Maternal Liver Research Articles

Exposure to ambient air pollution and indicators of maternal liver function during pregnancy: Findings from a birth cohort study in Foshan City, Southern China

Evidence concerning the associations between gestational air pollution exposure and maternal liver function is scarce. We explored this topic by analyzing data from a birth cohort study conducted in Foshan city, Southern China. Between 2015 and 2019, we recruited a total of 49,568 pregnant women from 16 hospitals in Foshan city. Basic socio-demographical information and lifestyle factors was collected from the hospital medical records. Daily PM2.5, PM10, SO2, NO2, and O3 exposure of each participant during study period was assessed by inverse-distance weighted method. Then, we assigned the average air pollutant levels during trimester 1, trimester 2, and the first two trimesters to each participant. Liver function indicators (liver enzymes, serum protein, and serum bilirubin) of each participant were measured during their third trimester prenatal visit. Mixed-effects linear and logistic regression models were used to evaluate the associations of gestational air pollution exposure and maternal liver function indicators. Our findings suggested that maternal exposure to air pollution during pregnancy, especially trimester 2, was associated with increased liver enzyme levels and decreased serum protein levels.

Effects of Maternal Gut Microbiota-Targeted Therapy on the Programming of Nonalcoholic Fatty Liver Disease in Dams and Fetuses, Related to a Prenatal High-Fat Diet.

Metabolic disorders can start in utero. Maternal transmission of metabolic phenotypes may increase the risks of adverse metabolic outcomes, such as nonalcoholic fatty liver disease (NAFLD); effective intervention is essential to prevent this. The gut microbiome plays a crucial role in fat storage, energy metabolism, and NAFLD. We investigated the therapeutic use of probiotic Lactobacillus reuteri and postbiotic butyrate gestation in the prevention of perinatal high-fat diet-induced programmed hepatic steatosis in the offspring of pregnant Sprague–Dawley rats who received regular chow or a high-fat (HF) diet 8 weeks before mating. L. reuteri or sodium butyrate was administered via oral gavage to the gestated rats until their sacrifice on day 21 of gestation. Both treatments improved liver steatosis in pregnant dams; L. reuteri had a superior effect. L. reuteri ameliorated obesity and altered the metabolic profiles of obese gravid dams. Maternal L. reuteri therapy prevented maternal HF diet-induced fetal liver steatosis, and reformed placental remodeling and oxidative injury. Probiotic therapy can restore lipid dysmetabolism in the fetal liver, modulate nutrient-sensing molecules in the placenta, and mediate the short-chain fatty acid signaling cascade. The therapeutic effects of maternal L. reuteri on maternal NAFLD and NAFLD reprogramming in offspring should be validated for further clinical translation.

Resveratrol Supplementation in Obese Pregnant Rats Improves Maternal Metabolism and Prevents Increased Placental Oxidative Stress.

Maternal obesity (MO) causes maternal and fetal oxidative stress (OS) and metabolic dysfunction. We investigated whether supplementing obese mothers with resveratrol improves maternal metabolic alterations and reduces OS in the placenta and maternal and fetal liver. From weaning through pregnancy female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating until 19 days’ gestation (dG), half the rats received 20 mg resveratrol/kg/d orally (Cres and MOres). At 19dG, maternal body weight, retroperitoneal fat adipocyte size, metabolic parameters, and OS biomarkers in the placenta and liver were determined. MO mothers showed higher body weight, triglycerides and leptin serum concentrations, insulin resistance (IR), decreased small and increased large adipocytes, liver fat accumulation, and hepatic upregulation of genes related to IR and inflammatory processes. Placenta, maternal and fetal liver OS biomarkers were augmented in MO. MOres mothers showed more small and fewer large adipocytes, lower triglycerides serum concentrations, IR and liver fat accumulation, downregulation of genes related to IR and inflammatory processes, and lowered OS in mothers, placentas, and female fetal liver. Maternal resveratrol supplementation in obese rats improves maternal metabolism and reduces placental and liver OS of mothers and fetuses in a sex-dependent manner.

Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System

Simple SummaryEthanol is the most consumed drug worldwide, even during pregnancy. One of its adverse outcomes is fetal growth restriction, an alteration in development due to decreased IGF-1 levels. Several studies have shown that ethanol can impair the IGF-1 signaling pathway, thus exacerbating IGF-1 adverse effects in both intrauterine and postnatal growth and development. In this manuscript, we used a partially IGF-1-deficient mouse model to demonstrate the key role of IGF-1 in fetal development, as well as ethanol’s adverse effects on CYP2E1 expression levels and the antioxidant enzyme system during pregnancy.Ethanol use during pregnancy is a risk factor for developing adverse outcomes. Its metabolism by cytochrome P450 2E1 (CYP2E1) produces radical oxygen species (ROS), promoting cellular injury and apoptosis. To date, no studies have been conducted to elucidate the teratogenic effects due to both IGF-1 deficiency and ethanol consumption in mice placentas. The aim of this study is to determine the effect of ethanol consumption on the placenta and liver of partially IGF-1-deficient mice, the role of metabolism via CYP2E1, and the antioxidant enzyme system. Heterozygous (HZ, Igf1+/−) pregnant female mice were given water or 10% ethanol. Wild-type (WT, Igf1+/+) female mice were used as controls. At gestational day 19, pregnant dams were euthanized, and maternal liver and placentas were collected. Pregnant HZ dams were smaller than controls, and this effect was higher due to ethanol consumption. Cyp2e1 gene was overexpressed in the liver of HZ pregnant dams exposed to ethanol; at the protein level, CYP2E1 is reduced in placentas from all genotypes. The antioxidant enzymatic system was altered by ethanol consumption in both the maternal liver and placenta. The results in this work hint that IGF-1 is involved in intrauterine development because its deficiency exacerbates ethanol’s effects on both metabolism and the placenta.

Association of COVID-19 vaccination before conception with maternal liver function during early pregnancy: a cohort study of 7745 Chinese pregnant women

ABSTRACT Multicenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 μmol/L (β = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.

The Correlation and Copathogenesis of Coronary Aortic Sandwich and Renal Cysts.

Objective To determine the correlation for aortic occlusion and hydronephrosis and the pathogenesis of copathogenesis. Methods A retrospective census was established to probe the correlation with renal cysts by gathering aortic coarctation details concerning generic symptoms, diabetes, and liver and kidney profiles from 244 hospitalized aortic clinographers from April 2014 to December 2021 (study category, SG category), 150 hypertensive clients with primary hypertension attending our institution in the same period (matched category, MG category), and 150 able-bodied volunteers (control category, CG category). Results (1) Intercategory discrepancies in regard to aortic occlusion, diabetic malfunction, and kidney and liver abnormality were neither mutually nor predominantly measured (P > 0.05); (2) 244 enrolled SG for aortic occlusion and 150 CG for aortic occlusion were categorized by whether or not aortic occlusion was manifested, and the correlation between maternal age, gender, diabetic malfunction, and kidney and liver abnormality and renal cysts was estimated. The correlation of clogged aorta was demonstrated by a multifactorial logistic regression with gender and the presence of renal cysts (P < 0.05); (3) the correlation of clogged aorta was demonstrated by a multifactorial logistic regression with renal cysts as an independent risk factor for clogged aorta (95% CI: 1.028–10.291;P = 0.031). Conclusion As renal cysts are an autonomous risk of aortic coarctation, it is recommendable to strengthen clinical investigations such as monitoring of clinical blood pressures in kidney cyst recipients to assess their aortic function in order to evaluate their prognosis and minimize the prevalence of aortic coarctation.

Vitamin and Mineral Supplementation and Rate of Gain in Beef Heifers II: Effects on Concentration of Trace Minerals in Maternal Liver and Fetal Liver, Muscle, Allantoic, and Amniotic Fluids at Day 83 of Gestation.

