% lower than in pregnant ewes, and attributed this to heavy demands of the foetus on the maternal glucose pool during pregnancy. Using the same breed, Adu and Olaloku (1979) found higher plasma glucose concentration for ewes receiving adequate nutrition (527–538 mg/L) and lower concentration (384 mg/L) for moderately malnourished ewes during the last 7 weeks of gestation. In adolescent ewes, plasma glucose was lower in moderate– compared to high–intake ewes during the three trimesters of pregnancy after 2.5 h of feeding (Wallace et al 1999).  

Total plasma protein concentration has also been shown not to differ between pregnant (4th and 5th month) and non–pregnant WAD ewes (Tuah and Klusey 1992) but Schloesser et al (1993) reported an 11.5% decrease in mean plasma protein concentration between early pregnancy and mid pregnancy when ewes were supplemented with varying levels of soya bean meal.  

Short–chain fatty acids are poorly transported across the placenta in sheep. This is because while placental glucose and lactate are transported by facilitated diffusion and therefore their concentrations in foetal blood are not entirely dependant on maternal–foetal plasma concentrations, maternal acetate is presumably transported by passive diffusion and makes only a minor contribution to foetal metabolism (Brockman 1993). Compared to ATP yield from glucose, acetate contributes less than 2% of ATP to a 19-day embryo and is not metabolized by embryos at the very early stage of cleavage (Robinson and Symounds 1995). In hyperketonaemic ewes, ketones are poorly transported across the placenta while amino acids are transported from maternal blood to placenta by active transport but are subsequently transported to the foetus by passive transport (Brockman 1993). Little is known about the contribution of free fatty acids to foetal metabolism but high foetal fat in some species suggest that our understanding of the contribution of free fatty acids to foetal energy metabolism is constrained by methodological limitations rather than its actual contribution to foetal metabolism (Owens 1991). 

The transport of calcium across the placenta to the foetus is endocrinologically regulated by the foetal parathyroid gland through the secretion of parathyroid hormone and a parathyroid hormone–like protein that may maintain higher calcium levels in the foetus relative to maternal calcium concentration (Loveridge et al 1988). The foetal skeleton is the main sink for maternal calcium and maternal calcium has been used to estimate foetal growth during pregnancy (McCrabb et al 1991). Deficiency of cobalt during the first trimester of pregnancy may also result in reduced lamb vigour and regression in the acquisition of passive immunity since lambs are unable to stand on their feet to suckle the needed colostrum after birth. This “programmed” negative effect is not reversed even when the deficiency is corrected in later trimesters (Robinson et al 1999). Selenium and vitamin E deficiencies are also associated with embryo mortalities and reduction in birth weight.


Plasma albumins are very important in gestation and their concentration generally decreases particularly in the last week of pregnancy (O’Doherty and Crosby 1998). 

α-foetoglobulins found in foetal plasma and amniotic fluid is also a major binding site for fatty acids, tryptophan, Ca2+ and  steroid hormones. β–globulins contain transferin which binds and transports Cu2+, Zn2+ and Fe2+. This makes maternal globulins very important during pregnancy. In pregnant WAD sheep, maternal plasma globulins concentration was lower for ewes whose intake was restricted throughout pregnancy compared to those restricted in only the first or second trimesters but was higher than in ewes restricted in third trimester or non–restricted throughout pregnancy (Addah and Karikari 2008). O’Doherty and Crosby (1998) found progressive decline in concentration of serum globulins as pregnancy advanced.


The role of IGF-II in controlling foetal growth is largely undisputed but whether this control is exerted directly or via its effects on placental growth is not certain (Owens 1991). High concentration of plasma insulin and IGF-I in well–fed ewes provide an anabolic stimulus to maternal tissues accretion at the expense of placental growth (Wallace et al 1999). Though this mechanism is relatively less understood, it remains as one of many possible hypotheses for explaining the retarded growth of the placenta in well–nourished adolescent ewes restricted in the second trimester. 

Effects of under–nutrition on intrauterine growth during the first trimester

Except under management systems where there are controlled mating programmes, sheep in the early stages of pregnancy are not often fed with the intention of optimizing their early pregnancy requirements, consequently, most studies examining the impact of ovine under–nutrition on IUGR have focused on the second and last trimesters of pregnancy when most of the increase in placental and foetal size occurs. However, through its impact on pre–implanted oocytes (McEvoy et al 1997; Borowczyk et al 2006; Castello et al 2008), and embryo and placental development (Robinson et al 1999; 2002), nutrition in early pregnancy may profoundly affect embryo viability and foetal growth and development through its effects on maternal progesterone concentration (O`Callaghan and Boland 1999). Increased dietary energy intake in sheep for a relatively short time will increase the rate of ovulation by increasing gonadotropin secretion but high nutrition during early pregnancy generally has a negative effect on oocyte (Borowczyk et al 2006) and embryo quality (O`Callaghan and Boland 1999). Lower rates of fertilization, poor oocyte viability and quality, and lower rates of blastocyst cleavage and formation have been observed in ewes whose intake was restricted by 60% compared to the control (Borowczyk et al 2006). Under–nutrition in early pregnancy may also programme the foetal ovary (Robinson et al 1999), and bone and muscle development with consequences for adult body conformation and carcass quality (Osgerby et al 2002; Greenwood 2007).  

Reduced foetal growth and muscle development are usually the result of under–nutrition during early pregnancy because the establishment of muscle fibres primarily occurs early in foetal development and remains permanent thereafter (Robinson et al 1999; Vonnahme 2007). The ovine placenta is cotyledonary (Figure 1), hence reduction in the size and number of cotyledons due to under–nutrition will reduce the transport capacity of the placenta and restrict foetal growth. Moderate restriction in feed intake resulting in gain of 55 g/d compared to unrestricted ewes gaining 300 g/d in the first trimester significantly increased foetal cotyledon numbers (Wallace et al 1999) but Steyn et al (2001) found no difference between the placental weights of ewes whose nutrient intake was moderately restricted (15%) compared to those that received their full nutrient requirement during the first 70 days of gestation. 

The effects of under–nutrition in early pregnancy could also adversely affect foetal growth in later gestation; for example, poor placental development early in pregnancy may also lead to a chronic reduction of substrate delivery for optimal foetal growth in late gestation (Morrison 2008). Foetal cotyledon numbers have similarly been found to be lower in ewes maintained on a higher dietary energy intake regime in the first trimester with no compensatory placental growth occurring in ewes maintained on a high dietary energy intake thereafter during the second and third trimesters (Wallace et al 1999). 

High blood glucose and urea concentrations are deleterious to embryo development (Furnus et al 1996; McEvoy et al 1997; O`Callaghan and Boland 1999) because toxic by–products of nitrogen metabolism, such as ammonium ions increase intrauterine pH and impair embryo survival especially when the diet offered contains higher proportion of rumen degradable protein than carbohydrates. Foetal thoracic girth and gut weight  were increased  in the first trimester, unchanged in the second but reduced in the third trimester when the daily maintenance requirements of ewes were restricted by 70% compared those whose requirements were fully met (Osgerby et al 2002). The density of foetal myofibres and number of blood capillaries in the foetal triceps brachii were reduced in Welsh mountain ewes whose feed intake was restricted by 60% at the pre–implantation stage of pregnancy (Costello et al 2008).

These data suggest that under–nutrition in early pregnancy can influence birth weight as well as adult body conformation given that the net number of muscle fibres formed prenatally remain unchanged in adult life. 

Effects of under–nutrition on intrauterine growth during the second trimester

The second trimester of pregnancy represents the period when the metabolic rates of the placenta, the foetus and its rapidly developing visceral organs are at their peak (Kelly 1992; Robinson and Symonds 1995). Data from studies by Ehrhardt and Bell (1995) show that ovine foetal weight increases exponentially (4.6 to 100 g) between day 40 and 100 of gestation. Similarly, the ratio of placental to foetal weight is also greater in the second trimester (1:1) than in the last trimester (1:10; Robinson et al 1999). These data suggest that the growth rate of the placenta may be more sensitive than the foetus to alterations in nutrition during mid pregnancy (McCrabb et al 1986; 1991; Wallace et al 1999). Of 16 experiments comparing under–nourished to highly–nourished ewes in the second trimester, 14 (87%) reported  effects on placental weight of which high nutrition increased placental size in 9 and decreased it in 3 of such studies (Kelly 1992). Such rapid growth requires a high input of ATP to fuel cell metabolism and function. In vitro studies have found that glucose uptake during this period was greater compared to the first and final trimesters (Pörtner 2009).  

The timing of nutritional restriction within the second trimester determines whether the restriction will affect foetal or placental growth. A 28-day restriction period commencing on day 75 of gestation will affect placental growth since the placenta continues to grow rapidly between day 80 and 100 whereas restriction from day 95 will result in direct effects only on foetal growth (Ehrhardt and Bell 1995; Wallace et al 1999). Imposition of under–nutrition between day 90 and 118 of gestation did not therefore result in any adverse effects on birth weight (Holst and Allen 1992). Moderate under–nutrition resulting in a loss of 0.5 body condition score in the second trimester meant to stimulate placental function through increased blood flow followed by a restoration of maternal requirements in the third trimester increased lamb birth weight both in tropical (Addah and Karikari 2008) and temperate (Holst and Allan 1992; Wallace et al 2002) ewes. This supposition is however true only for adolescent ewes in good body condition otherwise there is the opposite effect for those in poor condition (Robinson et al 1999).  

Two main hypotheses may explain this phenomenon; in adolescent growing ewes, the efficiency of ME use for conceptus growth is lower (0.1–0.15) compared to that for maternal growth and fattening (0.3–0.8) due to high heat increment of pregnancy. Partitioning of this heat indicates that the foetus’s contribution is generally far less than that of utero–placenta in both the first and second trimesters of pregnancy (Figure 4; Robinson and Symounds 1995). Secondly, a moderate degree of restriction of dietary ME intake during the second trimester has been shown to stimulate placental nutrient and oxygen uptake and increased blood flow rate leading to greater foetal growth rate if full nutrient supply is restored in the third trimester. However, placentome number and weight are reduced when ewes are well–nourished (Robinson et al 1999; Metcalfe et al 1988). Similarly, when maternal glucose concentration increases in the rapidly growing over–nourished ewe, placental glucose receptor proteins (GLUT 1 and 3) become insensitive leading to restricted utero–placental blood flow and transport of oxygen, glucose and amino acids to the foetus as well as  reduced placental lactogen secretion (Wallace et al 2004). These result in a decreased demand on the maternal glucose pool which in turn leads to increased glucose utilization by the maternal tissues at the expense of the gravid uterus. The ultimate result of this phenomenon is increased maternal growth rate, fat deposition, high body condition score, reduction in placental mass and lower birth weight of lambs (Wallace et al 1997; 2004). Similar regimes however failed to stimulate consistent placental growth and function in adult primiparous ewes (Wallace et al 1997; 2003).  


Figure 4. Heat increment of pregnancy during different trimesters of preganacy (Data from: Robinson and Symounds 1995)

Given the rapid growth of the placenta and other products of conception during the second trimester, it appears logical to suggest that glucose, because of its higher yield of ATP, is the most important maternal metabolite for foetal growth (Mellor 1983) yet maternal plasma glucose concentration and partitioning has been shown not to affect foetal growth when the level of feeding was restricted in the first and second trimesters of pregnancy (McCrabb et al 1991).


The ovine foetus also has a relatively high demand for amino acid nitrogen in mid than in late pregnancy, averaging about 18 mg/day/g DM of foetus during mid pregnancy and only 4.6 mg/day/g DM during the last trimester (Robinson et al 1999). The inability to meet its energy requirement in mid pregnancy from maternal sources only, often triggers a glucogenic response from the foetal liver and kidneys for the biosynthesis of glutamate, an energy metabolite of amino acid metabolism as an alternative fuel for foetal growth (Bell et al 1989; Neu 2001; Battaglia 2000; Brosnan 2000; Figure 3). An efflux of glutamate from foetal skeletal muscle also contributes to this foetal glutamate pool in the adaptation of the foetus to maternal under–nutrition (Cetin 2001). The role of amino acids gluconeogenesis in the generation of energy during periods of nutritional stress suggest that amino acid supply to the maternal tissues during the second trimester of pregnancy may be more important than ME in alleviating the adverse effects of under–nutrition on lamb birth weight (Lippert et al 1983). The question of which nutrient is most critical in the second trimester has not thus been adequately answered yet. The severity of under–nutrition imposed during pregnancy is dependent on the ability of maternal reserves to adequately offset the impact without jeopardizing the life of the mother. For ewes in good body condition (score = 3.0), a moderate level of under–nutrition in mid pregnancy followed by a restoration of nutrient requirements in the last 15 weeks before parturition leads to maximum birth weight (Wilkinson and Chesnutt 1988; Addah and Karikari 2008). Pre–weaning survival rates and weaning weights of lambs born of ewes whose intake was restricted in the second trimester of pregnancy were similar to those of unrestricted ewes (Holst and Allan 1992). Although low–level feeding (70% of requirements) of ewes during the first 100 day of gestation had no detrimental effects on the carcass or muscle fibre characteristics of their lambs at slaughter, it resulted in lambs with heavier semitendinosus muscle weights, larger muscle fibre diameters and shorter sarcomere lengths than in lambs from adequately fed ewes (Nordby et al 1987). 

When dietary intake of pregnant WAD ewes was restricted in either the first, second or third trimester of pregnancy or unrestricted throughout pregnancy, gross maternal weight gains were greater for ewes supplemented throughout gestation, however, these ewes did not give birth to heavier lambs, rather those restricted in the second trimester had highest placental and birth weights (Addah et al 2007; Addah and Karikari 2008; Figure 2). It was also observed that lambs born of ewes whose intake was restricted in the second trimester had superior pre–weaning average daily gain and survivability than those well–fed throughout pregnancy or restricted in the first or third trimesters of pregnancy (Addah et al 2004). This may be explained by higher initial yield, increased nutrient and IgG content of colostrum in ewes whose intake was restricted in the second trimester (Wallace et al 2001; 2004).


The influence of moderate maternal under–nutrition on placental function and its subsequent effect on lamb birth weight appears to be manifested between the first and second trimesters or before the end of the second trimester only and does not affect lamb birth in the third trimester (Wallace et al 1999) when placental DNA and mass has reached a plateau (Ehrhardt and Bell 1995). Under–nutrition in the second trimester did not also affect the weight of individual foetal organs or whole–body foetal weight (McCrabb et al 1991). Maternal adaptation through tissue mobilization and shifts in nutrient partitioning in favour of the foetus has been widely postulated to explain the phenomenon (Robinson et al 1999).  

Wallace et al (2004) attributed the major limitations to foetal growth in rapidly growing adolescent ewes to the smaller size of the placenta rather than to alterations in its nutrient metabolism or transport capacity. Evidence showing that placental function as opposed to placental size in determining foetal growth  was demonstrated in a study in which the nutrient transport capacity of small placentae of unrestricted ewes were similar to large placentae of restricted ewes (McCrabb et al 1991).


A 15% reduction in nutrient intake during the first 70 days followed by  restoration of recommended daily intake up to day 130 of gestation resulted in a significant alteration in placental morphology in the form of increased growth of the foetal side of the placenta (type D; Figure 1) without affecting foetal size, suggesting placental adaptations to under–nutrition in the second trimester in the form of gross morphological alterations may preserve foetal growth if maternal under–nutrition is not very severe (Steyn et al 2001). Recent studies of the effects of maternal environment on lamb birth weight, however found that maternal energy intake from first to second trimester had little influence on lamb birth weight but intake during the third trimester was positively associated with weight at birth (Gardner et al 2007; Morrison 2008). 

Effects of under–nutrition on intrauterine growth during the third trimester

The third trimester represents the period during which under–nutrition has its greatest effect on production through its effects on udder development, lactational and colostrum yield, development of maternal instincts, and weight and vigour of lambs at birth (Russel 1984). This period of pregnancy is particularly important because approximately 75–80% of foetal growth occurs during the last trimester of pregnancy while feed intake around this time is constrained by reduced volume of the gastrointestinal tract. This is also the period when protein requirement is greatest; approximately 33% greater than the requirement in mid pregnancy (Schloesser et al 1993). Paradoxically a restriction of placental and foetal amino acid supply in the last trimester of pregnancy often results in an efflux of amino acids from the foetus to placenta (Robinson 1999; Owens 1995; Cetin 2001) further demonstrating the nutritional priority of the placenta over the foetus  during periods of nutritional stress. However, this should not be confused with the placental glutamate–glutamine shuttle and amino acid transamination (Figure 1) orchestrated by the foetus itself in periods of nutritional inadequacy.  

In normal feeding management programmes, the nutritional requirement of sheep during pregnancy is often determined based on linear changes in body weight as the conceptus and its associated products increase in weight, however, placental growth is not linearly related to foetal nutrient requirements or growth (Erhardt and Bell 1995) given that moderate nutrient restriction may stimulate placental and lamb growth (Wallace et al 2001; 2004). Earlier studies had demonstrated that the rate at which glucose was partitioned to the foetus in under–nourished and optimally–nourished ewes during the third trimester was similar (McCrabb et al 1991). It was therefore hypothesized that the effects of maternoplacental nutrient restriction on foetal growth are insignificant and the factors regulating the rate of foetal growth during the third trimester originate from sources other than the placenta alone (McCrabb et al 1999).

According to Adu and Olaloku (1979), an average WAD ewe of about 17.5 kg requires 3 MJ ME for maternal maintenance plus 1.5 MJ ME/kg foetus. They reported that a 33% reduction of the full energy requirement of the WAD ewe reduces birth weight by 15%.  Even though the third trimester represents the period of rapid foetal growth, pregnant ewes may lose weight during this period if attention is not paid to maintenance of body condition.  

Malnutrition of the ewe also results in the production of ketone bodies as a consequence of reduced plasma glucose. A 62% increase in plasma ketones during the third trimester of pregnancy reduced the birth weight of WAD lambs by ~37% (Adu and Olaloku 1979). But when plasma glucose concentration was reduced by 58% due to under–nutrition during the last 4 weeks of pregnancy, no effect on lamb birth weight was observed in European ewes (Robinson et al 1999). Based on the relationship between maternal plasma ketone concentration in third trimester and lamb birth weight in European and WAD under–nourished ewes, it has also been found that under–nutrition may have a greater effect on birth weight of WAD lambs than those of European origin (Adu and Olaloku 1979). 

Russel (1984) has recommended a feeding practice of achieving a compromise between meeting the nutrient requirements in full, which is generally unnecessary and uneconomical and a higher degree of under–nutrition which seriously depresses ewe productivity in the third trimester of pregnancy. Another maternal adaptation to under–nutrition in the third trimester is increasing the proximity of nutrients to the foetus through increasing the concentration of nutrients in visceral organs at the expense of the skeletal muscles (Robinson et al 1999). 

Moderate maternal under–nutrition throughout pregnancy may also stimulate placental growth, increase weight of lambs at birth and decrease colostrum yield, and is associated with higher incidence of spontaneous abortions in adolescent ewes (Wallace at al 2001). Higher mortality in lambs born of over–nourished ewes has been attributed to lower intake of colostrum. This is probably because colostrum of over–nourished adolescent ewes has lower energy content compared to moderately under–nourished ewes due to lower concentration of crude protein, lactose and butterfat (Wallace et al 2001). However, in adult ewes, under–nutrition in late pregnancy is reported to have adverse long–term effects on pre–weaning lamb growth rate and mortality as milk production in subsequent lactations decrease compared to ewes which were adequately nourished (McDonald et al 1995). The effects of under–nutrition on peri–natal lamb mortality are difficult to determine as loss of immunity predisposes lambs to diseases. Consequently, diseases and parasites have often been reported as the main cause of early post–natal deaths in WAD lambs in Africa (Abassa 1995).  

Effects of environment on intrauterine growth restriction

Oxygen, glucose, lactate and amino acids are the main substrates that fuel foetal growth. Lower atmospheric oxygen concentration and pressure at higher altitudes results in insufficient concentration of oxygen reaching the maternofoetal tissues via blood circulation (hypoxia).  Hypoxia is therefore expected to directly influence maternofoetal nutrition and has been found to be the main cause of lower birth weights in women living at higher (>2500 m) altitudes (Moore et al 2004). Gestation length and placental weight increased and birth weight decreased by 26–29%  in Chilean native ewes kept at higher altitude compared to those kept at sea level (Parraguez et al 2005). In sheep, the foetus adapts to chronic hypoxia by increasing its ability to acquire and transport oxygen but this compensation is not sufficient to prevent foetal growth retardation or changes to the pattern of tissue growth in ewes chronically exposed to higher altitudes, thereby resulting in reduction in foetal body weight (Jacobs et al 1988). This decline is mainly due to slowing of foetal growth rate in the third trimester (Moore et al 2004). However, in some studies, utero–placental oxygen content and delivery decreased initially in chronically hypoxemic pregnant ewes but this was restored to normal levels after 3 d and the general effects of hypoxia were found to be minor and similar between pregnant and non pregnant ewes (Kitanaka et al 1989). From the above, it appears there is no general trend in the effects of higher altitude on foetal growth. This may be due to differences in genetic and maternal adaptation to altitude–associated IUGR as observed in humans (Moore et al 2004). 

Moderate levels of heat stress have also been shown to decrease placental and foetal weights by 139% and 89% respectively (Wallace et al 2002). In most arid regions of Africa, the effect of hypoxia on foetal growth may be confounded by seasonal variation in temperature which can have detrimental effects on reproductive performance of the ewe through its direct effects on embryo mortality and restricted foetal growth, and indirectly through its impact on availability of feed especially in extensively raised flocks. Foetal losses in the form of abortions and stillbirths are therefore major causes of reproductive losses in most arid areas of Africa. Nearly 50% of all abortions in Burkina Faso and 75% in Niger occur during or towards the end of the hot dry season (Abassa 1995).



Original research cited by the authors in this review was funded by the World Bank through the Agricultural Sub–sector Investment Project (AgSSIP) of the Council for Scientific and Industrial Research, Ghana. We also acknowledge original data from other authors that have been used in the review. 


