scholarly journals Maternal periconceptional and first trimester protein restriction in beef heifers: effects on maternal performance and early fetal growth

2020 ◽  
Vol 32 (9) ◽  
pp. 835
Author(s):  
Katrina J. Copping ◽  
Andrew Hoare ◽  
I. Caroline McMillen ◽  
Raymond J. Rodgers ◽  
Charles R. Wallace ◽  
...  
Keyword(s):  
Fetal Growth ◽  
First Trimester ◽  
Maternal Plasma ◽  
Protein Restriction ◽  
Daily Weight Gain ◽  
Third Trimester ◽  
Plasma Urea ◽  
Low Protein ◽  
Maternal Performance ◽  
Post Period

This study evaluated the effect of protein restriction during the periconception (PERI) and first trimester (POST) periods on maternal performance, physiology and early fetal growth. Yearling nulliparous heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri respectively) beginning 60 days before conception. From 24 to 98 days post-conception (dpc), half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost respectively), yielding four groups in a 2×2 factorial design with a common diet until parturition. Protein restriction was associated with lower bodyweight subsequent to reduced (but positive) average daily weight gain (ADG) during the PERI and POST periods. During the POST period, ADG was greater in LPeri than HPeri heifers and tended to be greater in LPost than HPost heifers during the second and third trimester. Bodyweight was similar at term. The pregnancy rate did not differ, but embryo loss between 23 and 36 dpc tended to be greater in LPeri than HPeri heifers. Overall, a greater proportion of male fetuses was detected (at 60 dpc 63.3% male vs 36.7% female). Protein restriction altered maternal plasma urea, non-esterified fatty acids, progesterone, leptin and insulin-like growth factor 1 at critical stages of fetal development. However, profiles varied depending on the sex of the conceptus.

scholarly journals Maternal bisphenol urine concentrations, fetal growth and adverse birth outcomes: A population-based prospective cohort

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chalana M. Sol ◽  
Charissa van Zwol - Janssens ◽  
Elise M. Philips ◽  
Alexandros G. Asimakopoulos ◽  
Maria-Pilar Martinez-Moral ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Fetal Growth ◽  
Head Circumference ◽  
Lower Risk ◽  
First Trimester ◽  
Population Based ◽  
Third Trimester ◽  
Bisphenol S ◽  
Fetal Head ◽  
Urine Concentrations

Abstract Background Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. Methods In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. Results An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. Conclusions Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

scholarly journals Smoking and Smoking Cessation in the Risk for Fetal Growth Restriction and Low Birth Weight and Additive Effect of Maternal Obesity

2020 ◽  
Vol 9 (11) ◽  
pp. 3504
Author(s):  
Małgorzata Lewandowska ◽  
Barbara Więckowska ◽  
Lidia Sztorc ◽  
Stefan Sajdak
Keyword(s):  
Smoking Cessation ◽  
Birth Weight ◽  
Cigarette Smoking ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Odds Ratio ◽  
Maternal Obesity ◽  
First Trimester ◽  
Third Trimester ◽  
The Mean

Many studies have shown that neonates of smoking mothers have a lower birth weight, but several issues remain poorly studied, e.g., the effects of giving up smoking or the combined effects of smoking and maternal obesity. Therefore, we evaluated a prospective cohort of 912 mothers in a single pregnancy, recruited in Poland, in 2015−2016. In the cohort, we recorded 72 (7.9%) newborns with birth weight <10th percentile, 21 (2.3%) fetal growth restriction (FGR) cases, and 60 (6.6%) low birth weight (LBW, <2500 g) newborns. In the cohort, 168 (18.4%) women smoked before pregnancy; the mean number of cigarettes/day was 10.8 (1–30), and the mean number of years of cigarette smoking was 8.5 (1–25). Among smokers, 57 (6.3%) women smoked in the first trimester. Adjusted odds ratio (AOR) of newborn outcomes (with 95% confidence intervals, CI) was calculated in multi-dimensional logistic regressions. Compared to participants who had never smoked, smoking before pregnancy was associated with a higher odds ratio of birth weight <10th percentile (AOR = 1.93, CI: 1.08–3.44, p = 0.027), but the result for LBW (AOR = 2.76, CI: 1.05–7.26, p = 0.039) and FGR (AOR = 1.13, CI: 0.38–3.36, p = 0.822) had the wider confidence interval or was insignificant. Effects of smoking cessation before pregnancy were statistically insignificant for the studied outcomes. Smoking in the first trimester was associated with a higher risk of birth weight <10th percentile (AOR = 4.68, CI: 2.28–9.62, p < 0.001), LBW (AOR = 6.42, CI: 1.84–22.36, p = 0.004), and FGR (AOR = 3.60, CI: 0.96–13.49, p = 0.057). Smoking cessation in the second/third trimester was associated with a higher odds ratio of birth weight <10th percentile (AOR = 4.54, CI: 1.58–13.02, p = 0.005), FGR (AOR = 3.36, CI: 0.6–18.74, p = 0.167), and LBW (AOR = 2.14, CI: 0.62–7.36), p = 0.229), to a similar degree to smoking in the first trimester. The odds ratios were higher in the subgroup of pre-pregnancy body mass index ≥25 kg/m2 for the risk of birth weight <10th percentile (AOR = 6.39, CI: 2.01–20.34, p = 0.002) and FGR (AOR = 6.25, CI: 0.86–45.59, p = 0.071). The length of cigarette smoking time was also the risk factor for studied outcomes. Conclusions: Smoking in the first trimester increased the studied risks, and the coexistence of excessive maternal weight increased the effects. Smoking cessation during the second/third trimester did not have a protective effect.