Simple SummaryTrace minerals play a critical role in several biological functions, being essential for fetal growth and development. Maternal nutrition influences the supply of trace minerals to the fetus, which can lead to long-term consequences on offspring performance and health. Our study shows that a maternal vitamin and mineral supplementation (VTM) pre-breeding and during the first trimester of gestation resulted in greater concentrations of Se, Cu, and Co in the liver of beef heifers and their fetuses. These minerals are an essential component of the antioxidant system, which may have positive impacts on the immune system of the future offspring. In addition, we reported that low rates of gain (LG, 0.28 kg/d) from breeding to d 83 of gestation resulted in greater concentrations of Mo and Co in fetal liver compared with moderate rates of gain (MG, 0.79 kg/d). Having a greater fetal trace mineral reserve may be beneficial for neonates, as the immune system of newborn calves is underdeveloped and minerals play a role in that development. Therefore, our study shows that liver weight and concentrations of hepatic trace minerals are affected by maternal dietary treatments, which may impact the performance and health of the future offspring.We evaluated the effects of vitamin and mineral supplementation (from pre-breeding to day 83 of gestation) and two rates of gain (from breeding to day 83 of gestation) on trace mineral concentrations in maternal and fetal liver, fetal muscle, and allantoic (ALF) and amniotic (AMF) fluids. Crossbred Angus heifers (n = 35; BW = 359.5 ± 7.1 kg) were randomly assigned to one of two vitamin and mineral supplementation treatments (VMSUP; supplemented (VTM) vs. unsupplemented (NoVTM)). The VMSUP factor was initiated 71 to 148 d before artificial insemination (AI), allowing time for the mineral status of heifers to be altered in advance of breeding. The VTM supplement (113 g·heifer−1·d−1) provided macro and trace minerals and vitamins A, D, and E to meet 110% of the requirements specified by the NASEM, and the NoVTM supplement was a pelleted product fed at a 0.45 kg·heifer−1·day−1 with no added vitamin and mineral supplement. At AI, heifers were assigned to one of two rates of gain treatments (GAIN; low gain (LG) 0.28 kg/d or moderate gain (MG) 0.79 kg/d) within their respective VMSUP groups. On d 83 of gestation fetal liver, fetal muscle, ALF, and AMF were collected. Liver biopsies were performed prior to VMSUP factor initiation, at the time of AI, and at the time of ovariohysterectomy. Samples were analyzed for concentrations of Se, Cu, Zn, Mo, Mn, and Co. A VMSUP × GAIN × day interaction was present for Se and Cu (p < 0.01 and p = 0.02, respectively), with concentrations for heifers receiving VTM being greater at AI and tissue collection compared with heifers not receiving VTM (p < 0.01). A VMSUP × day interaction (p = 0.01) was present for Co, with greater (p < 0.01) concentrations for VTM than NoVTM at the time of breeding. VTM-MG heifers had greater concentrations of Mn than all other treatments (VMSUP × GAIN, p < 0.01). Mo was greater (p = 0.04) for MG than LG, while Zn concentrations decreased throughout the experiment (p < 0.01). Concentrations of Se (p < 0.01), Cu (p = 0.01), Mn (p = 0.04), and Co (p = 0.01) were greater in fetal liver from VTM than NoVTM. Mo (p ≤ 0.04) and Co (p < 0.01) were affected by GAIN, with greater concentrations in fetal liver from LG than MG. In fetal muscle, Se (p = 0.02) and Zn (p < 0.01) were greater for VTM than NoVTM. Additionally, Zn in fetal muscle was affected by GAIN (p < 0.01), with greater concentrations in LG than MG. The ALF in VTM heifers (p < 0.01) had greater Se and Co than NoVTM. In AMF, trace mineral concentrations were not affected (p ≥ 0.13) by VMSUP, GAIN, or their interaction. Collectively, these data suggest that maternal nutrition pre-breeding and in the first trimester of gestation affects fetal reserves of some trace minerals, which may have long-lasting impacts on offspring performance and health.

Liver embryogenesis and physiological markers associated with induced cholestasis in fetus and pregnant rats

Current study was designed to investigate the effect of induced cholestasis in female rats on fetal growth and maternal livers during different gestational periods (12.5, 14.5, 16.5, 18.5, 20.5) days and to evaluate the role of the amino acid arginine as a preventive and metabolic factor against complications of cholestasis in pregnant females. Observations of macroscopic changes in the groups of pregnant females affected by cholestasis and the treated with arginine compared with females of control group. Changes recorded in each of the uterine horns, mothers' livers, fetuses and placenta uterus, some uterine atrophy, reduction and atrophy in one of the two uterine horns, fibrosis and atrophy were also observed in some of two uterine horns in fetuses, while there was a homogeneous distribution of fetuses between the two uterine horns in the females of the control group and during different pregnancies periods.