Abassa K P 1995 Reproductive losses in small ruminants in sub–Saharan Africa: A review. International Livestock Centre for Africa (ILCA). Addis Ababa, Ethopia.

Addah W 2004  Effects of under-nutrition during pregnancy on the reproductive performance of Djallonke ewes. MSc thesis. Department of Animal Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Addah W and Karikari P K 2008 Effects of dietary restrictions during different stages of pregnancy on differential plasma protein concentration, placental and birth weights of adolescent Djallonké sheep. Livest. Res. Rural Devt. 20 (#147).

Addah W, Karikari P K, Osafo E L K, Oppong-Anane K, Teye G A 2007 Effects of undernutrition during pregnancy on the relationship between maternal plasma metabolites concentration and lamb birth weight of adolescent Djallonké sheep. Ghanaian J. Anim. Sci. 2:184–195.

Adu I F and Olaloku E A 1979 A note on nutrition during late pregnancy in West African Dwarf sheep. Brit. J. Anim. Prod. 28:123– 126.

Battaglia F C and Meschia G 1986 An introduction to fetal physiology. Academic press, Orlando, FL. p. 100.

Battaglia C 2000 Glutamine and glutamate exchange between the fetal liver and the placenta. J. Nutr. 130: 974S–977S.

Bauer M K, Harding J E,  Bassett N S, Breier B H,  Oliver M H, Gallaher B H,  Evans P C, Woodall S M and Gluckman P D 1998 Fetal growth and placental function. Mol. Cell. Endocrinol. 140: 115–120.

Bell  A W, Kennaugh J G, Battaglia F C  and Meschia G 1989 Uptake of amino acids and ammonia at mid–gestation by fetal lamb. Quarterly J. Exp. Physiol. 74:635 – 643.

Bell A W and Bauman D E 1997 Adaptations of glucose metabolism during pregnancy and lactation.  J. Mammary Gland Biol. Neoplasia 2:265–278

Bell A W, Kennaugh J M, Battaglia F C, Makowski E L, Meschia G 1986 Metabolic and circulatory studies of foetal lambs at mid gestation. Am. J. Physiol. 250: E538–E544.

Borowczyk E, Caton J S, Redmer D A, Bilski J J, Weigl R M, Vonnahme K A, Borrowicz P P, Kirsch J D, Kraft K C, Reynolds L P and Grazul-Bilska A T 2006 Effects of plane of nutrition and early embryonic development in sheep. J. Anim. Sci. 84: 1593–1599.

Brockman R P 1993 Glucose and short-chain fatty acid metabolism. In Forbes JM, France J (eds.). Quantitative aspects of ruminant digestion and metabolism, CAB International, Wallingford, UK, pp. 247265.

Brosnan J T 2000 Glutamate, at the interface between amino acid and carbohydrate metabolism. J. Nutr. 130: 98859905.

Cetin I 2001 Amino acid interconversion in the fetal placental unit: the animal model and human studies in vitro Pediatr. Res. 49: 148–154.

Costello P M, Rowlerson A, Astaman N A, Anthony F E W, Sayer A A, Cooper C, Hanson M A and Green L R 2008 Peri–implantation and late gestation maternal under–nutrition differentially affect fetal sheep skeletal muscle. J. Physiol. 2371–2379.

Ehrhardt R A and Bell A W 1995 Growth and metabolism of the ovine placenta mid–gestation. Placenta 16: 727–741.

Elrod C C, Van Amburgh M and Butter W R 1993 Alterations of pH in response to dietary protein in cattle are unique to uterus. Brit. J. of Anim. Sci. 71: 702–706.

Fowden A L, Ward J W, Wooding F P B, Forhead A J and Constancia M 2006 Programming placental nutrient transfer capacity. J. Physiol. 572: 5–15.

Gardner D S, Buttery P J, Daniel Z and Symonds M E 2007 Factors affecting birth weight in sheep: maternal environment. Reproduction 133: 297–307.

Greenwood P L, Hearnshaw H, Cafe L M, Hennessy D W and Harper G S 2004 Nutrition in utero and pre–weaning has longterm consequences for growth and size of piedmontese and Wagyu–sired steers. J. Anim. Sci. 82(suppl.1):722.

Hammer C J, Thorson J F, Meyer A M, Redmer D A, Luther J S, Neville T L, Reed J J, Reynolds L P, Caton J S and Vonnahme K A 2011 Effects of maternal selenium and plane of nutrition during gestation on passive immunity and health in neonate lambs. J. Anim. J Anim Sci. 89: 36903698.

