Initiation of delayed ovotoxicity by in vitro and in vivo exposures of rat ovaries to 4-vinylcyclohexene diepoxide.
Repeated daily dosing of rats with the ovotoxic, occupational chemical 4-vinylcyclohexene diepoxide (VCD, 80 mg/kg, i.p.) selectively depletes primordial and primary ovarian follicles. This study was designed to investigate whether follicle loss can be achieved following a single, acute exposure to VCD. Ovaries removed from postnatal-day-4 female Fischer 344 rats were cultured in the absence or presence of VCD for 15 days. Continuous in vitro exposure to VCD (15 days) caused concentration-dependent loss of primordial and small primary follicles. A single exposure to VCD in vitro (30 microM, 24 h) also caused significant losses of primordial and primary follicles 14 days later. Additionally, 28-day-old female rats were given a single injection of VCD (40-320 mg/kg, i.p.). A single dose at 320 mg/kg resulted in substantial loss of all follicle stages beginning 6 days later. Overall, these results demonstrate that an acute exposure to high concentrations/doses of VCD is sufficient to cause subsequent delayed loss of follicles.
Devine
Patrick J
PJ
Department of Physiology, The University of Arizona, 1501 N. Campbell Ave., P.O. Box 245051, Tucson, AZ 85724-5051, USA.
Sipes
I Glenn
IG
Hoyer
Patricia B
PB
D000818:Animals; D017209:Apoptosis; D003510:Cyclohexanes / Q000008:administration & dosage / Q000633:toxicity*; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D009924:Organ Culture Techniques / Q000379:methods; D006080:Ovarian Follicle / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000633:toxicity*
D003510:Cyclohexanes; D053138:Cyclohexenes; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide