Propylthiouracil-induced hypothyroidism delays apoptosis during the first wave of spermatogenesis

Abstract

Mammalian germ cell apoptosis plays a key role in controlling the correct number of germ cells supported by Sertoli cells during the fi rst wave of spermatogenesis in mammalian puberty. However, little is known about hormonal factors that could infl uence the rate of germ cell apoptosis during puberty or adulthood. In this work we evaluate germ cell apoptosis under hypothyroidism induced by goitrogen propylthiouracil (PTU) during the fi rst wave of spermatogenesis. Neonatally administered PTU promoted a delay in the differentiation of Sertoli cells as evaluated by the expression of clusterin using immunohistochemistry and RT-PCR. Clusterin had different expression levels in control and PTU-treated animals, but under both conditions the highest levels were found in 35-day-old rats. In addition, clusterin displayed a cytoplasmic localization in control testes, but appeared located in the nucleus in PTU-treated animals. The wave of apoptosis (determined by caspase activity and quantifi cation of apoptotic cells) characteristic of the fi rst round of spermatogenesis was delayed by at least 10 days in these animals. The expression levels of proapoptotic genes like BAX or BAD were different between control and PTU-treated rats; although in both groups the highest level was found at the same age (days). Thus our results indicate that the characteristic pubertal apoptotic wave during rat spermatogenesis is delayed in neonatal hypothyroid rats.

Apoptosis, necrosis and autophagy are influenced by metabolic energy sources in cultured rat spermatocytes

“…Interestingly, spermatocyte apoptosis coincides with opening of the Blood-Tesis-Barrier [47], a condition where spermatocytes are exposed to plasma glucose concentrations. Therefore, we propose that glucose could be an in vivo modulator of spermatocyte apoptosis during spermatogenesis [48][49][50].…”

Elastographic and morphological testicular changes in hypothyroidism – an experimental study

“…On the one hand, it may seem that the effect on fertility of methimazole-induced hypothyroidism has little clinical importance because methimazole is usually prescribed in older aged humans and animals. On the other hand, in humans, the disease may even involve deterioration of sexual performance, which significantly lowers the quality of life (24).…”

“…Iatrogenic hypothyroidism, as a major clinical problem especially in people, cats, and other animal species which are treated with methimazole or other antithyroid drugs, influences numerous functions (3, 4, 10, 11, 12, 16). Naturally occurring hypothyroidism, as a systemic disease, leads to pituitary and testicular damage, especially during hypogonadotropic hypogonadism; however, other reasons for these conditions, such as testicular functional changes, have been found (7, 8, 16, 24). Therefore, it probably differs from iatrogenic thyroid gland insufficiency, in that the spectrum of adverse effects of an antithyroid drug depends on the kind of medicine, its dose, exposure time, and the stage of life when treatment was conducted (3, 26).…”

The Relationship Between Extracellular Matrix Proteins and Germ Cell Apoptosis in Balb/C Mouse Testis Following Experimental Hypothyroidism

“…Additionally, a direct correlation has been reported between developmental changes in the BM composition and the delay in the development of germ cell and Sertoli cell maturation in the testis of the hypothyroid rats (19). On the other hand, previous research represents that germ cell apoptosis plays a vital role in controlling sperm production by Sertoli cells during spermatogenesis in puberty or adulthood (25).…”