title: Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.
abstract: Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.
authors.affiliation: Centre of Reproduction, Development and Aging (Z.Z., W.G.), Faculty of Health Sciences, University of Macau, Taipa, Macau China; and School of Life Sciences (Z.Z., S.-W.L., L.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Centre of Reproduction, Development and Aging (Z.Z., W.G.), Faculty of Health Sciences, University of Macau, Taipa, Macau China; and School of Life Sciences (Z.Z., S.-W.L., L.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Shuk-Wa
authors.initials: SW
authors.lastname: Lau
authors.affiliation: Centre of Reproduction, Development and Aging (Z.Z., W.G.), Faculty of Health Sciences, University of Macau, Taipa, Macau China; and School of Life Sciences (Z.Z., S.-W.L., L.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Centre of Reproduction, Development and Aging (Z.Z., W.G.), Faculty of Health Sciences, University of Macau, Taipa, Macau China; and School of Life Sciences (Z.Z., S.-W.L., L.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D012734:Disorders of Sex Development / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D055786:Gene Knockout Techniques / Q000379:methods; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009154:Mutation; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D013737:Testis / Q000196:embryology / Q000378:metabolism; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011962:Receptors, FSH; D011974:Receptors, LH; D029961:Zebrafish Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone