J. Anim Sci. 2006. 84:3451-3459. doi:10.2527/jas.2006-132
© 2006 American Society of Animal Science
Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions1
K. A. Vonnahme*,2,
B. W. Hess*,
,
M. J. Nijland*,,
P. W. Nathanielsz*,
and
S. P. Ford*,,3
* The Center for the Study of Fetal Programming, Laramie, WY 82071;
and
Department of Animal Science, University of Wyoming, Laramie 82071;
and
Department of Obstetrics and Gynecology, University of Texas Health Sciences Center, San Antonio 78229
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Abstract
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Maternal nutrient restriction from early to midgestation can lead to fetal growth retardation, with long-term impacts on offspring growth, physiology, and metabolism. We hypothesized that ewes from flocks managed under markedly different environmental conditions and levels of nutrition might differ in their ability to protect their own fetus from a bout of maternal nutrient restriction. We utilized multiparous ewes of similar breeding, age, and parity from 2 flocks managed as 1) ewes adapted to a nomadic existence and year-long, limited nutrition near Baggs, WY (Baggs ewes), and 2) University of Wyoming ewes with a sedentary lifestyle and continuous provision of more than adequate nutrition (UW ewes). Groups of Baggs ewes and UW ewes were fed 50 (nutrient restricted) or 100% (control fed) of National Research Council recommendations from d 28 to 78 of gestation, then necropsied, and fetal and placental data were obtained. Although there was a marked decrease (P < 0.05) in fetal weight and blood glucose concentrations in nutrient-restricted vs. control fed UW ewes, there was no difference in these fetal measurements between nutrient-restricted and control-fed Baggs ewes. Nutrient-restricted and control-fed UW ewes exhibited predominantly type A placentomes on d 78, but there were fewer (P c0.05) type A and greater (P < 0.05) numbers of type B, C, and D placentomes in nutrient-restricted than control-fed Baggs ewes. Placental efficiency (fetal weight/placentomal weight) was reduced (P = 0.04) in d 78 nutrient-restricted UW ewes when compared with control-fed UW ewes. In contrast, nutrient-restricted and control-fed Baggs ewes exhibited similar placental efficiencies on d 78. This is the first report of different placental responses to a nutritional challenge during pregnancy when ewes were selected under different management systems. These data are consistent with the concept that Baggs ewes or their conceptuses, which were adapted to both harsh environments and limited nutrition, initiated conversion of type A placentomes to other placentomal types when subjected to an early to mid-gestational nutrient restriction, whereas this conversion failed to occur in UW ewes. This early placentomal conversion in the Baggs ewes may function to maintain normal nutrient delivery to their developing fetuses during maternal nutrient restriction.
Key Words: fetal growth • gestational nutrient restriction • placentomal conversion • sheep
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INTRODUCTION
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Rangelands of the High Plains and Intermountain West of the United States experience yearly fluctuation in quality and quantity of forages (Anderson, 1993
; DelCurto et al., 1999; DelCurto et al., 2000). Paterson et al. (2002) reported that forage digestibility of Montana pastures declined from May to September. Because of low protein and high fiber content of poor quality forages, livestock consumption of forages may decline (Krysl and Hess, 1993). Pregnant ewes on rangeland with no supplementation often experience bouts of nutrient restriction of less than 50% of National Research Council (NRC, 1985) recommendations during early gestation (Thomas and Kott, 1995).
The fetal origins hypothesis proposes that alterations in fetal nutrition during critical periods of gestation can affect growth, physiology, and metabolism of offspring in postnatal life (Barker and Clark, 1997; Hawkins et al., 1997; McMillen et al., 2001). Impacts of nutrient restriction during the first half of gestation in ewes include reduced fetal growth (Vonnahme et al., 2003), poor wool and carcass quality (Black, 1983; Bell, 1992; Kelley et al., 1996), and increased blood pressure and reduced kidney glomerulus number (Gilbert et al., 2005) of their offspring.
Factors that influence placental growth and vascular development affect fetal growth and thus fetal and neonatal mortality and morbidity (Mellor, 1983; Reynolds and Redmer, 1995; Torry et al., 2004). In sheep, cotyledons on the chorioallantoic membrane attach by finger-like projections to discrete caruncles on the uterine wall (see Ford, 2000, for review). The cotyledonarycaruncular unit (placentome) is the area of hemotrophic, as opposed to histotrophic, nutrient, and waste product exchange between the mother and fetus.
This study compared the effects of early to midgestational nutrient restriction on maternal and fetal weights and blood glucose concentrations, as well as placentomal growth and differentiation, in ewes derived from 2 flocks selected under markedly different production environments and nutrient availabilities.
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MATERIALS AND METHODS
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Animals
All animal procedures were approved by the University of Wyoming Animal Care and Use Committee. Ewes of similar age (4- to 5-yr-old) and parity (2 to 3) were obtained from 2 flocks of Rambouillet/Columbia cross ewes. The first flock located near Baggs, Wyoming (Baggs ewes) was adapted over approximately 30 yr to a nomadic existence, traveling approximately 402 km/yr to graze a land mass that ranged from desert terrain (annual rainfall 18 to 23 cm; Ostresh et al., 1990) to high mountain pastures with limited nutritional supplementation. The second flock was also maintained for approximately 30 yr by the University of Wyoming (UW ewes), and in contrast to the Baggs ewes, had a relatively sedentary lifestyle and consumed a diet from birth that always met or exceeded NRC recommendations.
For 1 mo before breeding, Baggs and UW ewes were maintained in separate, group pens in an open-fronted pole barn located at the Animal Science Livestock Center in Laramie, Wyoming. Beginning on September 1, 2004, all ewes were observed for estrus twice daily and bred to the same intact ram (Rambouillet/Columbia cross) at first exhibition of estrus and 12 h later (first day of mating = d 0). Animals were fed alfalfa hay at 2% of BW from 30 d before mating to d 20 postmating. A BCS of 1 (emaciated) to 9 (obese) was assigned by 2 trained observers after palpation of the transverse and vertical processes of the lumbar vertebrae (L2 through L5) and the region around the tail head (Sanson et al., 1993). Sanson et al. (1993) demonstrated that BCS is highly related to carcass lipids and can be used to estimate energy reserves available to ewes. On d 20 post-mating, 40 Baggs ewes and 37 UW ewes were weighed and body condition scored, and then placed in an indoor facility in individual pens containing feeders and waterers. The diet consisted of a pelleted beet pulp and a mineral-vitamin mixture as previously described (Vonnahme et al., 2003). Rations were delivered on a DM basis to meet the TDN required for an early pregnant ewe (NRC, 1985). Individual diets were calculated on a metabolic BW basis (BW0.75).
On d 28, ewes within the UW or Baggs flocks were paired by BW and BCS, and 1 member of each pair was assigned to a control-fed group (100% NRC recommendations); the other member of each pair was assigned to a nutrient-restricted group, which received 50% of the pelleted beet pulp and mineral-vitamin mixture provided to the control-fed group. Beginning on d 28 of gestation, and continuing at 7-d intervals, all ewes were weighed and their rations were individually adjusted up for BW gain or down for BW loss. Body condition scores were obtained again on d 49 of gestation and again on the day of necropsy (d 78 of gestation). On approximately d 45, pregnancy was confirmed and the number of fetuses carried by each ewe was determined by ultrasonography (Ausonics Microimager 1000 sector scanning instrument, Ausonics Pty. Ltd., Sydney, Australia). A subset of ewes in each group carrying singleton and twin fetuses was selected to be necropsied on d 78 of gestation, and included 13 control-fed UW ewes (7 singleton and 6 twin pregnancies), 10 nutrient-restricted UW ewes (6 singleton and 4 twin pregnancies), 10 control-fed Baggs ewes (5 singleton and 5 twin pregnancies), and 8 nutrient-restricted Baggs ewes (4 singleton and 4 twin pregnancies). Beginning on d 79, the remainder of the nutrient-restricted ewes in each group was realimented to 100% of NRC requirements until delivery and allowed to lamb.
Immediately before necropsy, each ewe was weighed and a blood sample was collected via jugular venipuncture into a 10-mL heparinized vacuum tube containing 2.5 mg of sodium fluoride per mL of blood (Sigma, St. Louis, MO) for glucose determination. Ewes were then given an overdose of sodium pentabarbitol (Abbott Laboratories, Abbott Park, IL) and exsanguinated, and the gravid uterus was carefully opened to expose the umbilical cord of each fetus. Umbilical venous blood was then collected into a heparinized vacuum tube containing 2.5 mg of sodium fluoride per mL of blood, as previously described for maternal blood. Tubes containing maternal and umbilical blood were cooled on ice and then centrifuged at 3,000 x g for 10 min and stored at –80°C until analyzed for glucose. After removing the fetus(es) from the gravid uterus, weight(s) and crown-rump length(s) (CRL) were recorded. Crown-rump length was measured with a cloth tape measure as the distance from the crown of the skull to the base of the tail. The fetal heart was removed, and the weights of right and left ventricular walls were recorded, as previously described (Vonnahme et al., 2003).
Placentomal Evaluation
Each placentome was dissected from the uterine wall, weighed, and its morphologic type was recorded (Figure 1). Morphologic type was based on the classification scheme of Vatnick et al. (1991) and was based on the placentome appearance, as follows: 1) caruncular tissue completely surrounding the cotyledonary tissue (type A), 2) cotyledonary tissue beginning to grow over the surrounding caruncular tissue (type B), 3) flat placentomes with cotyledonary tissue on 1 surface and caruncular tissue on the other (type C), and 4) everted placentomes resembling bovine placentomes (type D). All placentomes were pooled to determine total placentomal weight.
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Figure 1. Placentomal types (types A, B, C, and D) recovered from a single, d 78, nutrient-restricted Baggs, WY (Baggs) ewe, carrying a singleton fetus. Arrows depict cotyledonary (COT) and caruncular (CAR) tissues.
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Glucose Analysis
Glucose was analyzed using the Infinity colorimetric assay (Cat. # R15498, ThermoTrace Ltd., Melbourne, Australia) modified in the following manner: plasma samples were diluted 1:5 in PBS, and 10 µL of diluted plasma was added to 300 µL of reagent mix. All samples were run in triplicate, and sample analysis was completed using multiple assays. The intra- and interassay CV were 5 and 7%, respectively.
Statistical Analysis
Data were analyzed by ANOVA appropriate for a completely random design having a 2 (ewe type) x 2 (diet) factorial arrangement of treatments. Analyses were completed using the GLM procedure (SAS Inst. Inc., Cary, NC). Model statements included the effects of diet, ewe type, fetal number, and their interactions on fetal weight, fetal CRL, fetal right and left ventricular weight divided by the weight of the fetus, placentomal number, placentomal weight, and percentage of each morphologic type of placentome. Percentage morphological type was calculated by taking the number of each placentomal type (i.e., A, B, C, or D) and dividing by the total number of placentomes for that conceptus. Further, the model statements included effects of diet and ewe type on ewe BCS, percentage BW loss or gain, and eviscerated carcass weight. Because ewe type x diet interactions were detected for some variables (P < 0.05), simple effect means are presented throughout the manuscript, and means were separated using PDIFF of SAS. Data are presented as means ± SEM and are considered different when P < 0.05, unless otherwise stated.
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RESULTS
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Body condition scores of UW and Baggs ewes were similar at d 28 of gestation (Table 1) averaging 5.4 c0.1 overall. The BCS of both control-fed UW and control-fed Baggs ewes remained relatively constant throughout the 50-d experimental period. The BCS of nutrient-restricted UW ewes declined from d 28 to 49 (P = 0.03) and again between d 49 and 78 (P = 0.04). In contrast, the BCS of nutrient-restricted Baggs ewes remained relatively constant between d 28 and 49, before declining by d 78 (P = 0.04). As a result, BCS of nutrient-restricted Baggs ewes were greater (P = 0.03) than those of nutrient-restricted UW ewes on d 78 of gestation.
On d 28 of gestation, whereas there were no BW differences between control-fed and nutrient-restricted UW ewes or between control-fed and nutrient-restricted Baggs ewes, UW ewes were heavier (P = 0.03) than Baggs ewes (93 ± 5 vs. 78 ± 3 kg, respectively). As depicted in Figure 2, both control-fed UW and control-fed Baggs ewes exhibited similar and progressive increases in BW change from d 28 through 78, averaging 7.5 ± 0.6%. In contrast, whereas nutrient-restricted UW and nutrient-restricted Baggs ewes lost BW throughout the 50-d nutrient restriction period, nutrient-restricted UW ewes lost a greater percentage of their d-28 BW than nutrient-restricted Baggs ewes (7.4 c0.4 vs. 4.7 ± 0.5%, respectively, P = 0.03). Nutrient-restricted UW and nutrient-restricted Baggs ewes had lighter eviscerated carcass weights than their control-fed groups (57.4 ± 4.4 vs. 66.0 ± 3.3 kg and 47.1 ± 1.4 vs. 55.2 ± 1.3 kg, respectively; P < 0.01).
