Thyroid hormones, Sertoli cell proliferation and differentiation in progenies from carbamazepine‐treated rat dams during pregnancy and lactation

Abstract

Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg−1 day−1) or vehicle by intra‐peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93‐days post‐partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti‐Ki67, anti‐PCNA, anti‐p27kip1 and anti‐transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27kip1‐positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin‐positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

“…In our experimental studies, it was shown that induced hypothyroidism in female rats caused a decrease in the absolute volume of the endometrium and a reduction in its muscle layer, and in women, hypothyroidism could result in menstrual irregularities and ovulation [1,13]. In men, thyroid hormones also affect the functioning of the gonadal axis, in particular T3, regulate the proliferation and differentiation of Sertoli cells, induce differentiation of Leydig cells, and stimulate steroidogenesis that has been demonstrated in some experimental and clinical studies [14,15].…”