Selective modulation of placental and fetal MDR transporters by chronic in utero exposure to NRTIs in Sprague-Dawley rats: Importance for fetoprotection

Multidrug resistance (MDR) transporters present in placenta and fetal tissues reduce intracellular accumulation of their substrates. Consequently, induction of protein expression may further reduce toxic effects of specific xenobiotics. This work aimed to study whether sustained drug treatments in utero could modulate MDR transporters P-gp, BCRP, and MRP2 and thus impact their fetoprotective action. Pregnant Sprague-Dawley rats were daily treated by gavage with zidovudine (AZT, 60 mg/kg) or lamivudine (3TC, 30 mg/kg) from gestation day (GD) 11 to 20. On GD 21, DNA damage and MDR protein abundance were assessed by comet assay and western blotting, respectively. Moreover, a single IV dose of AZT or 3TC was administered on GD 21 and drug concentrations were measured in maternal blood and fetal liver by HPLC-UV. Chronic exposure to 3TC caused significantly higher DNA damage than AZT in fetal liver cells, whereas no differences were observed in maternal blood cells. Increased levels of BCRP protein were found in the placenta and fetal liver after AZT, but not 3TC, chronic in utero exposure. Contrarily, no modifications in the protein abundance of P-gp or MRP2 were found after sustained exposure to these drugs. The area under the curve of AZT in fetal liver was significantly lower in the AZT-pretreated rats than in the VEH or 3TC groups. Moreover, pre-administration of the BCRP inhibitor gefitinib (20 mg/kg, IP) increased AZT levels to the values observed in the VEH-treated group in this tissue. On the other hand, the disposition of 3TC in maternal blood or fetal liver was not modified after chronic treatment in either group. In conclusion, chronic exposure to AZT selectively induces BCRP expression in the placenta and fetal liver decreasing its own accumulation which may account for the lower DNA damage observed for AZT compared to 3TC in fetal liver cells.

Di-2-ethylhexyl phthalate affects zinc metabolism and neurogenesis in the developing rat brain

We previously observed that developmental marginal zinc deficiency affects neurogenesis. Maternal phthalate exposure could disrupt fetal zinc homeostasis by triggering an acute phase response, causing maternal liver zinc retention that limits zinc availability to the fetus. Thus, we currently investigated whether exposure to di-2-ethylhexyl phthalate (DEHP) during gestation in rats alters fetal brain neurogenesis by impairing zinc homeostasis. Dams consumed an adequate (25 μg zinc/g diet) (C) or a marginal zinc deficient (MZD) (10 μg zinc/g diet) diet, without or with DEHP (300 mg/kg BW) (C + DEHP, MZD + DEHP) from embryonic day (E) 0 to E19. To evaluate neurogenesis we measured parameters of neural progenitor cells (NPC) proliferation and differentiation. Maternal exposure to DEHP and/or zinc deficiency lowered fetal brain cortical tissue (CT) zinc concentrations. Transcription factors involved in NPC proliferation (PAX6, SOX2, EMX1), differentiation (TBR2, TBR1) and mature neurons (NeuN) were lower in MZD, MZD + DEHP and C + DEHP than in C E19 brain CT, being the lowest in the MZD + DEHP group. VGLUT1 levels, a marker of glutamatergic neurons, showed a similar pattern. Levels of a marker of GABAergic neurons, GAD65, did not vary among groups. Phosphorylated ERK1/2 levels were reduced by both MZD and DEHP, and particularly in the MZD + DEHP group. MEHP-treated human neuroblastoma IMR-32 cells and E19 brains from DEHP-treated dams showed that the zinc-regulated phosphatase PP2A can be in part responsible for DEHP-mediated ERK1/2 downregulation and impaired neurogenesis. Overall, gestational exposure to DEHP caused secondary zinc deficiency and impaired neurogenesis. These harmful effects could have long-term consequences on the adult offspring brain structure and function.

Butyrate ameliorates maternal high-fat diet-induced fetal liver cellular apoptosis.

