title: Systemic compensatory response to neonatal estradiol exposure does not prevent depletion of the oocyte pool in the rat.
abstract: The formation of ovarian follicles is a finely tuned process that takes place within a narrow time-window in rodents. Multiple factors and pathways have been proposed to contribute to the mechanisms triggering this process but the role of endocrine factors, especially estrogens, remains elusive. It is currently hypothesized that removal from the maternal hormonal environment permits follicle formation at birth. However, experimentally-induced maintenance of high 17β-estradiol (E2) levels leads to subtle, distinct, immediate effects on follicle formation and oocyte survival depending on the species and dose. In this study, we examined the immediate effects of neonatal E2 exposure from post-natal day (PND) 0 to PND2 on the whole organism and on ovarian follicle formation in rats. Measurements of plasma E2, estrone and their sulfate conjugates after E2 exposure showed that neonatal female rats rapidly acquire the capability to metabolize and clear excessive E2 levels. Concomitant modifications to the mRNA content of genes encoding selected E2 metabolism enzymes in the liver and the ovary in response to E2 exposure indicate that E2 may modify the neonatal maturation of these organs. In the liver, E2 treatment was associated with lower acquisition of the capability to metabolize E2. In the ovary, E2 depleted the oocyte pool in a dose dependent manner by PND3. In 10 µg/day E2-treated ovaries, apoptotic oocytes were observed in newly formed follicles in addition to areas of ovarian cord remodeling. At PND6, follicles without any visible oocyte were present and multi-oocyte follicles were not observed. Our study reveals a major species-difference. Indeed, neonatal exposure to E2 depletes the oocyte pool in the rat ovary, whereas in the mouse it is well known to increase oocyte survival.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1085 Institut de Recherche en Santé Environnement et Travail, Institut Fédératif de Recherche 140, Université de Rennes 1, Rennes, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Chalmey
authors.forename: Frank
authors.initials: F
authors.lastname: Giton
authors.affiliation: AP-HP, Hôpital H. Mondor - A. Chenevier, service de Biochimie et de Génétique, Créteil, France ; Institut National de la Santé et de la Recherche Médicale, U955 Équipe 07, Créteil, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Giton
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1085 Institut de Recherche en Santé Environnement et Travail, Institut Fédératif de Recherche 140, Université de Rennes 1, Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U955 Équipe 07, Créteil, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Fiet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1085 Institut de Recherche en Santé Environnement et Travail, Institut Fédératif de Recherche 140, Université de Rennes 1, Rennes, France ; Ecole des Hautes Études en Santé Publique, Rennes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1085 Institut de Recherche en Santé Environnement et Travail, Institut Fédératif de Recherche 140, Université de Rennes 1, Rennes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Mazaud-Guittot
mesh_terms: D000818:Animals; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D004970:Estrone / Q000097:blood; D005260:Female; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004970:Estrone; D004958:Estradiol