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Figure 2. Percentage weight change of Baggs, WY (Baggs) ewes selected to a nomadic lifestyle and limited nutrition and University of Wyoming (UW) ewes selected to a sedentary lifestyle and more than adequate nutrition when fed 100 (control fed) or 50% (nutrient restricted) of NRC (1985) recommendations from d 28 to 78 of gestation.
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Within ewe type (UW or Baggs) and dietary treatment (control fed and nutrient restricted), there was no significant difference in the weight or CRL of singleton and twin fetuses (Table 2). In contrast, fetuses from nutrient-restricted UW ewes were markedly lighter (P = 0.02) than fetuses from control-fed UW ewes. Whereas fetuses from nutrient-restricted UW ewes were also numerically shorter than fetuses from control-fed UW fetuses, only the CRL of twin fetuses reached significance (P < 0.05). No difference in weight or CRL was observed between fetuses from control-fed and nutrient-restricted Baggs ewes. When fetal weight was divided by ewe live weight on d 78 of gestation, control-fed and nutrient-restricted UW ewes averaged 0.32 and 0.26%, respectively, whereas control-fed and nutrient-restricted Baggs ewes averaged 0.32 and 0.38%, respectively.
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Table 2. Fetal measurements for University of Wyoming (UW) ewes and ewes located near Baggs, WY (Baggs) on d 78 of gestation
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When fetal ventricular weight was divided by fetal BW, singleton fetuses from nutrient-restricted UW ewes had greater right ventricular/fetal weight ratios than singleton or twin fetuses from control-fed UW ewes (P < 0.05, Table 2
). Singleton and twin fetuses from nutrient-restricted UW ewes also had greater (P < 0.05) left ventricular weight/fetal weight ratios than fetuses from control-fed UW ewes. There were no differences in right ventricular weight/fetal weight ratios in the fetuses of control-fed and nutrient-restricted Baggs ewes, and increased (P < 0.05) left ventricular/fetal weight ratios were only observed in twin fetuses of nutrient-restricted Baggs ewes when compared with singleton and twin fetuses from control-fed Baggs ewes.
There were no differences in total placentome number per gravid uterus between control-fed and nutrient-restricted UW ewes regardless of whether they were gestating singleton or twin fetuses (Table 2). In contrast, the total placentome number of singleton or twin pregnancies of nutrient-restricted Baggs ewes tended to be reduced when compared with that of singleton or twin pregnancies of control-fed Baggs ewes, but only placentome numbers of singleton pregnancies reached statistical significance (P < 0.05). Total placentome weight per gravid uterus of control-fed UW ewes with twin pregnancies was markedly greater (P = 0.04) than that of singletons, whereas there was no difference in total placentomal weight between singleton and twin pregnancies of nutrient-restricted UW ewes (Table 2). In contrast, total placentome weight per gravid uterus of Baggs ewes with twin pregnancies was greater (P < 0.05) than that of singleton pregnancies regardless of dietary group. Placental efficiency (fetal weight/total placentomal weight) was reduced (P = 0.04) in nutrient-restricted UW ewes when compared with control-fed UW ewes on d 78 (0.37 ± 0.05 vs. 0.53 c0.05) but was similar (P > 0.50) for nutrient-restricted and control-fed Baggs ewes (0.50 ± 0.04 vs. 0.47 ± 0.02, respectively). In singleton and twin pregnancies, placentomal morphology was similar for control-fed and nutrient-restricted UW ewes, which were predominantly type A (Figure 3). In contrast, there was a marked reduction (P < 0.05) in the percentage of type A placentomes and increased percentages of type B, type C, and type D placentomes in singleton and twin-bearing nutrient-restricted Baggs ewes compared with singleton and twin-bearing control-fed Baggs ewes (Figure 3).