A maternal high-fat diet (HFD) can impact the offspring’s development of liver steatosis, with fetal development in utero being a crucial period. Therefore, this study investigated the mechanism and whether butyrate can rescue liver injury caused by maternal HFD in the fetus. Pregnant female Sprague Dawley rats were randomly divided into two groups, prenatal HFD (58% fat) exposure or normal control diet (4.5% fat). The HFD group was fed an HFD 7 weeks before mating and during gestation until sacrifice at gestation 21 days. After confirmation of mating, the other HFD group was supplemented with sodium butyrate (HFSB). The results showed that maternal liver histology showed lipid accumulation with steatosis and shortened ileum villi in HFD, which was ameliorated in the HFSB group (P<0.05). There was increased fetal liver and ileum TUNEL staining and IL-6 expression with increased fetal liver TNF-α and malondialdehyde expression in the HFD group (P<0.05), which decreased in the HFSB group (P<0.05). The fetal liver expression of phospho-AKT/AKT and GPX1 decreased in the HFD group but increased in the HFSB group (P<0.05). In conclusion that oxidative stress with inflammation and apoptosis plays a vital role after maternal HFD in the fetus liver that can be ameliorated with butyrate supplementation.

Maternal transfer of pharmaceuticals and personal care products in the Brazilian guitarfish Pseudobatos horkelii

Maternal transfer is a notable contaminant source for elasmobranchs during the embryonic development. The maternal offloading of several compounds has been evaluated, especially concerning legacy contaminants. However, information on pharmaceuticals and personal care products (PPCPs) offload and, consequently, embryonic exposure in elasmobranchs is still unknown. Despite this, previous detection of PPCPs in pregnant females suggested the maternal offloading of these compounds in the Brazilian guitarfish Pseudobatos horkelii, yet progeny levels were not investigated. For this reason, our goal was to estimate and describe the maternal transfer of four PPCPs in P. horkelii. Diclofenac, methylparaben, octocrylene and triclosan were determined in liver and uterine content samples of five pregnant females using gas chromatography coupled to mass spectrometry. Diclofenac and methylparaben were detected in maternal and uterine content samples, whereas octocrylene and triclosan were only detected in maternal livers. This suggests that diclofenac and methylparaben are transferred to the offspring, at maximum transfer capacities of 27% and 6%, respectively. The lack of detection of other analytes in uterine content suggests that these contaminants might not be transferred. The concentrations observed for diclofenac and methylparaben are similar to those reported in adult elasmobranchs and teleosts, showing that embryos are exposed to considerable levels during their development. In addition, maternal diclofenac concentrations were not influenced by maternal size, suggesting that this species is continuously exposed in the studied area. These results are important for understanding the maternal offloading process and predicting PPCPs impacts throughout this species life cycle.

Protective Effect of Honey Against Zinc Oxide Nanoparticles' Toxicity in Maternal and Foetal Livers of Rat

Protective Effect of Honey Against Zinc Oxide Nanoparticles' Toxicity in Maternal and Foetal Livers of Rat

Maternal Diabetes and Postnatal High-Fat Diet on Pregnant Offspring.

Maternal diabetes-induced fetal programming predisposes offspring to type 2 diabetes, cardiovascular disease, and obesity in adulthood. However, lifelong health and disease trajectories depend on several factors and nutrition is one of the main ones. We intend to understand the role of maternal diabetes-induced fetal programming and its association with a high-fat diet during lifelong in the female F1 generation focusing on reproductive outcomes and the possible changes in physiological systems during pregnancy as well as the repercussions on the F2 generation at birth. For this, we composed four groups: F1 female pups from control (OC) or from diabetic dams (OD) and fed with standard (SD) or high-fat diet from weaning to full-term pregnancy. During pregnancy, glucose intolerance and insulin sensitivity were evaluated. In a full-term pregnancy, the maternal blood and liver were collected to evaluate redox status markers. The maternal blood, placental tissue, and fetal blood (pool) were collected to evaluate adiponectin and leptin levels. Maternal reproductive parameters were evaluated as well. Maternal diabetes and high-fat diet consumption, in isolation, were both responsible for increased infertility rates and fasting glucose levels in the F1 generation and fetal growth restriction in the F2 generation. The association of both conditions showed, in addition to those, increased lipoperoxidation in maternal erythrocytes, regardless of the increased endogenous antioxidant enzyme activities, glucose intolerance, decreased number of implantation sites and live fetuses, decreased litter, fetal and placental weight, increased preimplantation losses, and increased fetal leptin serum levels. Thus, our findings show that fetal programming caused by maternal diabetes or lifelong high-fat diet consumption leads to similar repercussions in pregnant rats. In addition, the association of both conditions was responsible for glucose intolerance and oxidative stress in the first generation and increased fetal leptin levels in the second generation. Thus, our findings show both the F1 and F2 generations harmed health after maternal hyperglycemic intrauterine environment and exposure to a high-fat diet from weaning until the end of pregnancy.

