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.
Publication Date: 2021-08-26 PubMed ID: 34573470PubMed Central: PMC8470267DOI: 10.3390/ani11092504Google Scholar: Lookup
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- Journal Article
Summary
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This research studied how overfeeding Shetland pony mares affects the expression of genetic material and nutrient accumulation in early-stage embryos. The results showed that overfeeding led to elevated expression of certain genes and nutrient transporters, but it did not affect the accumulation of fat in the embryos or glucose uptake by the embryos’ membranes.
Research Objective and Methodology
- The objective of this study was to understand how maternal overfeeding influences the equine embryo, especially in terms of epigenetic reprogramming – the process by which gene expression is altered without changing the DNA sequence.
- To achieve this, Shetland pony mares were split into two dietary groups: those receiving a high-energy (200% of net energy requirements) diet, and those receiving a maintenance (control) diet.
- Mares from both groups were inseminated, and embryos from the seventh day were collected and transferred to recipients within the same or different dietary group.
Data Collection
- On the 28th day of gestation, the expression of a set of imprinted genes, glucose and amino acid transporters, and DNA methyltransferases (enzymes that transfer methyl groups to DNA molecules) were measured in the conceptuses’ membranes.
- The study team noted nutrient transporters expression in the endometrium (inner lining of the uterus) after the conceptus was removed.
- They also measured glucose uptake by the extra-embryonic membranes on day 28, and fat accumulation in the blastocysts (early-stage embryos) on day seven.
Findings
- Overfeeding led to increased expression of imprinted genes, DNA methyltransferases, and glucose, fructose, and amino acid transporters when embryos were transferred from a high-energy diet mare to a control diet mare.
- No noticeable effects were found on fat accumulation in day seven blastocysts or glucose uptake by the membranes on day 28 due to overfeeding.
Conclusion
- Maternal overfeeding impacts the genetic and nutrient transport expressions in horse embryos, potentially influencing their development and the health of the resulting offspring.
- The study doesn’t confirm if these changes in genetic expression persist throughout gestation or into postnatal life, indicating a direction for future research.
Cite This Article
APA
D' Fonseca NMM, Gibson CME, van Doorn DA, Roelfsema E, de Ruijter-Villani M, Stout TAE.
(2021).
Effect of Overfeeding Shetland Pony Mares on Embryonic Glucose and Lipid Accumulation, and Expression of Imprinted Genes.
Animals (Basel), 11(9).
https://doi.org/10.3390/ani11092504 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
Grant Funding
- 317146 / FP7 People: Marie-Curie Actions
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 40 references
- Gillman MW. Developmental Origins of Health and Disease. N. Engl. J. Med. 2005;353:1848–1850.
- Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome. J. Vet. Intern. Med. 2018;33:335–349.
- Robles M, Nouveau E, Gautier C, Mendoza L, Dubois C, Dahirel M, Lagofun B, Aubrière M-C, Lejeune J-P, Caudron I. Maternal obesity increases insulin resistance, low-grade inflammation and osteochondrosis lesions in foals and yearlings until 18 months of age. PLoS ONE 2018;13:e0190309.
- Wilkins JF. Genomic imprinting and methylation: Epigenetic canalization and conflict. Trends Genet. 2005;21:356–365.
- Faulk C, Dolinoy DC. Timing is everything. Epigenetics 2011;6:791–797.
- Betteridge KJ, Eaglesome MD, Mitchell D, Flood PF, Beriault R. Development of horse embryos up to twenty two days after ovulation: Observations on fresh specimens. J. Anat. 1982;135:191–209.
- Seisenberger S, Peat J, Hore T, Santos F, Dean W, Reik W. Reprogramming DNA methylation in the mammalian life cycle: Building and breaking epigenetic barriers. Philos. Trans. R. Soc. B Biol. Sci. 2013;368:20110330.
- Chmurzynska A. Fetal programming: Link between early nutrition, DNA methylation, and complex diseases. Nutr. Rev. 2010;68:87–98.
- Fowden A, Coan P, Angiolini E, Burton G, Constancia M. Imprinted genes and the epigenetic regulation of placental phenotype. Prog. Biophys. Mol. Biol. 2011;106:281–288.
- Fowden A, Sibley C, Constancia M, Reik W. Imprinted Genes, Placental Development and Fetal Growth. Horm. Res. Paediatr. 2006;65:50–58.
- Lau MM, Stewart C, Liu Z, Bhatt H, Rotwein P. Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev. 1994;8:2953–2963.
- Charalambous M, Smith FM, Bennett B, Crew TE, Mackenzie F, Ward A. Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism. Proc. Natl. Acad. Sci. USA 2003;100:8292–8297.
- Moore GE, Ishida M, Demetriou C, Al-Olabi L, Leon LJ, Thomas AC, Abu-Amero S, Frost JM, Stafford JL, Chaoqun Y. The role and interaction of imprinted genes in human fetal growth. Philos. Trans. R. Soc. B Biol. Sci. 2015;370:20140074.
- Ono R, Nakamura K, Inoue K, Naruse M, Usami T, Wakisaka-Saito N, Hino T, Suzuki-Migishima R, Ogonuki N, Miki H. Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nat. Genet. 2005;38:101–106.
