Abstract
Cortisol is the major endocrine factor mediating the inhibitory effects of stress on vertebrate reproduction. It is well known that cortisol affects reproduction by interacting with the hypothalamic–pituitary–gonads axis, leading to downstream inhibitory and stimulatory effects on gonads. However, the mechanisms are not fully understood. In this study, we provide novel data demonstrating the stimulatory effects of cortisol on spermatogenesis using an ex vivo organ culture system. The results revealed that cortisol treatment did not modulate basal androgen production, but it influenced transcript levels of a selected number of genes involved in the zebrafish testicular function ar (androgen receptor), star (steroidogenic acute regulatory), cyp17a1 (17α-hydroxylase/17,20 lyase/17,20 desmolase), cyp11a2 (cytochrome P450, family 11, subfamily A, polypeptide 2), hsd11b2 (11-beta hydroxysteroid dehydrogenase), cyp2k22 (cytochrome P450, family 2, subfamily K, polypeptide 22), fkbp5 (FKBP prolyl isomerase 5), grα (glucocorticoid receptor alpha), and grβ (glucocorticoid receptor beta) in a short-term culture. We also showed that cortisol stimulates spermatogonial proliferation and differentiation in an androgen independent manner as well as promoting meiosis and spermiogenesis by increasing the number of spermatozoa in the testes. Moreover, we demonstrated that concomitant treatment with RU 486, a potent glucocorticoid receptor (Gr) antagonist, did not affect the cortisol effects on spermatogonial differentiation but blocked the induced effects on meiosis and spermiogenesis. Supporting the Gr-mediated effects, RU 486 nullified the cortisol-induced expression of sycp3l (synaptonemal complex protein 3), a marker for the meiotic prophase that encodes a component of the synaptonemal complex. This is consistent with in silico analysis that found 10 putative GREs (glucocorticoid response elements) upstream of the zebrafish sycp3l. Finally, we also showed that grα mRNA is expressed in Sertoli and Leydig cells, but also in several types of germ cells, including spermatogonia and spermatocytes. Altogether, this evidence indicates that cortisol exerts paracrine roles in the zebrafish testicular function and spermatogenesis, highlighting its effects on spermatogonial differentiation, meiosis, and spermiogenesis.
Highlights
Cortisol is the primary glucocorticoid hormone in teleost fish released in response to a stressor exposure upon the activation of the hypothalamic–pituitary–interrenal (HPI) axis
We demonstrate that grα and grβ were differentially regulated at the highest concentration of cortisol in the zebrafish testes; while grα mRNA levels were increased, grβ was strongly suppressed (~0.04-fold inhibition)
This study demonstrates for the first time the direct actions of cortisol on the zebrafish spermatogenesis
Summary
Cortisol is the primary glucocorticoid hormone in teleost fish released in response to a stressor exposure upon the activation of the hypothalamic–pituitary–interrenal (HPI) axis (for a review see Schreck and Tort [1]; Milla et al [2]; Faught and Vijayan [3]). Glucocorticoids can impact other physiological functions, including reproduction [1,3,5,8] In this regard, it is widely accepted that stress and cortisol may have inhibitory effects on reproduction in vertebrates including teleost fish [3,10,11,12]. Cyprinus carpio, stress (temperature changes) and cortisol treatment resulted in reduced gonadosomatic index (GSI), delayed testicular development, and decreased plasma androgen levels [17,18]. Chronically elevated cortisol levels in common carp affected all parts of the BPG axis by decreasing hypothalamic GnRH level; pituitary fshβ mRNA level and testicular androgen production in vitro [17,18,19]. Higher concentration of cortisol (100 ng/mL) was found to stimulate testicular production of 11-KT in vitro, which suggests that cortisol-induced spermatogonial proliferation might be mediated by androgens in Japanese eel [21]
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