Exposure to maternal obesity alters gene expression in the preimplantation ovine conceptus

Abstract

BackgroundEmbryonic and fetal exposure to maternal obesity causes several maladaptive morphological and epigenetic changes in exposed offspring. The timing of these events is unclear, but changes can be observed even after a short exposure to maternal obesity around the time of conception. The hypothesis of this work is that maternal obesity influences the ovine preimplantation conceptus early in pregnancy, and this exposure will affect gene expression in embryonic and extraembryonic tissues.ResultsObese and lean ewe groups were established by overfeeding or normal feeding, respectively. Ewes were then bred to genetically similar rams. Conceptuses were collected at day 14 of gestation. Morphological assessments were made, conceptuses were sexed by genomic PCR analysis, and samples underwent RNA-sequencing analysis. While no obvious morphological differences existed between conceptuses, differentially expressed genes (≥ 2-fold; ≥ 0.2 RPKM; ≤ 0.05 FDR) were detected based on maternal obesity exposure (n = 21). Also, differential effects of maternal obesity were noted on each conceptus sex (n = 347). A large portion of differentially expressed genes were associated with embryogenesis and placental development.ConclusionsFindings reveal that the preimplantation ovine conceptus genome responds to maternal obesity in a sex-dependent manner. The sexual dimorphism in response to the maternal environment coupled with changes in placental gene expression may explain aberrations in phenotype observed in offspring derived from obese females.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5120-0) contains supplementary material, which is available to authorized users.

Diet‐induced maternal obesity impacts feto‐placental growth and induces sex‐specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice

“…The explanation for the sex‐specific effects on fetal development and placental phenotype in our control and diet‐induced obese mouse dams are unclear. However, these could originate very early, as sex defines the cellular responses of murine embryonic cells to stressors and hormones in vitro, 59 as well as the expression of genes regulating feto‐placental formation in pre‐implantation sheep and mouse embryos exposed to maternal obesity in vivo 60,61 . Moreover, placental defects persist in mice when embryos are transferred from obese to lean mouse dams 62 .…”

“…However, these could originate very early, as sex defines the cellular responses of murine embryonic cells to stressors and hormones in vitro, 59 as well as the expression of genes regulating feto‐placental formation in pre‐implantation sheep and mouse embryos exposed to maternal obesity in vivo. 60 , 61 Moreover, placental defects persist in mice when embryos are transferred from obese to lean mouse dams. 62 However, whatever the mechanisms involved, sex‐dependent changes in feto‐placental phenotype identified in the current study may have relevance for understanding the disparities between male versus female offspring growth and metabolic outcomes that have been reported in women with metabolic problems, including obesity and dysglycemia, 53 as well as in animal models fed obesogenic diets during gestation.…”