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Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue

Published online by Cambridge University Press:  29 October 2015

R. K. Simbulan ,
X. Liu ,
S. K. Feuer ,
E. Maltepe ,
A. Donjacour  and
P. Rinaudo
R. K. Simbulan
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA
X. Liu
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA
S. K. Feuer
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA
E. Maltepe
Affiliation:
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
A. Donjacour
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA Department of Anatomy, University of California San Francisco, San Francisco, CA, USA
P. Rinaudo*
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA
*
*Address for correspondence: P. Rinaudo, Division of Reproductive Endocrinology and Infertility, 513 Parnassus Ave, HSW 1463E San Francisco, CA 94143, USA. (Email [email protected])
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Abstract

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.

Keywords

assisted reproductive techonologiesdevelopmental programmingglucocorticoid hormonesglucocorticoid receptorin vitro fertilization
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 7 , Issue 1: Themed Issue: The Gut Microbiome and Immunity: How it is Shaped by Early Life , February 2016 , pp. 73 - 82
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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