Premature ovarian failure (POF) is observed in women under 40 years with primary or secondary amenorrhea. The causes for POF are idiopathic, genetic, iatrogenic incidence, autoimmunity, and adverse effects from toxic chemical exposures. Several classes of chemicals have been shown to alter follicle development and reduce fertility, leading to POF in mammals. We investigated the synergistic effects of 4-vinylcyclohexene diepoxide (VCD) and phthalates, including di(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), and di-n-butyl phthalate (DBP), on POF. Both VCD and these phthalates have been reported to disrupt the folliculogenesis and steroidogenesis in many species. In the vehicle group, female Sprague-Dawley rats (8 weeks of age) received an IP injection of corn oil daily for 2 weeks. The 7 other groups received VCD+corn oil, DEHP, DEHP+VCD, BBP, BBP+VCD, DBP, or DBP+VCD. After receiving the VCD or vehicle injection IP for 2 weeks, corn oil or a phthalate were orally administered once a day for the entire 6-week study period. The mRNA expressions of Amh and Sohlh2 were significantly decreased in the combination groups compared to the control and individual groups. Serum Amh levels were significantly lower in the combination groups. Additionally, serum levels of FSH were markedly higher in combination groups. Our findings suggest that the combination of VCD and phthalates can accelerate the POF by disturbance in folliculogenesis and hormone regulation.
NTP Technical Report on the Toxicology and Carcinogenesis Studies of Di-n-butyl Phthalate (CASRN 84-74-2) Administered in Feed to Sprague Dawley (Hsd:Sprague Dawley® SD®) Rats and B6C3F1/N Mice
