ECE2020 Audio ePoster Presentations Reproductive and Developmental Endocrinology (79 abstracts)
The vulnerability of prepubertal ovarian steroidogenesis to AhR-mediated TCDD action occurs during a time-restricted window in mice
Marie Devillers 1 , Florence Petit 1 , Frank Giton 2 , Charlotte François 1 , Ludmila Juricek 3 , Xavier Coumoul 3 , Solange Magre 1 , Joëlle Cohen-Tannoudji 1 & Celine Guigon 1
1Université de Paris, CNRS, INSERM, Biologie Fonctionnelle et Adaptative UMR 8251, Physiologie de l’Axe Gonadotrope U1133, Paris, France; 2AP-HP, Pôle Biologie-Pathologie Henri Mondor, Créteil, France, INSERM IMRB U955 eq07, Créteil, France; 3INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, Paris, France
Background: In females, timing of puberty and fertility require estradiol (E2) action at the infantile and late juvenilestages and are tightly influenced by environmental cues. A regulator of intra-ovarian E2 synthesis during reproductive life is the aryl hydrocarbon receptor (AhR). However, its action on E2 synthesis and its capacity to mediate the effect of endocrine disrupting chemicals (EDC)s has not been thoroughly evaluated during the prepubertal period.
Objectives: Determining intrinsic and EDC-induced activity of AhR on E2 synthesis at critical prepubertal stages for reproductive function programming.
Methods: The intra-ovarian expression of components of the steroidogenesis pathway, prototypical AhR target genes (Ahrr, Cyp1a1) and E2 contents were examined in the Ahrknockout (Ahr–/–) mouse at the neonatal (7 days postnatal (dpn)), infantile (14 dpn), early (21 dpn) and late juvenile stages (28 dpn) and in the highly dioxine sensitive C57Bl/6J mouse strain treated at 14 or 28 dpn with AhR ligands, FICZ and TCDD. The expression of AhR was analyzed in both mouse and human ovaries.
Results: Intrinsic AhR pathway became active only at the end of the prepubertal period, as revealed in Ahr–/– mice versus Ahr +/ + miceby the down-regulation in the relative intra-ovarian contents of E2, Cyp19a1 aromatase and Ahrrtranscripts exclusivelyat 28 dpn. AhR activation by exogenous ligands could occur at any stage, as suggested by TCDD-induced Ahrr and Cyp1a1 expression at both 14 and 28 dpn, but itimpaired Cyp19a1 expression and E2 synthesis only at 28 dpn. Although AhR is detected in the ovary throughout the prepubertal period, its nuclear localization, reflecting its activity, in granulosa cells responsible for E2 synthesis, was weak at the infantile stage.
Discussion: AhR regulation of E2 synthesis would start at the approach of puberty. We propose that AhR-mediated EDC action specifically at this stage could be particularly detrimental for reproductive function programming.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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