ESPE Abstracts (2015) 84 P-3-1251

ESPE2015 Poster Category 3 Programming & Misc. (9 abstracts)

Sexually Dimorphic Methylation of SF-1 in Rat Placenta after Gestational Exposure to BPA

Julie Fudvoye a, , Pierre Dehan b , Mehdi Liénard a , Geert Trooskens d , Arlette Gérard a , Jean-Pierre Bourguignon a, & Anne-Simone Parent a,

aNeuroendocrinology Unit, GIGA Neurosciences, University of Liège, Liège, Belgium; bLaboratory of Experimental Pathology, GIGA Cancer, University of Liège, Liège, Belgium; cPediatric Department, CHU Liège, Liège, Belgium; dDepartment of Mathematical Modelling, Statistics and Bio-informatics, Ghent, Belgium

Background: Gestational exposure to endocrine disrupting chemicals (EDCs) can impact the control of sexual differentiation by altering the hormonal environment of the foetus. Prenatal exposure to BPA, for instance could lead to disorders of sexual development. At the interface between the mother and the foetus, the placenta plays a key role in foetal programming and responds to environmental stressors in a sex specific manner. Epigenetics has appeared to be a key mechanism for regulation of gene expression in response to early life environment.

Aims and hypothesis: We hypothesised that epigenetic modifications at the level of the placenta could be involved in the potential adverse effects of BPA on sexual differentiation and development. We aimed at studying the modifications of DNA methylation in male and female placenta after gestational exposure to BPA.

Methods: Pregnant rats were exposed orally to BPA (10 mg/kg per day) from gestational day 6 (GD6) to GD18. Placenta obtained by caesarean section were harvested at GD19. Male and female placentas were identified using classical PCR for SRY expression. Genome-wide DNA micro-array analysis was performed to identify genes with increased methylation following gestational exposure to BPA.

Results: Genome-wide analysis showed that four genes exhibited significant hypermethylation in the female placenta after BPA exposure. In particular, SF-1 was hypermethylated after BPA exposure in female but not male placenta and we are currently validating the hypermethylation of the SF-1 promoter using methylation specific PCR after bisulfite treatment.

Conclusion: In conclusion, prenatal exposure to a high dose of BPA leads to changes in placental DNA methylation pattern of specific genes in a sexually dimorphic manner. SF-1, a key regulator of sexual development appears to be a good placental epigenetic biomarker of gestational exposure to BPA and could mediate the adverse effects of BPA on the reproductive system.

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