scholarly journals Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

2000 ◽  
pp. 683-687 ◽  
Author(s):  
K Kobayashi ◽  
T Kubota ◽  
T Aso ◽  
Y Hirata ◽  
T Imai ◽  
...  
Keyword(s):  
Northern Blot Analysis ◽  
Plasma Concentrations ◽  
Placental Tissue ◽  
First Trimester ◽  
Maternal Plasma ◽  
Placental Lactogen ◽  
Third Trimester ◽  
Maternal Circulation ◽  
The Third ◽  
System A

Adrenomedullin (AM) is a novel vasorelaxant peptide, isolated from human pheochromocytoma. Although AM may be involved in the regulation of the cardiovascular system, a number of other mechanisms are also involved. The present study was undertaken to confirm the presence of AM in human maternal circulation and in placental function during pregnancy. Immunoreactive (ir) AM concentrations in maternal plasma were 3.4+/-0.7fmol/ml (mean+/-s.e. m.) in the first trimester, 3.3+/-1.1fmol/ml in the second trimester, 7.3+/-2.8fmol/ml in the third trimester, 4.1+/-1.9fmol/ml in early puerperium and 3.0+/-0.4fmol/ml in non-pregnant periods; the concentration in the third trimester was significantly greater than those in other periods. Plasma concentrations of estradiol (E(2)), progesterone, human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were also measured, using RIA kits. Significant correlations have been demonstrated between the concentrations of irAM and those of E(2), progesterone and hPL. We therefore examined the expression of AM within the placental tissues using immunohistochemistry and northern blot analysis in order to demonstrate a correlation between the presence of AM in the placenta and maternal plasma. Using immunohistochemistry, we detected AM in the amnion at term and the expression of AM mRNA in human placental tissues using cloned human (h) AM complementary DNA as a probe. This study demonstrates the immunoreactivity of human hAM in maternal plasma during pregnancy, and suggests that hAM in maternal plasma is generated partly from placental tissue.

scholarly journals Maternal periconceptional and first trimester protein restriction in beef heifers: effects on placental parameters and fetal and neonatal calf development

2020 ◽  
Vol 32 (5) ◽  
pp. 495 ◽  
Author(s):  
K. J. Copping ◽  
J. Hernandez-Medrano ◽  
A. Hoare ◽  
K. Hummitzsch ◽  
I. C. McMillen ◽  
...  
Keyword(s):  
Gene Expression ◽  
First Trimester ◽  
Protein Restriction ◽  
Hepatic Gene Expression ◽  
Placental Development ◽  
Early Gestation ◽  
Neonatal Calf ◽  
Low Protein ◽  
Functional Consequences ◽  
Glucose Output

Few studies have investigated the effects of nutrition during the periconception and early gestation periods on fetal and placental development in cattle. In this study, nulliparous yearling heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri) beginning 60 days before conception. From 24 to 98 days after conception, half of each treatment group was changed to the alternative high- or low-protein diet (HPost and LPost) yielding four groups in a 2×2 factorial design. A subset of heifers (n=46) was necropsied at 98 days after conception and fetoplacental development assessed. Placentome number and volume decreased in response to LPeri and LPost diets respectively. Absolute lung, pancreas, septum and ventricle weights decreased in LPost versus HPost fetuses, whereas the post-conception diet altered absolute and relative liver and brain weights depending on sex. Similarly, changes in fetal hepatic gene expression of factors regulating growth, glucose output and lipid metabolism were induced by protein restriction in a sex-specific manner. At term, neonatal calf and placental measures were not different. Protein restriction of heifers during the periconception and early gestation periods alters fetoplacental development and hepatic gene expression. These changes may contribute to functional consequences for progeny, but this may not be apparent from gross morphometry at birth.

scholarly journals The maternal endocrine environment in the low-protein model of intra-uterine growth restriction

2003 ◽  
Vol 90 (4) ◽  
pp. 815-822 ◽  
Author(s):  
D. S. Fernandez-Twinn ◽  
S. E. Ozanne ◽  
S. Ekizoglou ◽  
C. Doherty ◽  
L. James ◽  
...  
Keyword(s):  
Maternal Plasma ◽  
Protein Restriction ◽  
Control Group ◽  
Adult Disease ◽  
Fetal Plasma ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Uterine Growth ◽  
Placental Blood ◽  
Mechanistic Basis

Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto–placental blood were raised significantly (P=0·04 and P=0·0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0·04), prolactin levels were raised (P=0·047) and progesterone levels were reduced (P=0·02). Circulating 17β-oestradiol in the LP dams was raised by 35% over those of the controls from day 17 to day 21 (P=0·008). A significant decrease in maternal leptin levels (P=0·004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.

scholarly journals Nutrition During Pregnancy: Findings from the NICHD Fetal Growth Studies – Singleton Cohort

2020 ◽  
Author(s):  
Stefanie N Hinkle ◽  
Cuilin Zhang ◽  
Katherine L Grantz ◽  
Anthony Sciscione ◽  
Deborah A Wing ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Fetal Growth ◽  
First Trimester ◽  
Healthy Eating Index ◽  
Dietary Guidelines ◽  
Dietary Quality ◽  
Dietary Intakes ◽  
Third Trimester ◽  
Growth Studies ◽  
Race Ethnicity

Abstract Background Accumulating evidence indicates that maternal diets are important for optimizing maternal and offspring health. Existing research lacks comprehensive profiles of maternal diets throughout pregnancy, especially in a racially/ethnically diverse obstetrical population. Objective To characterize diets in a longitudinal U.S. pregnancy cohort by trimester, race/ethnicity, and pre-pregnancy body mass index (BMI). Methods Data were obtained from pregnant women in the NICHD Fetal Growth Studies - Singleton cohort (2009–2013). A Food Frequency Questionnaire (FFQ) at 8–13 weeks gestation assessed periconception and first trimester diet (n = 1615). Automated, self-administered, 24-hour dietary recalls targeted at 16–22, 24–29, 30–33, and 34–37 weeks gestation assessed second and third trimester diets (n = 1817 women/6791 recalls). Healthy Eating Index-2010 (HEI) assessed diet quality (i.e., adherence to U.S. Dietary Guidelines). Variations in weighted energy-adjusted means for foods and nutrients were examined by trimester, self-identified race/ethnicity, and self-reported pre-pregnancy BMI. Results Mean (95% confidence interval) HEI was 65.9 (64.9,67.0) during periconception to first trimester assessed with an FFQ, and 51.6 (50.8,52.4) and 51.5 (50.7,52.3) during the second trimester and third trimester, respectively, assessed using 24-hour recalls. No significant differences were observed between second and third trimester in macronutrients, micronutrients, foods, or HEI components (P ≥ 0.05). Periconception to first trimester HEI was highest among Asian/Pacific Islander [67.2 (65.9,68.6)] and lowest among non-Hispanic Black [58.7 (57.5,60.0)] women and highest among women with normal weight [67.2 (66.1,68.4)] and lowest among women with obesity [63.5 (62.1,64.9)]. Similar rankings were observed in the second/third trimesters. Conclusions Most pregnant women in this cohort reported dietary intakes that, on average, did not meet U.S. Dietary Guidelines for non-pregnant individuals. Also, diet differed across race/ethnic groups and by pre-pregnancy BMI with lowest overall dietary quality in all trimesters among non-Hispanic Black women and women with obesity. No meaningful changes in dietary intake were observed between the second and third trimesters.

scholarly journals MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE

2016 ◽  
Vol 49 (3) ◽  
pp. 392-407 ◽  
Author(s):  
Eva Pölzlberger ◽  
Beda Hartmann ◽  
Erich Hafner ◽  
Ingrid Stümpflein ◽  
Sylvia Kirchengast
Keyword(s):  
Fetal Growth ◽  
Weight Status ◽  
First Trimester ◽  
Growth Patterns ◽  
Maternal Height ◽  
Third Trimester ◽  
Crown Rump Length ◽  
Gestational Weight ◽  
Pregnancy Weight ◽  
Newborn Size

