Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subuni...Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.展开更多
基金supported by the National Natural Science Foundation,China(32230108 to Z.Y.)National Key Research and Development Program,China(2022YFF1000300 to Z.Y.and 2022YFD2401800 to G.Z.)Foundation of Hubei Hongshan Laboratory(2021hszd021 to Z.Y.and 2021hskf013 to G.Z.)。
文摘Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.
