The relationship of 4-vinylcyclohexene diepoxide toxicity with cell death, oxidative stress, and gap junctions in female rat ovaries

Purpose: It was aimed to investigate the damage caused by VCD toxicity in the ovary, which women working in the industrial field are frequently exposed to, and to show the relationship between gap junction protein, oxidative stress, and apoptosis, which is thought to be effective in the emergence of this damage. Methods: Rats were divided into three groups as control, sham, and VCD. Histological stainings were performed for histopathological evaluations in ovary. Serum AMH level was measured with the ELISA. Then, iNOS, caspase 3, connexin 43 protein, and mRNA expression levels were analyzed by immunohistochemistry and RT-qPCR methods. Results: As a result of the analyses, different amounts of degenerations such as hemorrhage, vacuolization, and fibrosis were observed in the ovary. VCD group AMH level decreased compared to control. In VCD group, iNOS and caspase 3 expressions increased, while connexin 43 expression decreased. Conclusions: It was shown that VCD caused damage to all ovarian tissue. Also, it was revealed for the first time that VCD triggered apoptosis by increasing oxidative stress in the ovary and suppressed connexin 43 which was also effective in the survival of granulosa cells. The devastating effect of exposure to occupational chemicals such as VCD on fertility was demonstrated in this study.