SummaryThe impact of maternal height, pre-pregnancy weight status and gestational weight gain on fetal growth patterns and newborn size was analysed using a dataset of 4261 singleton term births taking place at the Viennese Danube Hospital between 2005 and 2013. Fetal growth patterns were reconstructed from three ultrasound examinations carried out at the 11th/12th, 20th/21th and 32th/33th weeks of gestation. Crown–rump length, biparietal diameter, fronto-occipital diameter, head circumference, abdominal transverse diameter, abdominal anterior–posterior diameter, abdominal circumference and femur length were determined. Birth weight, birth length and head circumference were measured immediately after birth. The vast majority of newborns were of normal weight, i.e. between 2500 and 4000 g. Maternal height showed a just-significant but weak positive association (r=0.03: p=0.039) with crown–rump length at the first trimester and with the majority of fetal parameters at the second trimester (r>0.06; p<0.001) and third trimester (r>0.09; p<0.001). Pre-pregnancy weight status was significantly positively associated with nearly all fetal dimensions at the third trimester (r>0.08; p<0.001). Maternal height (r>0.17; p<0.001) and pre-pregnancy weight status (r>0.13; p<0.001), but also gestational weight gain (r>0.13; p<0.001), were significantly positively associated with newborn size. Some of these associations were quite weak and the statistical significance was mainly due to the large sample size. The association patterns between maternal height and pre-pregnancy weight status with fetal growth patterns (p<0.001), as well as newborn size (p<0.001), were independent of maternal age, nicotine consumption and fetal sex. In general, taller and heavier women gave birth to larger infants. This association between maternal size and fetal growth patterns was detectable from the first trimester onwards.

scholarly journals Fetal programming in 2-year-old calving heifers: peri-conception and first trimester protein restriction alters fetal growth in a gender-specific manner

2014 ◽  
Vol 54 (9) ◽  
pp. 1333 ◽  
Author(s):  
K. J. Copping ◽  
A. Hoare ◽  
M. Callaghan ◽  
I. C. McMillen ◽  
R. J. Rodgers ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Programming ◽  
Growth And Development ◽  
Dietary Intervention ◽  
Maternal Nutrition ◽  
First Trimester ◽  
Protein Restriction ◽  
Production Traits ◽  
Long Term Effects ◽  
Crown Rump Length

Protein restriction in early bovine gestation affects post-natal reproduction and production traits in progeny. This experiment evaluated the effects of dietary protein restriction during the peri-conception period and first trimester in yearling heifers on conceptus growth and development; this period of dietary intervention being earlier than any previous bovine fetal programming studies. Three-hundred and sixty primiparous 12-month-old Santa Gertrudis heifers were individually fed high [14% crude protein (CP)] or low (7% CP) diets for 60 days before conception. At 23 days post-conception (dpc), each high (HPERI) or low (LPERI) group was again split into high (HPOST) or low (LPOST) protein groups yielding four treatment groups in a 2 × 2 factorial design. From the end of the first trimester of gestation (98dpc), the pregnant heifers were individually fed a 12% CP diet until parturition. Forty-six fetuses were excised at 98dpc. Sixty-four heifers went on to calve. Conceptus development was assessed via transrectal ultrasound from 36dpc, fetal necropsy at 98dpc and live calf measures at term. At 36dpc, HPERI diet increased fetal crown–rump length (CRL) (P < 0.05) and at the 60dpc scan, biparietal diameter (BPD) tended to be increased by HPOST diet (P < 0.1) though the greater effect upon BPD was still the HPERI diet (P < 0.05). At 60dpc, BPD in the male fetus was affected by the peri-conception diet (P < 0.05), while in females, BPD was not different among nutritional groups. These ultrasound measures of fetal growth were validated by measures of the excised fetus at 98dpc. Fetal weight was heavier (P < 0.01) in those whose mothers were fed the HPOST diet than their LPOST counterparts. Males fetuses were heavier than female fetuses (P < 0.001). Fetal CRL was increased by HPERI diet (P < 0.05) and tended to be increased by HPOST diet (P < 0.1). Fetal BPD tended to be increased by HPERI diet (P < 0.1). In males, BPD tended to be increased in those fetuses whose mothers were fed HPERI (P < 0.1). For females, maternal nutrition during PERI or POST did not affect BPD at 98dpc (P > 0.1). At term, no dietary effect on birthweight was observed (P > 0.1) and males were not heavier than females (P > 0.1). These results suggest that maternal protein intake during the peri-conception (–60 to 23dpc) and first trimester (24–98dpc) may influence early conceptus growth and development in the bovine. The long-term effects on offspring metabolism and post-natal development of this dietary intervention are yet to be determined.

