Thyroid Hormones Deficiency Impairs Male Germ Cell Development: A Cross Talk Between Hypothalamic-Pituitary-Thyroid, and—Gonadal Axes in Zebrafish

Abstract

In vertebrates, thyroid hormones are critical players in controlling different physiological processes such as development, growth, metabolism among others. There is evidence in mammals that thyroid hormones are also an important component of the hormonal system that controls reproduction, although studies in fish remain poorly investigated. Here, we tested this hypothesis by investigating the effects of methimazole-induced hypothyroidism on the testicular function in adult zebrafish. Treatment of fish with methimazole, in vivo, significantly altered zebrafish spermatogenesis by inhibiting cell differentiation and meiosis, as well as decreasing the relative number of spermatozoa. The observed impairment of spermatogenesis by methimazole was correlated with significant changes in transcript levels for several genes implicated in the control of reproduction. Using an in vitro approach, we also demonstrated that in addition to affecting the components of the brain-pituitary-peripheral axis, T3 (triiodothyronine) also exerts direct action on the testis. These results reinforce the hypothesis that thyroid hormones are an essential element of multifactorial control of reproduction and testicular function in zebrafish and possibly other vertebrate species.

Thyroid axis participates in heat temperature-induced male sex reversal through its activation by the stress response

“…The thyroid and stress axes have been extensively studied individually in relation to testis function (reviewed in [3,12,30,[33][34][35]; however, the interaction between them, particularly on gonadal sex fate,…”

“…THs can affect gonadal development and function in vertebrates [33,[35][36][37][38][39]. Several studies have shown that hypothyroidism decreases plasma androgen levels in sh [35,40,41], birds [42,43], and mammals [37,44,45].…”

“…THs can affect gonadal development and function in vertebrates [33,[35][36][37][38][39]. Several studies have shown that hypothyroidism decreases plasma androgen levels in sh [35,40,41], birds [42,43], and mammals [37,44,45]. Furthermore, during early gonadal development in zebra sh, the exposure to perchlorate, an inhibitor of thyroid hormone synthesis, induced a concentration-dependent bias in the sex ratio toward females, and co-treatment with T4 not only blocked the feminizing effect of perchlorate but also biased the sex ratio toward males [46].…”