Depletion of follicles accelerated by combined exposure to phthalates and 4-vinylcyclohexene diepoxide, leading to premature ovarian failure in rats

Humans are at daily risk by simultaneous exposures to a broad spectrum of man-made chemicals in the commercial products. Several classes of chemicals have been shown to alter follicle development and reduce fertility, leading to premature ovarian failure (POF) in mammals. We investigate the synergistic effects of 4-vinylcyclohexene diepoxide (VCD) and phthalate, including di(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) on POF. Combination exposure with VCD and phthalate significantly reduced the numbers of primary follicles. The expressions of Amh and Sohlh2 were significantly decreased in the combination groups. Serum Amh levels were significantly lower in the combination groups. Additionally, serum levels of follicle-stimulating hormone were significantly increased in combination groups. Taken together, exposure to phthalates promotes the depletion of follicular follicles and consequently increases the risk of premature menopause, and combined exposure of phthalates and VCD to early menopausal women is likely to aggravate the POF syndrome.