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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P288 | DOI: 10.1530/repabs.1.P288

Periconceptional alcohol exposure programs sex specific hyperinsulinemia possibly through dysregulation of placental O-linked glycosylation

Emelie M Gardebjer, Kathryn McMahon, Karen M Moritz & Marie Pantaleon

The University of Queensland, St Lucia, Queensland, Australia.

Introduction: Exposure to an adverse environment around the time of conception can program adult onset disease although mechanisms involved are unclear. Recently we showed that periconceptional alcohol (PC:EtOH) consumption causes placental stress demonstrated by elevated levels of 11βHSD-2, and sex-specific increases in placental glucose transporters and glycogen accumulation. O-linked-N-acetylglucosamine transferase (OGT), an X-linked gene product, responsible for O-linked glycosylation (O-GlcNAcylation), has also been identified as a placental biomarker of maternal stress. Indeed, the ability to respond to stress via O-GlcNAcylation is linked with cellular survival. Moreover, dysregulation of O-GlcNAcylation is also implicated in metabolic disease. We examined OGT levels in placentas following PC:EtOH-exposure and determined postnatal metabolic outcomes.

Materials and methods: Sprague–Dawley rats were exposed to an EtOH containing diet (12.5%, n=12/group) during the PC period (E-4 to E4). Placentas were collected from a subset of dams on E20 and levels of OGT were assessed via western blotting. Fasting glucose and insulin concentrations were measured in six month offspring of a different subset of dams and the HOMA-IR-index calculated.

Results and discussion: PC:EtOH-exposure resulted in fetal growth restriction. OGT levels were specifically elevated in the spongiotrophoblast in placentas from female (P<0.05), but not male fetuses following PC:EtOH-exposure, while OGT levels in the labyrinth were unchanged in placentas from both sexes. Interestingly, insulin levels (P<0.05) and HOMA-IR-index (P<0.05) were elevated in male offspring following PC:EtOH-exposure. Our results suggest that sex-specific alterations in placental OGT levels in response to PC:EtOH-exposure may act to protect the female fetus from hyperinsulinemia in later life.

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