Harding J, Lui L, Evans P, Oliver M and Gluckman P 1992 Intrauterine feeding of the growth retarded fetus: can we help? Early human Dev. 29:193–197.

Harding J E and Johnston B M 1995 Nutrition and fetal growth. Reprod. Fertil. Dev. 7: 539–547.

Hausman G J 2009 Programming of fetal fat and muscle: Natural and genetic fetal restriction and exogenous nutritional influences (abstract). J. Anim. Sci. 87 (E–Suppl.): 2/J.

Holst P J and Allan C J 1992 Timing of moderate nutritional restriction in mid pregnancy and its effects on lamb birth weight and ewe gestation. Aust. J. Exp. Agric. 32: 11–14.

Jacobs R, Robinson J S, Owens J A, Falconer J and Webster M E 1988 The effect of prolonged hypobaric hypoxia on growth of fetal sheep. J. Dev. Physiol. 10:97–112.

Kelly R W 1992 Nutrition and placental development. Proc. of Nutrition Society of Australia 17: 203–211.

Kitanaka T, Gilbert R D, Longo L D 1989 Maternal responses to long–term hypoxemia in sheep. J. Physiol. 256: R1340–R137.

Leiser R, Kreb C, Ebert B and Dantzer V 1997 Placental vascular corrosion cast studies: a comparison between ruminants and humans. Micr. Res. Tech. 38:76–78.

Lippert M, Milne J A and  Russel A J F 1983 Effects of mid – pregnancy supplementation on hill–ewe performance. Brit. J. of Anim. Prod. 36:543 (abstr.).

Loveridge N, Caple I W, Rodda C, Martin T J and Care A D 1988 Further evidence for a parathyroid hormone–related protein in fetal parathyroid glands of sheep. Quarterly J. Exp. Physiol. 73: 781784

McCrabb G J, Egan A R and Hosking B J 1991 Maternal under–nutrition during mid pregnancy in sheep. Placental size and its relationship to calcium transfer during late pregnancy. Brit. J. Nutr. 65: 157–168.

McCrabb G J, Hosking B J and  Egan A R 1986 Placental size and foetal growth in relation to maternal undernutrition during mid–pregnancy. Proc. of the Nutrition Society of Australia 11:147.

McDonald P, Edwards R A, Greenhalgh J F D and Morgan C A 1995 Animal Nutrition, 5th edition. Addison Wesley, Longman Ltd. Edinburgh, UK. pp. 514–516.

Mellor D J 1983 Nutritional and placental determinants of foetal growth rate in sheep and consequences for the newborn lambs. Brit. Vet. J. 139:307–324.

Metcalfe J, Stock M K and Barron D H 1988 Maternal physiology during gestation. In: Knobil E, Neill J, Ewing LL, Greenwald GS, Markert CL, Pfaff EW (eds.). The physiology of reproduction. Raven Press, New York.  pp. 2145–2176.

Moore L G, Shriver M, Bemis L, Hickler B, Wilson M, Brutsaert T, Parra E and Vargas E 2004 Maternal adaptation to high–altitude pregnancy: An experiment of nature–Review. Placenta 25: S60–S71.

Morrison J L 2008 Sheep models of intrauterine growth restriction: fetal adaptations and consequences (review). Clin. Expert. Pharmacol. Physiol. 35:730–743.

Narkewicz M R, Thureen P J, Sauls S D, Tjoa S, Nikolayevsky N and Fennessey P V 1996 Serine and glycine metabolism in hepatocytes from mid gestation fetal lambs.  Pediatr. Res. 39:1085–1090.

Neu J 2001 Glutamine in the fetus and critically ill low birth weight neonate: metabolism and mechanism of action. J. Nutr. 131: 2585S2589S.

Nordby D J, Field R A, Riley M L and Kercher C J  1987 Effects of maternal under–nutrition during early pregnancy on growth, muscle cellularity, fibre type and carcass composition in lambs. J. of Anim. Sci. 64: 1419–1427.

O`Callaghan D and Boland M P 1999 Nutritional effects on ovulation, embryo development and the establishment of pregnancy in ruminants. Brit. J. of Anim. Sci. 68: 299–314.

O`Doherty J V and Crosby T F 1998 Blood metabolite concentrations in late pregnant ewes as indicators of nutritional status. Brit. J. of Anim. Sci. 66:675–683.

Orr R J and Treacher T T 1994 The effect of concentrate level on the intake of grass silages by ewes in late pregnancy. Anim. Prod. 58: 109–116.

Osgerby J C, Wathes D C, Howward D and Gadd T S 2002 The effect of under–nutrition on ovine fetal growth. J. Endocrinol. 173: 131–141.