scholarly journals Serum levels of pro- and anti-inflammatory cytokines in non-pregnant women, during pregnancy, labour and abortion

1998 ◽  
Vol 7 (2) ◽  
pp. 69-72 ◽  
Author(s):  
S. Vassiliadis ◽  
A. Ranella ◽  
L. Papadimitriou ◽  
A. Makrygiannakis ◽  
I. Athanassakis
Keyword(s):  
Fetal Growth ◽  
Serum Levels ◽  
First Trimester ◽  
Therapeutic Interventions ◽  
Third Trimester ◽  
Time Intervals ◽  
Gm Csf ◽  
Naturally Occurring ◽  
Tnf Α ◽  
Microbial Infections

Disturbance of the cytokine equilibrium has been accused for many pathological disorders. Microbial infections, autoimmune diseases, graft rejection have been correlated to over- or under-production of specific cytokines which are produced as responder molecules to the various immune stimuli. The sole naturally occurring immune reaction in the organism is developed during the gestational period where, despite the presence of a semi-allogeneic graft, maternal immunoreactivity is driven to support fetal growth. The successful embryo development has been attributed to the important intervention of cytokines where some have been characterized as indispensable and others deleterious to fetal growth. However, the physiological levels of many factors during the gestational process have not been determined. Thus, in the present study we have measured and established the values of IL-1α, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, GM-CSF, TNF- α and IFN-γ during all phases of human pregnancy (first, second and third trimester of pregnancy, labour, abortions of the first trimester) as well as in the non-pregnant control state. This is an attempt to assess serum protein concentrations and present the physiological levels of these cytokines at certain time intervals providing thus a diagnostic advantage in pregnancy cases where the mother cannot immunologically support the fetus. Exploitation of this knowledge and further research may be useful for therapeutic interventions in the future.

scholarly journals Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1119-1129 ◽  
Author(s):  
Fredrick J. Rosario ◽  
Nina Jansson ◽  
Yoshikatsu Kanai ◽  
Puttur D. Prasad ◽  
Theresa L. Powell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fetal Growth ◽  
Mammalian Target Of Rapamycin ◽  
Protein Restriction ◽  
Amino Acid Transporters ◽  
Signal Transducer ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Igf I ◽  
Transcription 3

The mechanisms underlying reduced fetal growth in response to maternal protein restriction are not well established. Maternal levels of insulin, IGF-I, and leptin are decreased in rats fed a low protein (LP) diet. Because these hormones stimulate placental amino acid transporters in vitro, we hypothesized that maternal protein restriction inhibits placental leptin, insulin/IGF-I, and mammalian target of rapamycin signaling and down-regulates the expression and activity of placental amino acid transporters. Pregnant rats were fed either an isocaloric low protein (LP, 4% protein) or control diet (18% protein) and studied at gestational day (GD)15, GD19, or GD21 (term 23). At GD19 and GD21, placental expression of phosphorylated eukaryotic initiation factor 4E binding protein 1 (Thr-36/46 or Thr-70) and phosphorylated S6 ribosomal protein (Ser-235/236) was decreased in the LP group. In addition, placental expression of phosphorylated S6 kinase 1 (Thr-389), phosphorylated Akt (Thr-308), and phosphorylated signal transducer and activator of transcription 3 (Tyr-705) was reduced at GD21. In microvillous plasma membranes (MVM) isolated from placentas of LP animals, protein expression of the sodium-coupled neutral amino acid transporter (SNAT)2 and the large neutral amino acid transporters 1 and 2 was reduced at GD19 and GD21. MVM SNAT1 protein expression was reduced at GD21 in LP rats. SNAT4 and 4F2 heavy chain expression in MVM was unaltered. System A and L amino acid transporter activity was decreased in MVM from LP animals at GD19 and GD21. In conclusion, maternal protein restriction inhibits placental insulin, mammalian target of rapamycin signaling, and signal transducer and activator of transcription 3 signaling, which is associated with a down-regulation of placental amino acid transporters. We speculate that maternal endocrine and metabolic control of placental nutrient transport reduces fetal growth in response to protein restriction.

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