Disruption of Thyroid Hormone Receptor Thrab Leads to Female Infertility in Zebrafish

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Thyroid hormones (THs) T4 and T3 are vital for development, growth, and metabolism. Thyroid dysfunction can also cause problems in fertility, suggesting involvement of THs in reproduction. In zebrafish, there exist 2 forms of TH receptor alpha gene (thraa and thrab). Disruption of these genes by CRISPR/Cas9 showed no reproductive irregularities in the thraa mutant; however, inactivation of the thrab gene resulted in female infertility. Although young female mutants (thrabm/m) showed normal ovarian development and folliculogenesis before sexual maturation, they failed to release eggs during oviposition after sexual maturation. This spawning failure was due to oviductal blockage at the genital papilla. The obstruction of the oviduct subsequently caused an accumulation of the eggs in the ovary, resulting in severe ovarian hypertrophy, abdominal distention, and disruption of folliculogenesis. Gene expression analysis showed expression of both TH receptors and estrogen receptors in the genital papilla, suggesting a direct TH action and potential interactions between thyroid and estrogen signaling pathways in controlling genital papilla development and function. In addition to their actions in the reproductive tracts, THs may also have direct effects in the ovary, as suggested by follicle atresia and cessation of folliculogenesis in the heterozygous mutant (thrab+/m), which was normal in all aspects of female reproduction in young and sexually mature fish but exhibited premature ovarian failure in aged females. In summary, this study provides substantial evidence for roles of THs in controlling the development and functions of both reproductive tract and ovary.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:165

Enthalten in:

Endocrinology - 165(2024), 5 vom: 29. März

Sprache:

Englisch

Beteiligte Personen:

Ai, Nana [VerfasserIn]
Han, Cho Rong [VerfasserIn]
Zhao, Hui [VerfasserIn]
Cheng, Sheue-Yann [VerfasserIn]
Ge, Wei [VerfasserIn]

Links:

Volltext

Themen:

Estrogen
Folliculogenesis
Journal Article
Oviduct
Research Support, Non-U.S. Gov't
Thyroid Hormone Receptors alpha
Thyroid hormone receptor
Zebrafish
Zebrafish Proteins

Anmerkungen:

Date Completed 25.04.2024

Date Revised 26.04.2024

published: Print

Citation Status MEDLINE

doi:

10.1210/endocr/bqae037

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370174070