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RNA-seq of laser-captured dissected endometrium of WT and Thra1 PV/+ mice

ABSTRACT: RNA-seq of laser-captured dissected endometrium of WT and Thra1 PV/+ mice

PROVIDER: PRJNA1136058 | ENA |

REPOSITORIES: ENA

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RNA-seq of laser-captured dissected endometrium of WT and Thra1 PV/+ mice

Project description:Thyroid hormone receptors (TRs) mediate the genomic actions of the thyroid hormone (T3). Mutations of THRA gene cause a human disease known as resistance to thyroid hormone (RTHa). We created a mouse model expressing a dominant negative mutated TRa1 (Thra1PV/+ mice) that exhibits severely retarded growth, bone abnormalities, constipation, and anemia, as found in RTHa patients. It has been previously observed that female Thra1PV/+ mice exhibit fertility deficiency. In the present study, we aim to understand the molecular basis underlying female infertility caused by TRa1 mutants. The uterus of mutant mice atrophied with 50-60% reduction in weight, as compared with wild-type (WT) mice with reduced proliferation, increased apoptosis, and loss of ~90% of uterine glands. Fibrosis of the endometrium and squamous metaplasia were detected in the uterine epithelium of all Thra1PV/+ mice examined. RNA-seq analysis of laser-captured micro-dissected endometrium to understand the gene expression changes that lead to uterine atrophy, epithelium metaplasia, immune cells infiltration and ectopic expression of IL-33.Analysis of altered gene expression profiles has reveled by RNA-seq analysis provide new insights to understand how thyroid dysfunction could lead to female infertility.

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