Attribution of diabetes to the development of severe liver disease in the general population.

Diabetes is associated with advanced liver disease and predicts mortality regardless of the primary aetiology of the liver disease. Even a family history of diabetes has been linked to advanced liver fibrosis in non-alcoholic fatty liver disease (NAFLD). However, the fraction of liver-related outcomes in the general population that are attributable to diabetes remains unclear. The population attributable fraction (PAF) of diabetes for liver disease as a time-dependent exposure was estimated in the Finnish FINRISK study (n=28 787) and the British Whitehall II study (n=7855). We also assessed the predictive ability of a family history of diabetes for liver-related outcomes. Incident diabetes data were from drug purchase/reimbursement and healthcare registries (FINRISK) or follow-up examinations (Whitehall II). Incident severe liver outcomes were identified through linkage with national healthcare registries. Diabetes was associated with a two-fold risk of liver-related outcomes in both the FINRISK (HR, 1.92; p< .001) and Whitehall II (HR, 2.37; p< .001) cohorts, and this remained significant after adjusting for multiple confounders. PAF analyses demonstrated that diabetes explained 12-14% of the risk for severe liver-related outcomes after 10 and 20 years of follow-up. Also, maternal diabetes increased the risk of liver-related outcomes in the FINRISK (HR, 1.43; p= .044) and Whitehall II (HR, 2.04; p= .051) cohorts. Approximately 12%-14% of severe liver-related outcomes are attributable to diabetes at the population level. The association between maternal diabetes and liver disease might suggest a mitochondrial genetic mechanism.

Butyrate increases maternal liver lipid accretion and ameliorates fetal markers of fatty liver programming

Butyrate increases maternal liver lipid accretion and ameliorates fetal markers of fatty liver programming

Hypoxia ameliorates maternal diet-induced insulin resistance during pregnancy while having a detrimental effect on the placenta.

Maternal overweight/obesity contributes significantly to the development of gestational diabetes, which causes risks to both mother and fetus and is increasing sharply in prevalence worldwide. Since hypoxia reprograms energy metabolism and can alleviate weight gain, adiposity, insulin resistance (IR), and dyslipidemia, we set out to study the potential of sustained reduced ambient oxygen tension (15% O2) during pregnancy for alleviating the detrimental effects of diet‐induced IR in C57Bl/6N mice, taking normal chow‐fed and normoxia (21% O2) groups as controls. Our data show that hypoxic intervention reduced maternal weight gain, adiposity, and adipose tissue inflammation, and ameliorated maternal glucose metabolism and IR during gestation in diet‐induced IR relative to normoxia. Where diet‐induced IR reduced maternal hemoglobin and increased serum erythropoietin levels, hypoxic intervention compensated for these changes. Diet‐induced IR reduced fetal growth in normoxia, and even more in hypoxia. Hypoxic intervention reduced liver weight gain during pregnancy in the dams with diet‐induced IR, maternal liver weight being positively associated with embryo number. In case of diet‐induced IR, the hypoxic intervention compromised placental energy metabolism and vascularization and increased end‐pregnancy placental necrosis. Altogether, these data show that although hypoxic intervention mediates several beneficial effects on maternal metabolism, the combination of it with diet‐induced IR is even more detrimental to the placental and fetal outcome than diet‐induced IR alone.

Gestational purple grape juice consumption does not change fetal ductus arteriosus constriction in Wistar rats.

