Effect of bcl-2 overexpression in mice on ovotoxicity caused by 4-vinylcyclohexene.
The occupational chemical 4-vinylcyclohexene (VCH) destroys small preantral ovarian follicles in mice following repeated daily dosing. The cell survival gene bcl-2 is thought to protect against follicular death during embryogenesis because primordial follicle numbers in newborn bcl-2 overexpressing (OE) mice are greater than in wild-type (WT) controls. Thus, this study was designed to determine if overexpression of bcl-2 protects against VCH-induced follicle loss during embryonic development. Pregnant bcl-2 OE or WT mice were dosed (p.o.) daily with VCH (500 mg/kg) or sesame oil (vehicle control) on days 8-18 of pregnancy. Ovaries were collected from moms and female pups on pup postnatal day (PND) 8. Nonpregnant OE and WT females were also treated with VCH (500 mg/kg p.o.) or vehicle and evaluated in the same manner. As previously reported, ovaries from PND8 OE female pups contained 50% more primordial follicles than WT pups (P < 0.05). Unlike WT pups, relative to vehicle controls, in utero exposure to VCH resulted in a reduction in primordial (25% of control), primary (38% of control), and secondary (33% of control) follicles in ovaries of OE pups (P < 0.05). VCH had no significant effect on follicle numbers in OE or WT moms. Conversely, in nonpregnant adults, VCH did not affect WT mice but caused loss of primordial (55% of control), primary (51% of control), and secondary (69% of control) follicles in OE mice (P < 0.05). These results demonstrate that bcl-2 overexpression does not protect against, but instead increases susceptibility to VCH-induced follicle loss in transplacentally exposed or in nonpregnant mice.
Flaws
Jodi A
JA
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Marion
Samuel L
SL
Miller
Kimberly P
KP
Christian
Patricia J
PJ
Babus
Janice K
JK
Hoyer
Patricia B
PB
D000818:Animals; D003510:Cyclohexanes / Q000633:toxicity*; D053138:Cyclohexenes; D005260:Female; D019254:Genes, bcl-2; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects; D010063:Ovum / Q000187:drug effects*; D011247:Pregnancy
D003510:Cyclohexanes; D053138:Cyclohexenes; C013733:4-vinylcyclohexene