Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue.
Prenatal development is highly plastic and readily influenced by the environment. Adverse conditions have been shown to alter organ development and predispose offspring to chronic diseases, including diabetes and hypertension. Notably, it appears that the changes in glucocorticoid hormones or glucocorticoid receptor (GR) levels in peripheral tissues could play a role in the development of chronic diseases. We have previously demonstrated that in vitro fertilization (IVF) and preimplantation embryo culture is associated with growth alterations and glucose intolerance in mice. However, it is unknown if GR signaling is affected in adult IVF offspring. Here we show that GR expression is increased in inbred (C57Bl6/J) and outbred (CF-1× B6D2F1/J) blastocysts following in vitro culture and elevated levels are also present in the adipose tissue of adult male mice. Importantly, genes involved in lipolysis and triglyceride synthesis and responsive to GR were also increased in adipose tissue, indicating that increased GR activates downstream gene pathways. The promoter region of GR, previously reported to be epigenetically modified by perinatal manipulation, showed no changes in DNA methylation status. Our findings demonstrate that IVF results in a long-term change in GR gene expression in a sex- and tissue-specific manner. These changes in adipose tissues may well contribute to the metabolic phenotype in mice conceived by IVF.
1Department of Obstetrics,Gynecology and Reproductive Sciences,University of California San Francisco,San Francisco,CA,USA.
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RK
Simbulan
1Department of Obstetrics,Gynecology and Reproductive Sciences,University of California San Francisco,San Francisco,CA,USA.
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Liu
1Department of Obstetrics,Gynecology and Reproductive Sciences,University of California San Francisco,San Francisco,CA,USA.
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Feuer
2Department of Pediatrics,University of California San Francisco,San Francisco,CA,USA.
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Maltepe
1Department of Obstetrics,Gynecology and Reproductive Sciences,University of California San Francisco,San Francisco,CA,USA.
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Donjacour
1Department of Obstetrics,Gynecology and Reproductive Sciences,University of California San Francisco,San Francisco,CA,USA.
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Rinaudo
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015854:Up-Regulation
D011965:Receptors, Glucocorticoid; D003345:Corticosterone
assisted reproductive techonologies; developmental programming; glucocorticoid hormones; glucocorticoid receptor; in vitro fertilization