Transdifferentiation of differentiated ovary into functional testis by long-term treatment of aromatase inhibitor in Nile tilapia.
Females with differentiated ovary of a gonochoristic fish, Nile tilapia, were masculinized by long-term treatment with an aromatase inhibitor (Fadrozole) in the present study. The reversed gonads developed into functional testes with fertile sperm. The longer the fish experienced sex differentiation, the longer treatment time was needed for successful sex reversal. Furthermore, Fadrozole-induced sex reversal, designated as secondary sex reversal (SSR), was successfully rescued by supplement of exogenous 17β-estradiol. Gonadal histology, immunohistochemistry, transcriptome, and serum steroid level were analyzed during SSR. The results indicated that spermatogonia were transformed from oogonia or germline stem cell-like cells distributed in germinal epithelium, whereas Leydig and Sertoli cells probably came from the interstitial cells and granulosa cells of the ovarian tissue, respectively. The transdifferentiation of somatic cells, as indicated by the appearance of doublesex- and Mab-3-related transcription factor 1 (pre-Sertoli cells) and cytochrome P450, family 11, subfamily B, polypeptide 2 (pre-Leydig cells)-positive cells in the ovary, provided microniche for the transdifferentiation of germ cells. Decrease of serum 17β-estradiol was detected earlier than increase of serum 11-ketotestosterone, indicating that decrease of estrogen was the cause, whereas increase of androgen was the consequence of SSR. The sex-reversed gonad displayed more similarity in morphology and histology with a testis, whereas the global gene expression profiles remained closer to the female control. Detailed analysis indicated that transdifferentiation was driven by suppression of female pathway genes and activation of male pathway genes. In short, SSR provides a good model for study of sex reversal in teleosts and for understanding of sex determination and differentiation in nonmammalian vertebrates.
Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education) (L.-N.S., X.-L.J., Q.-P.X., J.Y., B.-F.H., W.-J.T., L.-Y.Z., D.-S.W.), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715 Chongqing, People's Republic of China; Solution-Oriented Research for Science and Technology (Y.N.) and Laboratory of Reproductive Biology (Y.N.), National Institute for Basic Biology, Okazaki 444-8585, Japan; and South Ehime Fisheries Research Center (Y.N.), Ehime University, Matsuyama 790-8577, Japan.
Li-Na
LN
Sun
Xiao-Long
XL
Jiang
Qing-Ping
QP
Xie
Jing
J
Yuan
Bao-Feng
BF
Huang
Wen-Jing
WJ
Tao
Lin-Yan
LY
Zhou
Yoshitaka
Y
Nagahama
De-Shou
DS
Wang
D000818:Animals; D047072:Aromatase Inhibitors / Q000737:chemistry*; D054338:Cell Transdifferentiation / Q000187:drug effects*; D023681:Cichlids; D004958:Estradiol / Q000737:chemistry; D017316:Fadrozole / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D010053:Ovary / Q000187:drug effects* / Q000502:physiology*; D013737:Testis / Q000187:drug effects* / Q000502:physiology*; D013739:Testosterone / Q000031:analogs & derivatives / Q000737:chemistry; D013997:Time Factors
D047072:Aromatase Inhibitors; D013739:Testosterone; D004958:Estradiol; D017316:Fadrozole; C003600:11-ketotestosterone