On d 78, blood glucose concentration of nutrient-restricted UW ewes and nutrient-restricted Baggs ewes were markedly lower (P < 0.05) than those of control-fed UW ewes and control-fed Baggs ewes (Table 3). Blood glucose concentrations were lower (P = 0.04) in fetuses from control-fed Baggs ewes when compared with those of fetuses from control-fed UW ewes on d 78. Whereas glucose concentrations in fetal blood of nutrient-restricted UW ewes were reduced (P = 0.04) when compared with glucose concentrations in the blood of fetuses from control-fed UW ewes, concentrations of glucose in the blood of fetuses from nutrient-restricted and control-fed Baggs ewes were similar on d 78. No differences were observed between glucose concentration in the blood of singleton and twin fetuses in any dietary group (data not shown).
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Table 3. Maternal and fetal glucose concentration (mg/dL) in University of Wyoming (UW) ewes and ewes located near Baggs, WY (Baggs) on d 78 of gestation
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DISCUSSION
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To our knowledge, this is the first study to demonstrate that the environment, nutrition, or both under which ewes are selected can alter physiological responses to a bout of maternal nutrient restriction. Further, although these ewes were of similar breeding (Rambouillet/Columbia), considerable genetic differences may exist between the UW and Baggs ewes and contribute to the differences observed. Fetal weights were unaffected when Baggs ewes, selected under limited nutritional inputs and harsh environments, were exposed to a bout of nutrient restriction from early to midgestation. In contrast, UW ewes, selected with more than adequate nutrition and optimal environments, experienced a 30% decrease in fetal weight to the same bout of nutrient restriction. In the past few years, several laboratories have evaluated the impact of maternal nutrient restriction from early to midgestation on fetal and placental development in the sheep (Clarke et al., 1998; Osgerby et al., 1999; Vonnahme et al., 2003) and have reported markedly different results. The reasons for these differences may relate to differences in ewe breed, age, or parity but may also relate to differences in nutritional or environmental exposures of their experimental ewes during fetal or postnatal life. An understanding of how the 2 flocks of ewes utilized in this study evolved in approximately 30 yr to be nutrient responsive or nutrient resistant could be critically relevant to our understanding of factors dictating nutrient requirements during gestation.
Buhimschi et al. (2001) reported that the levels of hypertension, intrauterine growth restriction, and fetal death to nitric oxide inhibition during gestation were significantly different in the same strain of rat purchased from different commercial suppliers. They concluded that these differences may represent subtle genetic or environmental differences between the 2 out-bred colonies resulting in dramatic variations in response to nitric oxide inhibition. One difference reported by Buhimschi et al. (2001) of possible relevance to this study was that the diet fed to these 2 colonies differed in relative amounts of several AA, minerals, and vitamins. In this regard, Knight et al. (2005) reported different impacts of a 30% maternal nutrient restriction from d 6.5 to 18.5 of gestation in 2 strains of mice on fetal and placental size and offspring growth. Further, differences in the susceptability of 2 outbred rat strains to 2,3,7,8-teterachlorodibenzo-p-dioxin-induced fetal death and placental dysfunction have been observed, despite the fact that they exhibited identical primary structure of their aryl hydrocarbon receptor (Kawakami et al., 2005). These studies suggest that within or between breed (or strain) differences may exist in the susceptibility of the conceptus to a variety of maternal stressors.
Whereas nutrient-restricted UW and nutrient-restricted Baggs ewes lost BW and BCS throughout the 50-d nutrient restriction period, nutrient-restricted Baggs ewes lost less BW and BCS than nutrient-restricted UW ewes. Although BW of UW ewes were greater than Baggs ewes at the start of the study, this difference appeared to be related to frame size because BCS were similar across the 2 groups. It is speculated that this difference in BW loss during nutrient restriction may be due to the Baggs ewes being more efficient in feed conversion, utilization, or both when compared with UW ewes. An increased efficiency of nutrient delivery to the fetus by nutrient-restricted Baggs ewes when compared with nutrient-restricted UW ewes is also suggested by the differential impacts of a prolonged maternal nutrient restriction on the weights of fetuses recovered on d 78 of gestation. Although fetuses recovered from nutrient-restricted UW ewes were approximately 30% lighter than fetuses recovered from control-fed UW ewes, there were no differences in fetal weight between nutrient-restricted and control-fed Baggs ewes. This ability to maintain fetal size in the face of restricted nutrient supply does not result from differences in the fetal/maternal weight ratio because fetal size on d 78 in control-fed UW and control-fed Baggs ewes was directly proportional to group differences in ewe BW averaging 0.32% of ewe BW in both groups. Because of the marked decrease in fetal weight in the nutrient-restricted UW ewes, the fetal/maternal weight ratio had decreased to 0.26% by d 78, whereas nutrient-restricted Baggs ewes, which exhibited d 78 fetal weights similar to that of their respective controls, averaged 0.38%.
