First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Uterine spiral artery remodeling (UAR) is essential for placental perfusion and fetal development. A defect in UAR underpins placental ischemia disorders, e.g. preeclampsia, that result in maternal systemic vascular endothelial oxidative stress and dysfunction and hypertension. We have established a model of impaired UAR by prematurely elevating maternal serum estradiol levels during the first trimester of baboon pregnancy. However, it is unknown whether this experimental paradigm is associated with maternal vascular endothelial dysfunction. Therefore, in the present study baboons were administered estradiol on days 25-59 of gestation to suppress UAR and vascular function determined in maternal skeletal muscle obtained on day 165 (term = 184 days). Maternal peripheral serum sFlt-1 levels were 3-fold higher (P <0.05) and skeletal muscle arteriolar endothelial nitric oxide synthase protein expression and luminal area, and skeletal muscle capillary density, were 30-50% lower (P < 0.01) near term in UAR suppressed baboons. Maternal skeletal muscle catalase protein levels, reflecting oxidative stress, were 75% higher (P < 0.05) and mean arterial blood pressure 28% higher (P < 0.01) in UAR defective baboons. We propose that these changes in skeletal muscle, a systemic tissue, were induced by the elevation in sFlt-1, which suppresses vascular endothelial growth factor bioavailability. In summary, maternal skeletal muscle vascular function was disrupted in a baboon model of impaired UAR. These results highlight the translational impact of this primate model and relevance to adverse conditions of human pregnancy underpinned by improper uterine artery transformation.

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Early onset of parturition induced by acute alcohol exposure in C57BL/6J mice: role of uterine PGE and PGF2a

Reproduction Fertility and Development ◽

10.1071/r97083 ◽

1997 ◽

Vol 9 (8) ◽

pp. 815 ◽

Cited By ~ 8

Author(s):

J. L. Cook ◽

C. L. Randall

Keyword(s):

Fetal Growth ◽

Early Onset ◽

Growth And Development ◽

Alcohol Treatment ◽

Alcohol Exposure ◽

Prostaglandin Synthesis ◽

Gestational Length ◽

Synthesis Inhibitor ◽

Prostaglandin Synthesis Inhibitor

These studies were designed to determine the effect of acute alcohol treatment on gestational length and to probe for a mechanism underlying alcohol-induced early onset of parturition (EOP) in mice. Experiment 1: alcohol increases the incidence of EOP. Pregnant C57BL/6J mice were given alcohol (0, 4, 5 or 6 g kg -1 , i.g.) on Gestational Day (GD) 10, 15, 16, 17 or 18. Deliveries were monitored every 6 h from GD 18. Results indicated that 6 g kg -1 alcohol treatment on GD 17 or 18 increased the incidence of EOP. Experiment 2: prostaglandins (PGs) play roles in parturition. The purpose of Experiment 2 was to determine whether PGs mediate alcohol-induced EOP in mice. The results indicated that pretreatment on GD 17 with aspirin, a prostaglandin synthesis inhibitor, prevented alcohol-induced EOP. These data suggest that alcohol-induced EOP in mice may be mediated by PGs. Experiment 3: PGs are influenced by alcohol and are triggers of labour. Experiment3 measured uterine PGs associated with the onset of alcohol-induced EOP in mice. Alcohol increased uterine PGE and PGF2a , with PGE levels higher than control before labour, and elevated PGF2a levels correlating with labour. Changes in gestational length have important implications for pregnancy outcome, as well as for normal fetal growth and development.

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

Animal Production Science ◽

10.1071/an14278 ◽

2014 ◽

Vol 54 (9) ◽

pp. 1333 ◽

Cited By ~ 9

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.

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36: Evaluating the effects of prenatal nicotine exposure and vitamin c supplementation on placental perfusion and development in a non-human primate model

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2014.10.082 ◽

2015 ◽

Vol 212 (1) ◽

pp. S26

Author(s):

Jamie Lo ◽

Matthias Schabel ◽

Victoria Roberts ◽

Terry Morgan ◽

Eliot Spindel ◽

...

Keyword(s):

Vitamin C ◽

Nicotine Exposure ◽

Primate Model ◽

Placental Perfusion ◽

Prenatal Nicotine Exposure ◽

Vitamin C Supplementation ◽

Prenatal Nicotine ◽

Human Primate

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Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking

Translational Psychiatry ◽

10.1038/s41398-021-01728-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daria Piacentino ◽

Silvia Grant-Beurmann ◽

Carlotta Vizioli ◽

Xiaobai Li ◽

Catherine F. Moore ◽

...

Keyword(s):

Amino Acids ◽

Alcohol Use ◽

Alcohol Drinking ◽

Gut Microbiome ◽

Alcohol Exposure ◽

Primate Model ◽

Fecal Microbiome ◽

Excessive Alcohol ◽

Human Primate

AbstractA relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p’s < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p’s < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.

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Placental adaptations in a nonhuman primate model of gestational protein restriction

Journal of Developmental Origins of Health and Disease ◽

10.1017/s204017442000121x ◽

2020 ◽

pp. 1-7

Author(s):

Victoria H.J. Roberts ◽

Jessica E. Gaffney ◽

Terry K. Morgan ◽

Antonio E. Frias

Keyword(s):

Growth Factor ◽

Fetal Growth ◽

Nonhuman Primate ◽

Protein Restriction ◽

Restricted Diet ◽

Nonhuman Primate Model ◽

Primate Model ◽

Placental Perfusion ◽

Taurine Uptake ◽

Protein Restricted Diet

Abstract We previously demonstrated decreased placental perfusion, reduced amniotic fluid protein content, and increased pregnancy loss in a nonhuman primate model of gestational protein restriction. Here, our objective was to link these detrimental findings with a functional placental assessment. As blood flow is critical to maternal-fetal exchange, we hypothesized that a protein-restricted diet would impair placental taurine uptake. Pregnant rhesus macaques were maintained on either control chow (CON, n = 5), a 33% protein-restricted diet (PR33, n = 5), or a 50% PR diet (PR50, n = 5) prior to and throughout pregnancy. Animals were delivered on gestational day 135 (G135; term is G168). Taurine activity was determined in fresh placental villous explants. Taurine transporter (TauT) protein expression, placental growth factor (PLGF), and insulin-like growth factor (IGF)-1 and IGF-2 protein concentrations were measured, and histological assessment was performed. Fetal body weights and placental weights were comparable between all three groups at G135. Placental taurine uptake was decreased in PR33- and PR50-fed animals compared to CON, yet TauT expression was unchanged across groups. PLGF was significantly increased in PR50 vs. CON, with no change in IGF-1 or IGF-2 expression in placental homogenate from PR-fed animals. Accelerated villous maturation was observed in all PR50 cases, three of five PR33, and was absent in CON. We demonstrate conserved fetal growth, despite a decrease in placental taurine uptake. Increased expression of PLGF and expansion of the syncytiotrophoblast surface area in the severely protein-restricted animals suggest a compensatory mechanism by the placenta to maintain fetal growth.

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