Owens J A 1991 Endocrine and substrate control of foetal growth: Placental and Maternal influences and insulin–like growth factors. Reprod. Fertil. Dev. 3: 501–517.

Parraguez V P, Atlagich M, Diaz R, Bruzzone M E, Behn C and Raggi L 2005 Effect of hypobaric hypoxia on lamb intrauterine growth: comparison between high– and low–altitude native ewes. Reprod. Fertil. Dev. 17:497–505.

Pörtner R 2009 Characteristics of mammalian cells and requirements for cultivation. In:. Eibl R, Eibl D, Pörtner R, Catapano G, Czermak P (eds.) Cell and tissue reaction engineering: principles and practice Springer – Verlag Berlin Heidelberg. pp. 13–53.

Robinson J J 1990 Nutrition in reproduction of farm animals. Nutr. Res. Rev. 3: 253–276.

Robinson J J, Rooke J A and McEvoy T G 2002 Sheep nutrition. Freer M, Dove H. (eds). CAB International. pp 189–211.

Robinson J J, Sinclair K D and McEvoy T G 1999 Nutritional effects on foetal growth. Brit. J. Anim. Sci. 68: 315–332.

Robinson J J and Symonds M E 1995 Whole–body fuel selection: “Reproduction”. Proc. of the Nutritional Society 54: 283–299.

Russel A J F 1984 Means of assessing the adequacy of nutrition of pregnant ewes. Livest. Prod. Sci. 11: 429–436.

Schloesser B J, Thomas V M, Petersen M K, Kott R W and Hatfield P G 1993 Effects of supplemental protein source on passage of nitrogen to the small intestine, nutritional status of pregnant ewes and wool follicle development of progeny. J. Anim. Sci. 71: 1019–1025.

Steyn C, Hawkins P, Saito T, Noakes D E, Kingdom J C P and Hanson M A 2001 Undernutrition during the first half of gestation increases the predominance of fetal tissue in late–gestation ovine placentomes. European J. Obstetrics Gynecol. Reprod. Biol. 98: 165–170.

Tuah A K and Klusey W 1992 The effect of pregnancy on the level of various blood constituents in sheep. Proc. of the 13th Ghanaian Anim. Sci. Assoc. Symp., Kumasi, Ghana.

Vatnick I, Schoknecht P A, Darrigrand R and Bell A W 1991 Growth and metabolism of the placenta after unilateral fetectomy in twin–pregnant ewes. J. Dev. Physiol. 15: 351–3561.  

Vonnahme K A 2007 Nutrition during gestation and fetal programming. Proc. The Range Beef Cow Symp. XX. Dec. 11–13, 2007. 10 pp. Fort Collins, Colarado, USA

Wallace J M, Aitken R P and Cheney M A 1999 Switching maternal dietary intake at the end of the first trimester has profound effects on placental development and fetal growth in adolescent ewes carrying singleton fetuses. Biol. Reprod. 61:101–110.

Wallace J M, Aitken R P and Cheney M A 1996 Nutrient partitioning and foetal growth in rapidly growing adolescent ewes. J. Reprod. Fertil. 107:183–190.

Wallace J M, Aitken R P, Milne J S and William W 2004 Nutritionally mediated  placental growth restriction in the growing adolescent: consequence for the fetus. Biol. Reprod. 71: 1055–1062

Wallace J M, Bourke D, Da Silva D and Aitken R P 2001 Nutrient partitioning during adolescent pregnancy. Reproduction 122: 347–357.

Wallace J M, Bourke D A, Aitken R P, Leitch N and Hay Jr. W W 2002. Blood flow and nutrient uptakes in growth restricted pregnancies induced by overnourishing adolescent sheep. Am J Physiol. Regul. Integr. Comp. Physiol. 282: R1027–R1036.

Wallace J M, Da Silva P, Aitken R P and Cruickshank  M A 1997 Maternal endocrine status in relation to pregnancy outcome in rapidly growing adolescent sheep. J. Endocrinol. 155: 359–368.

Wallace J M, Milne J S, Leitch N and Aitken R P 2003 Overnourishing singleton bearing adult ewes stimulates adiposity but does not influence nutrient partitioning to the gravid uterus. Pediatr. Res. 6(part 2, suppl): 38A–38A.

Wilkinson S C and Chestnutt D M B 1988 Effects of level of food intake in mid and late pregnancy on the performance of breeding ewes. Anim. Prod. 47: 411–419.

Received 29 June 2012; Accepted 8 August 2012; Published 3 September 2012

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