Effects of Hypothyroidism on Proliferation and Programmed Cell-Death in Rat Ovarian Granulosa Cells

Abstract

Hypothyroidism is the most common endocrine disease, after diabetes. Thyroid hormones are essential for genital organs function. In this study, we aimed to determine the apoptotic and cell proliferation indexes resulting from reduced thyroid hormones in rat ovarian follicles. For the purpose of this study, 20 female mature Wistar rats were divided into test and control groups. The test group underwent chemical thyroidectomy by receiving 500 mg/l propylthiouracil added to drinking water. The control group only received ordinary drinking water. After three weeks, the rats were sacrificed and their ovaries were removed and fixed for tissue preparation. Triphosphate-biotin nick end-labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemical techniques were applied to determine apoptosis and cell proliferation variations. Our findings revealed that apoptotic index significantly diminished in large antral follicles. There were no significant differences between the two groups in terms of primary and pre-antral follicles. No TUNEL-positive cell was noted in primordial follicles in the both groups. Cell proliferation index revealed a significant decrease in follicular growth of pre-antral to graafian follicles in the hypothyroid group. PCNA-positive cells were not observed in primordial follicles in the both groups. The results of the study suggested that reduced thyroid hormones lead to a wide range of hormonal changes, and factors existing in follicular fluid, especially in large antral follicles, undergo transformations that affect apoptotic and cell proliferation indexes. The process of follicular growth occurs by entrance of follicles to the next growth phase without inducing sufficient potentiality, and the produced ovules might be healthy or morphologically defected.