- Sasson IE, Vitins AP, Mainigi M, Moley KH, Simmons RA. Pre-gestational vs gestational exposure to maternal obesity differentially programs the offspring in mice. Diabetologia 2015;58:615–624.
- Sferruzzi-Perri AN, Vaughan OR, Haro M, Cooper WN, Musial B, Charalambous M, Pestana D, Ayyar S, Ferguson-Smith AC, Burton GJ. An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J. 2013;27:3928–3937.
- Carter AM, Enders AC. The Evolution of Epitheliochorial Placentation. Annu. Rev. Anim. Biosci. 2013;1:443–467.
- Gibson C, De Ruijter-Villani M, Rietveld J, Stout TA. Expression of glucose transporters in the endometrium and early conceptus membranes of the horse. Placenta 2018;68:23–32.
- Filant J, Spencer TE. Uterine glands: Biological roles in conceptus implantation, uterine receptivity and decidualization. Int. J. Dev. Biol. 2014;58:107–116.
- Zavy MT, Bazer FW, Sharp DC, Wilcox CJ. Uterine Luminal Proteins in the Cycling Mare. Biol. Reprod. 1979;20:689–698.
- Gibson C, De Ruijter-Villani M, Rietveld J, Stout TAE. Amino acid transporter expression in the endometrium and conceptus membranes during early equine pregnancy. Reprod. Fertil. Dev. 2018;30:1675.
- Song L, Sun B, Boersma GJ, Cordner ZA, Yan J, Moran TH, Tamashiro KL. Prenatal high-fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat. Obesity 2017;25:909–919.
- Rosario FJ, Kanai Y, Powell T, Jansson T. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity 2015;23:1663–1670.
- Fonseca NMMD, Gibson CME, Van Doorn DA, De Ruijter-Villani M, Stout TAE, Roelfsema E. Effect of long-term overfeeding of a high-energy diet on glucose tolerance in Shetland pony mares. J. Vet. Intern. Med. 2020;34:1339–1349.
- Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet. J. 1983;15:371–372.
- Bamford N, Potter S, Harris P, Bailey S. Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score. Domest. Anim. Endocrinol. 2014;47:101–107.
- Carter RA, McCutcheon LJ, George LA, Smith TL, Frank N, Geor RJ. Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses. Am. J. Vet. Res. 2009;70:1250–1258.
- Stout TAE. Equine embryo transfer: Review of developing potential. Equine Vet. J. 2006;38:467–478.
- Clark KE, Squires EL, McKinnon AO, Seidel GE. Viability of Stored Equine Embryos. J. Anim. Sci. 1987;65:534–542.
- Gibson C, De Ruijter-Villani M, Stout TA. Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes. Placenta 2017;57:175–182.
- de Ruijter-Villani M, van Boxtel PR, Stout TA. Fibroblast growth factor-2 expression in the preimplantation equine conceptus and endometrium of pregnant and cyclic mares. Theriogenology 2013;80:979–989.
- Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3:research0034.1.
- Blodgett AB, Kothinti RK, Kamyshko I, Petering DH, Kumar S, Tabatabai NM. A Fluorescence Method for Measurement of Glucose Transport in Kidney Cells. Diabetes Technol. Ther. 2011;13:743–751.
- Sessions-Bresnahan DR, Schauer K, Heuberger AL, Carnevale EM. Effect of obesity on the preovulatory follicle and lipid fingerprint of equine oocytes. Biol. Reprod. 2016;94:15.
- Sessions-Bresnahan DR, Heuberger AL, Carnevale EM. Obesity in mares promotes uterine inflammation and alters embryo lipid fingerprints and homeostasis. Biol. Reprod. 2018;99:761–772.
- Fonseca NMMD, Gibson CME, Hummel I, van Doorn DA, Roelfsema E, Stout TA, Broek JVD, de Ruijter-Villani M. Overfeeding Extends the Period of Annual Cyclicity but Increases the Risk of Early Embryonic Death in Shetland Pony Mares. Animals 2021;11:361.
- Nomura Y, Lambertini L, Rialdi A, Lee M, Ba EYM, Grabie M, Bs IM, Huynh N, Finik J, Davey M. Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity. Reprod. Sci. 2013;21:131–137.
- Takao Y, Akazawa S, Matsumoto K, Takino H, Akazawa M, Trocino RA, Maeda Y, Okuno S, Kawasaki E, Uotani S. Glucose transporter gene expression in rat conceptus during high glucose culture. Diabetologia 1993;36:696–706.
- Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, Wu X, Yu Y, Amlal H, Seidler U. Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension. J. Biol. Chem. 2009;284:5056–5066.
- Cleal JK, Lofthouse EM, Sengers BG, Lewis RM. A systems perspective on placental amino acid transport. J. Physiol. 2018;596:5511–5522.
Citations
This article has been cited 2 times.- Li T, Jin Y, Wu J, Ren Z. Beyond energy provider: multifunction of lipid droplets in embryonic development. Biol Res 2023 Jul 12;56(1):38.
- Breton-Larrivée M, Elder E, Legault LM, Langford-Avelar A, MacFarlane AJ, McGraw S. Mitigating the detrimental developmental impact of early fetal alcohol exposure using a maternal methyl donor-enriched diet. FASEB J 2023 Apr;37(4):e22829.
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