title: Endogenous acetaldehyde toxicity during antral follicular development in the mouse ovary.
abstract: The biosynthesis of androgens requires multiple steps and during the conversion of pregnenolone to 17α-hydroxypregnenolone and dehydroepiandrosterone (DHEA) by CYP17a1. Acetaldehyde is potentially formed as a by-product in theca cells during antral follicular development. In this study, acetaldehyde level was significantly increased after eCG stimulation and reached a maximum level at 36-h post-eCG. By 48 h, the level of acetaldehyde decreased in association with the induction of aldehyde dehydrogenase (ALDH) type 1 family members. When immature mice were co-injected with the ALDH inhibitor, cyanamide, and eCG, the expression of genes involved in the differentiations of granulosa cells was suppressed and the number of ovulated oocytes was reduced. The in vitro studies showed that ALDH inhibitors prevented FSH-induced granulosa cell differentiation. These results indicate that acetaldehyde is generated as a by-product during steroidogenesis and can exert toxic effects to impair the differentiation of granulosa cells, reduce ovulation and decrease oocyte quality.
authors.affiliation: Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kawai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mihara
authors.forename: Ikko
authors.initials: I
authors.lastname: Kawashima
authors.forename: Youko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ikeda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Negishi
authors.forename: JoAnne S
authors.initials: JS
authors.lastname: Richards
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003484:Cyanamide / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D003484:Cyanamide; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram