Dataset Information

Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep.

ABSTRACT: This study aimed to determine whether exposure of the oocyte and/or embryo to maternal undernutrition results in the later programming of insulin action in the liver and factors regulating gluconeogenesis. To do this, we collect livers from singleton and twin fetal sheep that were exposed to periconceptional (PCUN; -60 to 7 days) or preimplantation (PIUN; 0-7 days) undernutrition at 136-138 days of gestation (term = 150 days). The mRNA and protein abundance of insulin signaling and gluconeogenic factors were then quantified using qRT-PCR and Western blotting, respectively, and global microRNA expression was quantified using deep sequencing methodology. We found that hepatic PEPCK-C mRNA (P < 0.01) and protein abundance and the protein abundance of IRS-1 (P < 0.01), p110? (P < 0.05), PTEN (P < 0.05), CREB (P < 0.01), and pCREB (Ser(133); P < 0.05) were decreased in the PCUN and PIUN singletons. In contrast, hepatic protein abundance of IRS-1 (P < 0.01), p85 (P < 0.01), p110? (P < 0.001), PTEN (P < 0.01), Akt2 (P < 0.01), p-Akt (Ser(473); P < 0.01), and p-FOXO-1 (Thr24) (P < 0.01) was increased in twins. There was a decrease in PEPCK-C mRNA (P < 0.01) but, paradoxically, an increase in PEPCK-C protein (P < 0.001) in twins. Both PCUN and PIUN altered the hepatic expression of 23 specific microRNAs. We propose that the differential impact of maternal undernutrition in the presence of one or two embryos on mRNAs and proteins involved in the insulin signaling and gluconeogenesis is explained by changes in the expression of a suite of specific candidate microRNAs.

SUBMITTER: Lie S

PROVIDER: S-EPMC4010656 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep.

Lie Shervi S Morrison Janna L JL Williams-Wyss Olivia O Suter Catherine M CM Humphreys David T DT Ozanne Susan E SE Zhang Song S MacLaughlin Severence M SM Kleemann David O DO Walker Simon K SK Roberts Claire T CT McMillen I Caroline IC

American journal of physiology. Endocrinology and metabolism 20140204 9

This study aimed to determine whether exposure of the oocyte and/or embryo to maternal undernutrition results in the later programming of insulin action in the liver and factors regulating gluconeogenesis. To do this, we collect livers from singleton and twin fetal sheep that were exposed to periconceptional (PCUN; -60 to 7 days) or preimplantation (PIUN; 0-7 days) undernutrition at 136-138 days of gestation (term = 150 days). The mRNA and protein abundance of insulin signaling and gluconeogenic ...[more]

PMID: 24496309

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Project description:BackgroundBiologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.ObjectiveTo determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.Search strategyPubMed and EMBASE databases were searched through January 1998-July 2021.Selection criteriaPeer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data.Data collection and analysisTwo authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence.Main resultsThirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I2 = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I2 = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I2 = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I2 = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I2 = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I2 = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I2 = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I2 = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I2 = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I2 = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I2 = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I2 = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low.ConclusionWe demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.

Project description:Key pointsFetal growth restriction induces a haemodynamic response that aims to maintain blood flow to vital organs such as the brain, in the face of chronic hypoxaemia Maternal sildenafil treatment impairs the hypoxaemia-driven haemodynamic response and potentially compromises fetal development.AbstractInadequate substrate delivery to a fetus results in hypoxaemia and fetal growth restriction (FGR). In response, fetal cardiovascular adaptations redirect cardiac output to essential organs to maintain oxygen delivery and sustain development. However, FGR infants remain at risk for cardiovascular and neurological sequelae. Sildenafil citrate (SC) has been examined as a clinical therapy for FGR, but also crosses the placenta and may exert direct effects on the fetus. We investigated the effects of maternal SC administration on maternal and fetal cardiovascular physiology in growth-restricted fetal sheep. Fetal sheep (0.7 gestation) underwent sterile surgery to induce growth restriction by single umbilical artery ligation (SUAL) or sham surgery (control, AG). Fetal catheters and flow probes were implanted to measure carotid and femoral arterial blood flows. Ewes containing SUAL fetuses were randomized to receive either maternal administration of saline or SC (36 mg i.v. per day) beginning 4 days after surgery, and continuing for 20 days. Physiological recordings were obtained throughout the study. Antenatal SC treatment reduced body weight by 32% and oxygenation by 18% in SUAL compared to AG. SC did not alter maternal or fetal heart rate or blood pressure. Femoral blood flow and peripheral oxygen delivery were increased by 49% and 30% respectively in SUALSC compared to SUAL, indicating impaired cardiovascular adaptation to chronic hypoxaemia. Antenatal SC directly impairs the fetal haemodynamic response to chronic hypoxaemia. Consideration of the consequences upon the fetus should be paramount when administering interventions to the mother during pregnancy.

Project description:BackgroundWe have shown recently that maternal undernutrition (UN) advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress.Methodology/principal findingsOur study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone.ConclusionsWe propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of maternal UN potentially contributing to premature ovarian ageing in offspring.

Dataset Information

Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep.

Publications

Impact of embryo number and maternal undernutrition around the time of conception on insulin signaling and gluconeogenic factors and microRNAs in the liver of fetal sheep.

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