Although major placentomal growth is complete by midgestation (Ehrhardt and Bell, 1995; Reynolds et al., 2005a,b), individual placentomes may undergo morphologic and functional transformations as fetal demand for nutrients increases in the second half of gestation (Hoet and Hanson, 1999; Osgerby et al., 2004). Results from several laboratories demonstrate an increased conversion of type A placentomes to B, C, or D placentomal types in undernourished ewes when compared with their well-fed counterparts; however, this conversion has been thought to occur only in late gestation in association with an exponentially growing fetus (Hoet and Hanson, 1999; Osgerby et al., 2002; Osgerby et al., 2004). Osgerby et al. (2004) reported that the conversion of type A placentomes to more advanced placentomal types was associated with a flattening of the placentome and an increased ratio in the area of interdigitated maternal and fetal villi to unattached fetal allantochorion, which may enhance nutrient delivery to the fetus. This conversion from type A through more advanced placentomal types is also generally associated with an increase in placentomal weight (Ford et al., 2004; Osgerby et al., 2004).
The apparent ability of the nutrient-restricted Baggs ewes to supply the fetus with adequate nutrients for normal growth and development may be facilitated by the early conversion of type A placentomes to more advanced types (B, C, and D). This concept is supported by the observation that the failure of nutrient-restricted UW ewes to convert their type A placentomes to more advanced types was associated with significant fetal growth restriction by d 78 of gestation. Similar to the results obtained with nutrient-restricted UW ewes in our study, Osgerby et al. (2002) reported that a less severe 30% global nutrient restriction from d 26 of gestation in a group of multiparous Welsh mountain ewes, which failed to affect placentomal growth or type by d 90, led to alterations in fetal organ growth. Interestingly, when these researchers allowed a group of these undernourished ewes to gestate their fetuses through d 135 of gestation, they exhibited greater numbers of type C and D placentomes than adequately fed control ewes, but fetal BW and fetal organ weights remained growth retarded. These data are consistent with the concept that early placentomal conversion may be necessary to alleviate the impact of maternal nutrient restriction on the fetus.
Hoet and Hanson (1999) suggested that the advancement in placentomal morphologic type may be associated with a compensatory increase in placentomal vascularization in response to nutrient restriction. Our laboratory has confirmed that as ovine placentomes progress from type A through types B, C, and D, they increase in size and vascularity (Ford et al., 2004), as well as blood flow (Ford et al., 2006). On the basis of a number of studies, increased blood flow at the fetal-maternal interface appears to be a primary determinant of increased transplacental exchange during the later half of gestation in livestock species including the sheep (Ford, 1995; Reynolds and Redmer, 1995; Reynolds et al., 2005a,b). The fact that placentome number was reduced (P < 0.05) in nutrient-restricted Baggs ewes carrying normal weight singleton fetuses and tended to be reduced (P < 0.09) in nutrient-restricted Baggs ewes carrying normal weight twins suggests that the efficiency of individual placentomes must be increased with their conversion of type A placentomes to types B, C, and D. Evidence suggests that placentome number in the sheep is established by d 40 of gestation and remains constant thereafter (Schneider, 1996; Heasman et al., 1999). Further, the fact that both ewe strains had a similar eviscerated BW in response to nutrient restriction on a percentage basis (nutrient-restricted UW ewes were 86% of control-fed UW ewes and nutrient-restricted Baggs ewes were 85% of control-fed Baggs ewes), suggests that the body stores of 2 strains were not affected differently by the nutrient restriction. These data are again consistent with the concept that the ability of nutrient-restricted Baggs ewes to maintain a fetal size similar to their control-fed group is a function of their ability to convert type A placentomes to more efficient forms.
Substrates such as glucose, which is a major energy substrate for the fetus, can directly promote fetal growth and development (Fowden, 1997). In the current study, blood glucose concentrations were significantly reduced in the blood of fetuses from nutrient-restricted UW ewes when compared with fetuses from control-fed UW ewes. In contrast, blood concentrations of glucose were similar for fetuses of control-fed and nutrient-restricted Baggs ewes. The authors have no explanation for the reduced glucose concentration in the blood of fetuses gestated by control-fed Baggs ewes when compared with fetuses gestated by control-fed UW ewes. This may be related to strain differences in fetal metabolic rate and thus glucose utilization, which were not measured in this study but will be the subject of future research. It should be noted, however, that because Baggs fetuses were 30% larger on d 78 than UW fetuses from nutrient-restricted ewes, the total amount of glucose in fetal circulation of Baggs fetuses would actually be higher than that of UW fetuses in the nutrient-restricted group. We have previously reported that essential AA concentrations were also reduced in fetal blood of nutrient-restricted UW vs. control-fed UW pregnancies on d 78 (Kwon et al., 2004), whereas no differences in fetal blood AA concentrations were observed between nutrient-restricted and control-fed Baggs pregnancies (Wu et al., 2005). In contrast, these researchers reported that maternal concentrations of essential AA were reduced on d 78 in nutrient-restricted UW and Baggs ewes compared with their respective control-fed groups. Together, these data are consistent with the concept that the earlier conversion of type A placentomes to more advanced placentomal types in nutrient-restricted Baggs ewes helped to maintain normal concentrations of glucose and AA in fetal blood in the face of a maternal decline. This is supported by the fact that placental efficiency (fetal weight/total placentomal weight) was reduced in nutrient-restricted UW ewes when compared with control-fed UW ewes on d 78 but was similar for control-fed and nutrient-restricted Baggs ewes. Further, Osgerby et al. (2002) reported that a 30% nutrient restriction from d 26 failed to alter placentomal growth trajectory or type by d 90 of gestation, in association with a significant decrease in fetal blood glucose in undernourished vs. control-fed ewes. Again, these data support an association between the ability of a ewe to alter placentomal growth and development during early gestation in response to early gestational nutrient restriction, and increased nutrient delivery to the fetus.
Evidence has linked reduced fetal growth with increased risk of cardiovascular disease in later life (Barker et al., 1990). Whereas growth-retarded fetuses from nutrient-restricted UW ewes in the current study exhibited bilateral ventricular hypertrophy when compared with control-fed UW ewes, the normal size fetuses from nutrient-restricted Baggs ewes did not. We have previously demonstrated upregulation of genes inducing and regulating cellular growth and remodeling in the hypertrophied ventricles of UW ewes subjected to an identical bout of nutrient restriction as utilized in this study (Han et al., 2004; Dong et al., 2005). Further, when the nutrient-restricted UW ewes were realimented to 100% NRC from d 79 to term and allowed to lamb, male offspring developed hypertension by 9 mo of age (Gilbert et al., 2005). These data suggest that the growth restriction experienced by fetuses gestated by nutrient-restricted UW ewes led to altered cardiovascular function in later life, which could affect production efficiency and health.
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IMPLICATIONS
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We have observed different placental responses to a nutritional challenge during pregnancy in ewes of similar breeding but chronically adapted to both different environments and nutrition. The central difference is that ewes adapted to both harsh environments and limited nutrition may initiate the early conversion of type A placentomes to more efficient placentomal types when subjected to an early to mid-gestational nutrient restriction, thereby facilitating nutrient delivery to their developing fetus. These data are consistent with a possible alleviating effect of early placentomal conversion on fetal growth and development in nutrient-restricted Baggs ewes. The exact process that allows Baggs ewes, but not University of Wyoming ewes, to initiate the earlier conversion of placentomes to more advanced types when subjected to early maternal nutrient restriction is unknown at the present time but warrants further investigation.
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Footnotes
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1 The authors thank Carole Hertz for her technical assistance, Robert Stobart for confirming pregnancy status via ultrasonography, and Mark Drumhiller, Britney Burt, and Hyung Chul Han for help with sample collection and processing. Supported, in part, by grants from the University of Wyoming BRIN P20 RR16474 and INBRE P20 RR016474-04, NIH HD 21350, and USDA/NRI 2004-35203-14949. 
2 Current address: Department of Animal and Range Sciences, North Dakota State University, Fargo 58105.
3 Corresponding author: spford{at}uwyo.edu
Received for publication March 6, 2006.
Accepted for publication June 26, 2006.
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Abstract
INTRODUCTION
