TRα1 mutant suppresses KLF9 to cause endometrial metaplasia with ectopic IL-33 expression leading to uterine fibrosis and infertility.

ABSTRACT: Thyroid hormone receptors (TRs) mediate the genomic actions of thyroid hormone. Mutations of THRA gene cause a human disease known as resistance to thyroid hormone (RTHα). We created a mouse model expressing a dominant negative mutated TRα1 (Thra1^PV/+ mice) that exhibits growth retardation, bone abnormalities, constipation, and anemia, as found in RTHα patients. In addition, female Thra1^PV/+ mice exhibit decreased fertility. In the present study, we aimed to characterize the molecular events leading to infertility. Histologically, there was progressive uterine atrophy in Thra1^PV/+ mutant mice, characterized by squamous metaplasia of the endometrial mucosa and endometrial fibrosis. RNA-seq analysis of laser-captured micro-dissected endometrium and spatial tr

SUBMITTER: Edmondson E 

PROVIDER: S-EPMC11785771 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature