Steroidogenesis-disrupting compounds can be effectively studied for major fertility-related endpoints using in vitro cultured mouse follicles.
Biologically relevant bioassays are needed to test various endocrine disrupters (EDs). A mouse follicle culture model could allow measuring steroidogenic enzyme function in combination with oocyte growth and meiotic maturation using routine methodology. Three steroidogenesis-disrupting 'model' chemicals were tested; vorozole (VOR), aminoglutethimide (AMG), and ketoconazole (KCZ). Along with visual assessment of follicular growth, differentiation and oocyte growth and maturation by conventional light microscopy, steroid secretion measurements allowed to confirm literature findings from in vivo animal studies and more complex in vitro tests. The bioassay was applied for a dose-response study of mono(2-ethylhexyl)phthalate (MEHP), a chemical known to disrupt several steroidogenic enzymes. This bioassay was able to confirm an increased inactivation of E(2) to E(1) and an induced precocious progesterone increase, implying that MEHP can disrupt follicle differentiation and impact the reproductive axis. This in vitro ovarian model allows to reduce animal use by performing synchronous culture of large numbers of early preantral ovarian mouse follicles and is informative on multiple fertility-related endpoints.
Lenie
Sandy
S
Follicle Biology Laboratory, Vrije Universiteit Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium. Sandy.Lenie@vub.ac.be
Smitz
Johan
J
D000616:Aminoglutethimide / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012680:Sensitivity and Specificity; D013256:Steroids / Q000096:biosynthesis*; D018675:Toxicity Tests / Q000379:methods*; D014230:Triazoles / Q000633:toxicity
D052244:Endocrine Disruptors; D013256:Steroids; D014230:Triazoles; D000616:Aminoglutethimide; C060523:vorozole; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; D007654:Ketoconazole