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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Cholesterol metabolism in rabbit blastocysts under maternal diabetes

S. Mareike Pendzialek A C , Maria Schindler A , Torsten Plösch B , Jacqueline Gürke A , Elisa Haucke A , Stefanie Hecht A , Bernd Fischer A and Anne Navarrete Santos A
+ Author Affiliations
- Author Affiliations

A Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Grosse Steinstr. 52, 06108 Halle (Saale), Germany.

B Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 Groningen, The Netherlands.

C Corresponding author. Email: mareike.pendzialek@medizin.uni-halle.de

Reproduction, Fertility and Development 29(10) 1921-1931 https://doi.org/10.1071/RD15542
Submitted: 23 December 2015  Accepted: 24 October 2016   Published: 6 December 2016

Abstract

In the rabbit reproductive model, maternal experimentally induced insulin-dependent diabetes mellitus (expIDD) leads to accumulation of lipid droplets in blastocysts. Cholesterol metabolism is a likely candidate to explain such metabolic changes. Therefore, in the present study we analysed maternal and embryonic cholesterol concentrations and expression of related genes in vivo (diabetic model) and in vitro (embryo culture in hyperglycaemic medium). In pregnant expIDD rabbits, the serum composition of lipoprotein subfractions was changed, with a decrease in high-density lipoprotein cholesterol and an increase in very low-density lipoprotein cholesterol; in uterine fluid, total cholesterol concentrations were elevated. Expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), very low-density lipoprotein receptor (VLDLR), sterol regulatory element binding transcription factor 2 (SREBF2), insulin-induced gene-1 (INSIG1) and cholesterol 7α-hydroxylase (CYP7A1) mRNA was decreased in the liver and low-density lipoprotein receptor (LDLR) mRNA expression was decreased in the adipose tissue of diabetic rabbits. In embryos from diabetic rabbits, the mean (± s.e.m.) ratio of cholesterol concentrations in trophoblasts to embryoblasts was changed from 1.27 ± 2.34 (control) to 0.88 ± 3.85 (expIDD). Rabbit blastocysts expressed HMGCR, LDLR, VLDLR, SREBF2 and INSIG1 but not CYP7A1, without any impairment of expression as a result of maternal diabetes. In vitro hyperglycaemia decreased embryonic HMGCR and SREBF2 transcription in rabbit blastocysts. The findings of the present study show that a diabetic pregnancy leads to distinct changes in maternal cholesterol metabolism with a minor effect on embryo cholesterol metabolism.

Additional keywords: development, embryo, lipid, pregnancy, preimplantation.


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