Follicle stimulating hormone (FSH) is vital for ovarian function and serum FSH increases with age as ovarian function declines towards menopause. We hypothesize that elevated FSH may rescue follicles from a diminishing pool normally excluded from selection and thereby reducing oocyte function. Transgenic FSH (TgFSH) mice expressing progressively rising FSH levels with age displayed increased litter size initially but after 6 months of age caused decreased littersize and premature infertility due to increased embryo-fetal resorption; however, the specific mechanism was undefined. We hypothesized that increased circulating FSH exceeding a threshold impaired oocyte development and functionality.
We examined oocyte in vitro maturation and aneuploidy (CREST immunofluorescent staining) and cumulus cells (from cumulus-oocyte complexes) for gene expression analysis (qPCR) in TgFSH and non-TgFSH control mice aged 6, 12, 18 and 24 months. Oocytes of TgFSH mice exhibited increased accumulation in the GV stage (20%, p < 0.05) accompanied by reduction in MII stage of maturation (10%, p < 0.05) vs age-matched littermate controls. The reduced oocyte progression to the MII stage is attributable to stalling of the oocytes in the GC stage. The proportion of aneuploid oocytes increased with age (p < 0.001) but did not differ between genotypes (p = 0.83).
We conclude that high FSH has detrimental effects on oocyte maturation/development but does not increase the aneuploidy rate. This suggests that the previously observed age-related subfertility of TgFSH female mice older than 6 months of age is not due to aneuploidy but could be due to other aspects of oocyte health/functionality and warrants further investigation.