Conditions and possible mechanisms of VCD-induced ovarian failure.

ABSTRACT

Perimenopause is an important period in women's lives, in which they experience a series of physiological changes. Current animal models of perimenopause fail to adequately replicate this particular stage in female life, while current in vitro models are too simplistic and cannot account for systemic effects. Neither the naturally-ageing animal model, nor the ovariectomised animal model, mimic the natural transitional process that is the menopause. In vivo and in vitro studies have confirmed that the occupational chemical, 4-vinylcyclohexene diepoxide (VCD), can cause selective destruction of the ovarian primordial and primary follicles of rats and mice by accelerating the apoptotic process, which successfully mimics the perimenopausal state in women. However, it is the in vivo VCD-induced rodent perimenopausal models that are currently the most widely used in research, rather than any of the available in vitro models. Studies on the mechanisms involved have found that VCD induces ovotoxicity via interference with the c-kit/kit ligand and apoptotic signalling pathways, among others. Overall, the VCD-induced perimenopausal animal models have provided some insight into female perimenopause, but they are far from ideal models of the human situation.