Grape juice consumption may influence the early occurrence of ductal constriction during pregnancy, since the consumption of foods rich in polyphenols can be linked to the premature constriction of the ductus arteriosus. This study aimed to evaluate the effect of purple grape juice consumption during gestation on fetal ductus arteriosus closure, prostaglandin levels, and oxidative stress markers in Wistar rats. We divided 18 pregnant rats into four groups: a control group (C), a single-dose grape juice group (SDGJ), a two-dose grape juice group (TDGJ) of 7μl/g body weight per day, and an indomethacin group (I). Blood was collected on gestational day (GD) 0, 14, and 20. Prostaglandin levels were measured, and the livers and hearts were removed from the mothers and fetuses for oxidative stress analysis; histology of the fetal ductus arteriosus was performed. Prostaglandin levels (pg/ml) at GD 20 were (C:1462.10 ± 314.61); (SDGJ:987.66 ± 86.25); (TDGJ:1290.00 ± 221.57), and (I:584.75 ± 46.77). Fetal ductus arteriosus closure occurred only in the indomethacin group. Lipid peroxidation evaluated through thiobarbituric acid reactive substances (nmol/mg protein) in maternal livers was lower in the grape juice groups (C: 4.11 ± 0.76 nmol/mg protein), (SDGJ: 2.34 ± 0.36), (TDGJ: 1.52 ± 0.18), and (I: 4.20 ± 0.76). Sulfhydryls (nmol/mg protein) were lower in the TDGJ group (C:763.59 ± 61.38 nmol/mg protein), (SDGJ:978.88 ± 158.81), (TDGJ:385.32 ± 86.78), and (I:727.72 ± 49.12). Also, superoxide dismutase activity (USOD/mg protein) was higher in fetal hearts in this group: (C:5.29 ± 0.33), (SDGJ:4.48 ± 0.47), (TDGJ:7.35 ± 0.43), and (I:6.00 ± 0.18). We conclude that grape juice consumption in pregnancy does not induce ductus arteriosus closure in the fetus and presented potential antioxidant effects.

56 Vitamin and Mineral Supplementation Throughout Gestation Affects Liver Trace Mineral Status of Dam and Neonatal Calves but not Calf Morphometric Characteristics

Abstract Objectives were to evaluate the effects of feeding a vitamin and mineral supplementation (VMSUP) to heifers throughout gestation on trace mineral status of the dam and calf, calving parameters, and calf characteristics. We hypothesized that VMSUP throughout gestation would enhance mineral status in the dam and offspring at birth and positively impact calf morphometric characteristics. Thirty-one Angus-based heifers (body weight [BW]=273.7 ± 1.10 kg) were estrous synchronized, bred with female sexed semen, then were randomly assigned to either a basal diet targeting gain of 0.45 kg/d (CON; n=14) or the basal diet plus a vitamin and mineral supplement (VTM; n=17; 113 g•heifer-1•d-1). Liver biopsies were obtained from dams at breeding, d 84 and 180 of gestation, and at calving from dams and calves. Trace mineral concentrations were determined via inductively coupled plasma mass spectrometry. Calving ease, calf vigor and body weight were recorded at birth, and body measurements were recorded at 24 h after birth. Data were analyzed using the GLM Procedure of SAS using repeated measures analysis when appropriate. In maternal liver, concentrations of selenium and copper were affected by a treatment × day interaction (P &amp;lt; 0.0001), being greater (P &amp;lt; 0.001) for VTM than CON at all post-breeding timepoints and decreasing (P ≤ 0.05) from d 84 to calving; while zinc, molybdenum, manganese, and cobalt were not (P ≥ 0.20) affected by treatment. In calves, concentrations of liver selenium, copper, zinc, and cobalt were greater for VTM than CON (P &amp;lt; 0.05). Gestation length, calving distribution, ease and vigor scores, calf BW and body measurements were not affected by treatment (P = 0.278). Therefore, VTM supplementation throughout gestation affected liver trace mineral reserves of dam and calf; but did not affect calf size or any of the calving parameters evaluated. These results suggest that as gestation progresses, maternal liver mineral stores decrease to provide for the gestating calf.

Calcifediol During Pregnancy Improves Maternal and Fetal Availability of Vitamin D Compared to Vitamin D3 in Rats and Modifies Fetal Metabolism.

The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 μg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 μg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.