Exploring the Role of Estrogens in Lizard Spermatogenesis through the Study of Clomiphene and FSH Effects

Abstract

Spermatogenesis is a fascinating biological process aiming to generate haploid spermatozoa from diploid spermatogonia through a specific hormonal network between gonadotropins and steroids. Increasing evidence suggests that the primary female sex hormone estrogen plays an active role in this process. This research points out on the role of estrogen during lizard spermatogenesis by using three experimental approaches: (1) exposure to an analogue of nonsteroidal estrogen as Clomiphene citrate that acts both as estrogen agonist and antagonist; (2) exposure to the gonadotropin FSH; and (3) exposures to FSH followed by Clomiphene. Histological and immunohistochemical results demonstrate that in the lizard Podarcis sicula during the mating period, Clomiphene as well as FSH determines the breakdown of spermatogenesis and the epididymal regression, presumably through estrogens input as indirectly demonstrated by the appearance of ERα and vitellogenin in the liver. The ability of Clomiphene to restore the gonadal natural condition after FSH treatment is also demonstrated. Finally, data indicate that lizard testis and epididymis control their morphophysiology regulating the intracellular presence of ERα.

Role of estrogen receptors, P450 aromatase, PCNA and p53 in high-fat-induced impairment of spermatogenesis in rats

“…The hyperplasia of the interstitial connective tissue is also recorded. These histological damages have been correlated with a high estrogenic activity in other vertebrates with tubular testis organization [29,[44][45][46][47][48][49]. The hyperplasia of testicular connective tissue is well documented in rats and lizards exposed to estrogen or in fish treated with estrogen-like substances [47,50,51].…”

The Italian Wall Lizard Podarcis siculus as a Biological Model for Research in Male Reproductive Toxicology

“…Clomiphene administration to male lizards treated with FSH induces an increase in estrogen and a consequent modification in the testicular morphology. This result demonstrates that clomiphene restored the right estrogen level typical of the reproductive period [ 55 ]. All these data once again emphasize the importance of estrogen, i.e., the main female hormone, for the correct progression of spermatogenesis.…”

“…Clomiphene, a member of the selective estrogen receptor modulator (SERM) family, acts as an estrogen agonist when the hormone is in low concentration and as an antagonist at high estrogen concentrations [ 54 ]. The exposure of lizards to clomiphene during the mating period, when the estrogen level is low, led to the slowdown in spermatogenesis, the thinning of the seminiferous epithelium with degenerate germ cells, and the reduction of the secretive activity of the epididymal corpus; these changes represent the classical alterations due to estrogenic exposure [ 55 ]. Clomiphene administration to male lizards treated with FSH induces an increase in estrogen and a consequent modification in the testicular morphology.…”

Integrated mRNA and miRNA expression profile analyses reveal the potential roles of sex‐biased miRNA–mRNA pairs in gonad tissues of the Chinese concave‐eared torrent frog (Odorrana tormota)

“…Males are more common than females in the wild. The mechanism of the sexually dimorphic Vertebrate seasonal breeders are an excellent model to understand the spermatogenic mechanisms underlying spermatogenesis (Verderame, Scudiero, & Limatola, 2017). Increasing evidence suggests that miRNAs play an important role as regulators of reproduction (Lei, Jin, Gonzalez, Behringer, & Woodruff, 2010;Murchison et al, 2007).…”

“…Vertebrate seasonal breeders are an excellent model to study the spermatogenic mechanisms underlying spermatogenesis (Verderame et al, ). During spermatogenesis, the characteristic morphology of the spermatozoon is acquired through the assembly of cytoskeletal components to form the various necessary structures present in mature spermatozoa, including the perinuclear theca, the acrosome and the flagellum (Yoshinaga & Toshimori, ).…”