Characterization of Sexual Trait Development in cyp17a1-Deficient Zebrafish

Abstract

Cytochrome P450 (Cyp)17A1 has both 17α-hydroxylase and 17,20-lyase activities, which are involved in the steroidogenic pathway that produces androgens and estrogens. Previously, a phenotype of all-male cyp17a1-deficient zebrafish generated by transcription activatorlike effector nuclease has been reported. In the current study, the mechanisms relating to Cyp17a1 that are involved in the development of sexual traits, especially gonadal differentiation and testicular development, were characterized. We found that the cyp17a1-deficient fish at 3 months postfertilization (mpf) were all fertile males with normal testis and spermatogenesis but compromised male-typical mating behaviors and secondary sex characters (SSCs), including breeding tubercles, body pigmentation, and anal fin coloration. These results demonstrate that spermatogenesis and testicular development are not as susceptible to androgen deficiency compared with the formation of male-typical SSCs and mating behaviors in zebrafish. The differentiation of the juvenile ovary into the mature ovary failed during the critical sexual differentiation stage. This all-male phenotype of the cyp17a1-deficient fish could be restored with testosterone or estradiol treatment. For testicular development in cyp17a1-deficient fish, a gradually increasing number of spermatozoa and testis hypertrophy from 3 to 6 mpf were observed, accompanied by constitutively upregulated pituitary gonadotropin FSH subunit β (fshβ). The hypertrophic testis and enhanced spermatogenesis in the cyp17a1-deficient fish at 6 mpf could be effectively rescued by fshβ depletion. These results confirm that adequate estrogen is essential for maintaining ovarian differentiation, and they provide new insight into the role of FSHβ in male testicular development and spermatogenesis.

Integration of ATAC-seq and RNA-seq Unravels Chromatin Accessibility during Sex Reversal in Orange-Spotted Grouper (Epinephelus coioides)

“…However, unlike other genes, cyp17a1 exhibited an entirely different expression pattern in ovary and testis and its distribution varied in different germ cells [41]. The condition of cyp17a1 hinted at the distinct roles in female and male which is agreed with the results in zebrafish [42]. These data will provide useful guideposts to distinguish different cell types; however, the specific functions of these sex-related genes in gonadal development requires further study.…”

Transcriptome profiling of laser-captured germ cells and functional characterization of zbtb40 during 17alpha-methyltestosterone-induced spermatogenesis in orange-spotted grouper (Epinephelus coioides)

“…In Cyp17deficient mice, the male are infertile, and the androgen levels dropped significantly [40]. Similarly, in cyp17a1-deficient zebrafish, the androgen levels declined significantly, and their male-typical mating behaviors and secondary sex characters were compromised [41,42]. The colocalization analysis indicated that zbtb40 and cyp17a1 may have interaction during the spermatogenesis in the orange-spotted grouper.…”

Gonadal Transcriptome Analysis of Sex-Related Genes in the Protandrous Yellowfin Seabream (Acanthopagrus latus)

“…The sexual dimorphism of cyp17a has been observed in several fish species (Chen et al, 2010;Xiong et al, 2015). In zebrafish, cyp17a1 mutants develop to all fertile males due to the decreased level of estrogen, demonstrating that cyp17a1 is essential for estrogen production and ovarian maintenance (Zhai et al, 2018).…”