Toxic effect of tetra-chlorinated dioxin on ovarian and adrenal cells of BALB/c female mice by studying the expression of CYP11A1 gene

Abstract

Dioxins are a group of environmentally widespread organic pollutants that have a detrimental effect on many organisms. The most important of the group is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Which is the highest toxic of dioxins with a Toxic Equivalent Factor (TEF) of 1.0, Therefore, TCDD could be able to affect the fertility of female mammals by causing changes to the delicate hormonal balance required for ovulation, which affects the reproductive health of women.

Thus, it is of importance to detect the ability of TCDD to change the expression of many genes responsible for transporting and metabolizing cholesterol necessary for the synthesis of sex hormones. P450scc (CYP11A1) enzyme plays a major role in converting cholesterol into the pregnenolone hormone in ovarian Theca cells and adrenal cortex.

This study aimed to investigate the toxic effect of TCDD on ovarian and adrenal cells, by exploring the dose-dependent effects of TCDD, through the relative change in the expression of CYP11A1 gene encoding P450scc enzyme within the mentioned organs, using quantitative polymerase chain reaction technology in Real time RT-qPCR.

The results showed that there were differences in the gene expression of the studied samples, according to the difference in the type of organ and the amount of the given dose We found a decrease in CYP11A1 expression in ovary of all treated groups in comparison with control group.

Where the decrease was higher for the dose 25 μg/kg in comparison with 50 μg/kg. In contrast, for the adrenal gland, our results showed an increase in CYP11A1 expression in all the treated groups in comparison with control group, where the decrease was higher for the dose 50 μg/kg in comparison with 25 μg/kg.

The results of our study concluded that TCDD has the ability to alter the gene expression of CYP11A1 gene in the ovaries and adrenal glands in a dose-dependent manner, and thus the possibility of changing the level of steroidal enzymes, and its impact on the synthesis of steroid hormones, which could eventually lead to disturbances in fertility in female mice.