Insights into the role of Fsh signaling in ovarian differentiation of chorionic gonadotropin α ( cgα)-deficient zebrafish.

IF 4 1区 生物学 Q1 ZOOLOGY
Chuang Shi, Yuqing Zhang, Yao Lu, Qiyong Lou, Guohui Shang, Xuyan Peng, Xiangyan Dai, Xia Jin, Jiangyan He, Gang Zhai, Zhan Yin
{"title":"Insights into the role of Fsh signaling in ovarian differentiation of <i>chorionic gonadotropin α</i> ( <i>cgα</i>)-deficient zebrafish.","authors":"Chuang Shi, Yuqing Zhang, Yao Lu, Qiyong Lou, Guohui Shang, Xuyan Peng, Xiangyan Dai, Xia Jin, Jiangyan He, Gang Zhai, Zhan Yin","doi":"10.24272/j.issn.2095-8137.2024.397","DOIUrl":null,"url":null,"abstract":"<p><p>Chorionic gonadotropin α (Cgα) functions as the shared subunit for thyroid-stimulating hormone subunit β (Tshβ), luteinizing hormone subunit β (Lhβ), and follicle-stimulating hormone subunit β (Fshβ). While these β-subunits have been extensively studied using effective gene knockout models in zebrafish, the biological role of Cgα remains elusive. In this study, <i>cgα</i>-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, cgα deficiency 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 <i>cgα</i>-deficient fish and <i>lhβ</i> <sup><i>-</i>/-</sup> ; <i>fshβ</i> <sup>-/-</sup> mutants. Gonadal sex differentiation in <i>cgα</i>-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of <i>fshβ</i> ( <i>cgα</i> <sup>-/-</sup>; <i>fshβ</i> <sup>-/-</sup>), marked by elevated anti-Müllerian hormone ( <i>amh</i>) expression, or following loss of follicle-stimulating hormone receptor ( <i>fshr</i>) ( <i>cgα</i> <sup>-/-</sup>; <i>fshr</i> <sup>-/-</sup>). <i>In vitro</i> 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 <i>cgα</i>-deficient fish recapitulate those of thyrotropin- and gonadotropin-disrupted models, highlighting the essential role of Cgα in thyroid and gonadal function. Importantly, these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish, including Cgα-independent Fshβ activity and the constitutive functionality of Fshr.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":"46 3","pages":"695-708"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zoological Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.24272/j.issn.2095-8137.2024.397","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ZOOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Chorionic gonadotropin α (Cgα) functions as the shared subunit for thyroid-stimulating hormone subunit β (Tshβ), luteinizing hormone subunit β (Lhβ), and follicle-stimulating hormone subunit β (Fshβ). While these β-subunits have been extensively studied using effective gene knockout models in zebrafish, the biological role of Cgα remains 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, cgα deficiency 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 Cgα in thyroid and gonadal function. Importantly, these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish, including Cgα-independent Fshβ activity and the constitutive functionality of Fshr.

Fsh信号在绒毛膜促性腺激素α (cgα)缺乏斑马鱼卵巢分化中的作用。
绒毛膜促性腺激素α (cga α)作为促甲状腺激素β亚基(Tshβ)、促黄体生成素β亚基(Lhβ)和促卵泡激素β亚基(Fshβ)的共享亚基。虽然这些β-亚基已经在斑马鱼中使用有效的基因敲除模型进行了广泛的研究,但cga α的生物学作用仍然难以捉摸。在这项研究中,通过转录激活因子样效应核酸酶(TALENs)产生的cα -缺陷斑马鱼表现出生存能力,但在幼年期表现出明显的发育异常,包括生长迟缓、色素沉着、甲状腺素(T4)水平降低和前鳔膨胀缺陷。在成年鱼中,cga α缺乏会导致性腺发育中断,第二性征(ssc)受损,并严重影响雌鱼和雄鱼的生殖行为。值得注意的是,在缺乏gα-和lhβ -/-的鱼类中,睾丸和卵巢均出现分化;Fshβ -/-突变体。cga α-缺陷斑马鱼的性腺性别分化在fshβ (cga α- /-;fshβ -/-),以抗勒氏激素(amh)表达升高为标志,或随着促卵泡激素受体(fshr) (cgα -/-;fshr - / -)。在中国仓鼠卵巢(CHO)细胞中进行的体外实验显示,转染编码Fshr、Fshβ/Fshr或Cgα/Fshβ/Fshr的构建物后,cAMP反应元件(CRE)启动子活性增加。总的来说,在促甲状腺激素和促性腺激素紊乱模型中观察到的表型概括了促甲状腺激素和促性腺激素紊乱模型,突出了cga α在甲状腺和性腺功能中的重要作用。重要的是,这些发现揭示了Fsh信号在维持斑马鱼卵巢正常分化中的作用,包括不依赖于cg α的Fshβ活性和Fshr的组成功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信