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

Nicky M M D’ Fonseca,Marta De Ruijter-Villani,Tom A E Stout,Ellen Roelfsema,Charlotte M E Gibson,David A Van Doorn

doi:10.3390/ani11092504

Nicky M M D’ Fonseca, Marta De Ruijter-Villani + Show 4 more

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https://doi.org/10.3390/ani11092504

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Journal: Animals	Publication Date: Aug 26, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Utrecht University

Abstract

Simple SummaryIn pregnant individuals, maternal overnutrition is associated with disturbances in the expression of specific genes and nutrient transporters in the early embryo, 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 several genes, nutrient transporters and DNA methyltransferases (DNMTs; play an important role in regulating gene expression) were determined in extra-embryonic membranes after recovery on day 28 of gestation. The expression of nutrient transporters was also assessed in endometrium recovered from recipient mares immediately after embryo removal. In addition, glucose uptake by day-28 extra-embryonic membranes, and lipid droplet accumulation in day-seven embryos were assessed. Maternal overfeeding resulted in elevated expression of several genes, DNMTs and nutrient transporters following embryo transfer from an HE to a control mare. The expression of two amino acid transporters was also elevated in the endometrium after embryo transfer from HE to control. Maternal overfeeding did not affect lipid droplet accumulation in day-seven embryos, or glucose uptake by membranes of day-28 embryos. It remains to be seen whether the alterations in gene expression are maintained throughout gestation and into postnatal life.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.

Highlights

Research into the developmental origins of health and disease (DOHaD) has revealed the far-reaching effects that both maternal under- and overnutrition can have on the epigenome of the developing embryo and fetus, with the potential to influence susceptibility to lifestyle-related diseases into adulthood [1].Overfeeding is an increasingly common issue in horses and is currently a topic of interest primarily because of its association with an increased risk of metabolic syndrome [2] in the individual overfed animal
This study aimed to examine the effect of maternal overfeeding during the periconthe extra-embryonic membranes and lipid accumulation in blastocyst stage embryos and into the extra-embryonic membranes and lipid accumulation in blastocyst stage embryos ception onglucose nutrient handling and gene expression in Shetland the of and amino acid imprinted transporters in the endometrium of thepony recipient andexpression the period expression of glucose and amino acid transporters in the endometrium of thepreremare
We examined the actual glucose uptake all cases, this effect took the form of significantly higher expression when embryos were into the extra-embryonic membranes and lipid accumulation in blastocyst stage embryos transferred from an donor to a control recipient mare

Summary

Introduction

Research into the developmental origins of health and disease (DOHaD) has revealed the far-reaching effects that both maternal under- and overnutrition can have on the epigenome of the developing embryo and fetus, with the potential to influence susceptibility to lifestyle-related diseases (e.g., hypertension and type 2 diabetes) into adulthood [1].Overfeeding is an increasingly common issue in horses and is currently a topic of interest primarily because of its association with an increased risk of metabolic syndrome [2] in the individual overfed animal. Research into the developmental origins of health and disease (DOHaD) has revealed the far-reaching effects that both maternal under- and overnutrition can have on the epigenome of the developing embryo and fetus, with the potential to influence susceptibility to lifestyle-related diseases (e.g., hypertension and type 2 diabetes) into adulthood [1]. A less well-investigated area of study is the possibility for transgenerational effects and, in particular, whether maternal overfeeding or obesity in the periconception period affects the epigenome of the horse embryo and may predispose the offspring to the development of metabolic or orthopedic disease later in life [3]. In other species, maternal nutrition has been shown to influence epigenetic reprogramming, with the potential for lifelong effects on gene expression in the offspring, including increased susceptibility to complex, lifestyle related diseases in adulthood [8]

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