Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice

Abstract: Background: In utero exposure to obesity is consistently associated with increased risk of metabolic disease, obesity and cardiovascular dysfunction in later life despite the divergence of birth weight outcomes. The placenta plays a critical role in offspring development and long-term health, as it mediates the crosstalk between the maternal and fetal environments. However, its phenotypic and molecular modifications in the context of maternal obesity associated with fetal growth restriction (FGR) remain poorly understood. Methods: Using a mouse model of maternal diet-induced obesity, we investigated changes in the placental transcriptome through RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) at embryonic day (E) 19. The most differentially expressed genes (FDR < 0.05) were validated by Quantitative real-time PCR (qPCR) in male and female placentae at E19. The expression of these targets and related genes was also determined by qPCR at E13 to examine whether the observed alterations had an earlier onset at mid-gestation. Structural analyses were performed using immunofluorescent staining against Ki67 and CD31 to investigate phenotypic outcomes at both timepoints. Results: RNA-seq and IPA analyses revealed differential expression of transcripts and pathway interactions related to placental vascular development and tissue morphology in obese placentae at term, including downregulation of Muc15, Cnn1, and Acta2. Pdgfb, which is implicated in labyrinthine layer development, was downregulated in obese placentae at E13. This was consistent with the morphological evidence of reduced labyrinth zone (LZ) size, as well as lower fetal weight at both timepoints irrespective of offspring sex. Conclusions: Maternal obesity results in abnormal placental LZ development and impaired vascularization, which may mediate the observed FGR through reduced transfer of nutrients across the placenta

Impact of maternal obesity on placental transcriptome and morphology associated with fetal growth restriction in mice

Abstract: Background: In utero exposure to obesity is consistently associated with increased risk of metabolic disease, obesity and cardiovascular dysfunction in later life despite the divergence of birth weight outcomes. The placenta plays a critical role in offspring development and long-term health, as it mediates the crosstalk between the maternal and fetal environments. However, its phenotypic and molecular modifications in the context of maternal obesity associated with fetal growth restriction (FGR) remain poorly understood. Methods: Using a mouse model of maternal diet-induced obesity, we investigated changes in the placental transcriptome through RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) at embryonic day (E) 19. The most differentially expressed genes (FDR < 0.05) were validated by Quantitative real-time PCR (qPCR) in male and female placentae at E19. The expression of these targets and related genes was also determined by qPCR at E13 to examine whether the observed alterations had an earlier onset at mid-gestation. Structural analyses were performed using immunofluorescent staining against Ki67 and CD31 to investigate phenotypic outcomes at both timepoints. Results: RNA-seq and IPA analyses revealed differential expression of transcripts and pathway interactions related to placental vascular development and tissue morphology in obese placentae at term, including downregulation of Muc15, Cnn1, and Acta2. Pdgfb, which is implicated in labyrinthine layer development, was downregulated in obese placentae at E13. This was consistent with the morphological evidence of reduced labyrinth zone (LZ) size, as well as lower fetal weight at both timepoints irrespective of offspring sex. Conclusions: Maternal obesity results in abnormal placental LZ development and impaired vascularization, which may mediate the observed FGR through reduced transfer of nutrients across the placenta

Differential Long-Chain Polyunsaturated Fatty Acids Status and Placental Transport in Adolescent Pregnancies

Adolescent pregnancy increases risk of adverse perinatal outcomes. Placental delivery of long-chain polyunsaturated fatty acids (LCPUFA) is essential for fetal growth and development. In this pilot study, we aimed to assess maternal and fetal status of fatty acids (FA) measured at birth and the expression of key genes involved in FA uptake, transport and metabolism in the placenta of fifteen adolescents and fifteen adults. FA were quantified by gas-liquid chromatography. Placental expression of FA transporters was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and peroxisome proliferator-activated receptor gamma (PPARγ) was quantified by Western Blot. Adolescents had lower docosahexaenoic acid (DHA, 22:6 n-3) and total n-3 FA levels in maternal erythrocytes and placenta, but these were not different in fetal erythrocytes. Arachidonic acid (AA, 20:4 n-6) concentration was increased in placenta but lower in fetal circulation. Plasma membrane fatty acid binding protein (FABPpm) and fatty acid transport protein (FATP) 4 mRNA expressions were not different, however FATP1, fatty acid translocase (FAT/CD36) and fatty acid binding protein 3 (FABP3) mRNA and PPARγ protein levels were decreased in placenta of adolescents. Despite significant downregulation of FATP1, CD36 and FABP3, there was only a modest decrease in LCPUFA (10%) and AA (12%) and no difference in DHA content in cord blood, suggesting that FA transfer to the fetus was partially protected by other factors in adolescents from this cohort

The Mothers, Infants, and Lactation Quality (MILQ) Study:A Multi-Center Collaboration

Little valid information is available on human milk nutrient concentrations, especially for micronutrients (MNs), and there are no valid reference values (RVs) across lactation. In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 mo postpartum. Well-nourished, unsupplemented women in Bangladesh, Brazil, Denmark, and The Gambia (n = 250/site) were recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and their infants are collected identically at 3 visits (1–3.49, 3.5–5.99, 6.0–8.49 mo postpartum). Milk analyses include macronutrients, selected vitamins, trace elements and minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. We measure milk volume; maternal and infant diets, anthropometry, and morbidity; infant development, maternal genome, and the infant and maternal microbiome. RVs will be constructed based on methods for the WHO Child Growth Standards and the Intergrowth-21st Project. This trial was registered at clinical trials.gov as NCT03254329