Z-cells and oogonia/oocytes in the advanced process of autophagy are the dominant altered cells in the ovaries of hypothyroid newborn rats

Induced prenatal hypothyroidism in rat pups leads to accelerated primordial follicle assembly and premature follicular atresia with ovary failure. This work investigates the influence of maternal hypothyroidism induced with 6-n-propyl-2-thyouracil (PTU) on the number and morphology of oogonia/oocytes in newborn rat pups with light and transmission electron microscopy. Expression of apoptosis and autophagy markers in oogonia/oocytes were examined using immunohistochemistry. Hypothyroid newborn pups had a decreased number of mitotic and resting oogonia, while the number of altered oogonia/oocytes was increased. Ultrastructural observations revealed the increased presence of degenerated pachytene oocytes (Z-cells) and oogonia/oocytes undergoing autophagy, apoptosis and combined apoptosis and autophagy, in this group. The most abundant altered oogonia/oocytes in the hypothyroid group were those with morphological features of advanced autophagy and Z-cells. The percentage of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) positive oogonia/oocytes was significantly lower in the hypothyroid group. No significant difference was recorded in the expression of caspase-3, ATG7 and LC3 possibly reflecting that these proteins were not involved in the oogonia/oocyte alteration process during prenatal rat hypothyroidism. The obtained results indicate that developmental hypothyroidism in the offspring enhances the number of Z-cells and oogonia/oocytes altered with the advanced process of autophagy.