Effect of Overfeeding Shetland Pony Mares on Embryonic Glucose and Lipid Accumulation, and Expression of Imprinted Genes

Abstract

Maternal overfeeding is associated with disturbances in early embryonic epigenetic reprogramming, leading to altered expression of imprinted genes and nutrient transporters, which can affect both fetal and placental development and have lasting effects on the health of resulting offspring. To examine how maternal overfeeding affects the equine embryo, Shetland pony mares were fed either a high-energy (HE: 200% of net energy requirements) or maintenance (control) diet. Mares from both groups were inseminated, and day-seven embryos were recovered and transferred to recipients from the same or the alternate group. The expression of a panel of imprinted genes, glucose and amino acid transporters, and DNA methyltransferases (DNMTs) were determined in conceptus membranes after recovery on day 28 of gestation (late pre-implantation phase). The expression of nutrient transporters was also assessed in endometrium recovered from recipient mares immediately after conceptus removal. In addition, glucose uptake by day-28 extra-embryonic membranes, and lipid droplet accumulation in day-seven blastocysts were assessed. Maternal overfeeding resulted in elevated expression of imprinted genes (IGF2, IGF2R, H19, GRB10, PEG10 and SNRPN), DNMTs (DNMT1 and DNMT3B), glucose (SLC2A1), fructose (SLC2A5) and amino acid (SLC7A2) transporters following ET from an HE to a control mare. Expression of amino acid transporters (SLC1A5 and SLC7A1) was also elevated in the endometrium after ET from HE to control. Maternal overfeeding did not affect lipid droplet accumulation in blastocysts, or glucose uptake by day-28 membranes. It remains to be seen whether the alterations in gene expression are maintained throughout gestation and into postnatal life.

Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor‐enriched diet

“…The likelihood of accidental fetal alcohol exposure during preimplantation is substantial considering that human chorionic gonadotropin (i.e., the hormone detected by pregnancy tests) is only produced after implantation of the embryo, 72 that 40% of pregnancies are unplanned, 73 and that there is an increasing rate of alcohol consumption and binge drinking behavior among women of reproductive age, [74][75][76][77] possibly even more so since the COVID-19 pandemic. 78 During preimplantation, the embryo undergoes reprogramming of epigenetic modifications, notably DNA methylation, which is crucial for normal gene expression regulation during development [79][80][81][82] and is particularly vulnerable to unfavorable in utero environments, 83 for example, assisted reproductive technologies, [84][85][86][87][88] nutritional imbalances, [89][90][91] or exposures to chemical compounds (e.g. insecticides) 92 and alcohol.…”