Ectopic expression of CGG-repeats alters ovarian response to gonadotropins and leads to infertility in a murine FMR1 premutation model.

ABSTRACT: Women heterozygous for an expansion of CGG repeats in the 5'UTR of FMR1 risk developing fragile X-associated primary ovarian insufficiency (FXPOI) and/or tremor and ataxia syndrome (FXTAS). We show that expanded CGGs, independent of FMR1, are sufficient to drive ovarian insufficiency and that expression of CGG-containing mRNAs alone or in conjunction with a polyglycine-containing peptide translated from these RNAs contribute to dysfunction. Heterozygous females from two mouse lines expressing either CGG RNA-only (RNA-only) or CGG RNA and the polyglycine product FMRpolyG (FMRpolyG+RNA) were used to assess ovarian function in aging animals. The expression of FMRpolyG+RNA led to early cessation of breeding, ovulation and transcriptomic changes affecting cholesterol and steroid hormone biosynt

SUBMITTER: Shelly KE 

PROVIDER: S-EPMC8165648 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature