Endocrine Abstracts

Ovarian ageing is a naturally occurring physiological process, marked by dynamic changes in ovarian function and hormone secretion. A key of ovarian regulator is follicle stimulating hormone (FSH). FSH is secreted as two glycosylation variants: partially glycosylated FSH (FSH21) and fully glycosylated FSH (FSH24). Analysis has shown that the ratio of FSH21:FSH24 changes with age, with FSH21 predominant during reproductive prime, and FSH24 predominant around menopause. How FSH glycoforms modulate follicle function in the ageing ovary remains unknown. This study aimed to determine the effects of FSH21 and FSH24 on follicle growth and survival in young versus ageing mice. Mouse ovarian follicles were isolated from 12-16wk-old (reproductive prime), 6-8-month (ageing) and 11+ month old (approaching ovaria senescence) C57/BL6 mice and treated -/+10ng/ml, FSH21, FSH24. Mimicking changes in ratios of FSH21:FSH24 that occur with ageing, follicles were additionally treated with 80:20 FSH21:FSH24 (mimic reproductive prime), or 20:80 FSH21:FSH24 (mimic menopause). Follicles were cultured for up to 96hrs and imaged daily to evaluate follicle morphology, with follicles snap frozen at 24hr intervals, for RNA sequencing. Morphological assessment revealed that age impacted follicle response to FSH glycoforms, with FSH21 and 80:20 FSH21:FSH24 increasing follicle growth across all time points in 12-16wk, while 80:20 FSH21:FSH24 increased 6month follicle growth, from 48-to96hrs. 20:80 FSH21:FSH24 increased 11+month follicle growth from 48hrs. Treatment of follicles with FSH24 or 20:80 FSH21:FSH24 resulted in decreased survival rates in the 12-week follicles, whereas 80:20 FSH21:FSH24 decreased survival rates in 11+month follicles. RNASeq analysis revealed both FSH glycoform and age-dependent differences in gene expression in size-matched pre-antral follicles isolated from 12-week and 11+month mice. These data suggest that FSH glycosylation distinctly modulate the follicular microenvironment to control follicle growth and survival, in an age-specific manner.