Hypoglycosylated FSH enhances oocyte quality via increased cell-to-cell interaction during mouse follicle development.

Macroheterogeneity in follicle-stimulating hormone (FSH) β-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is the abundant and more bioactive form in pituitaries of young women, whereas fully glycosylated FSH24 is less bioactive and increases with age. To investigate if the shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, the direct effects of FSH glycoforms on folliculogenesis and oocyte quality were determined using an encapsulated in vitro follicle growth system. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion, and oocyte quality compared to FSH24 (10 ng/ml) treatment. FSH21 enhanced establishment of transzonal projections, gap junctions, and cell-to-cell communication within 24 hrs in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. Our data indicate that FSH21 promotes folliculogenesis and oocyte quality in vitro through increasing cell-to-cell communication early in folliculogenesis and that the shift in in vivo abundance of low FSH21 to high FSH24 with reproductive aging may contribute to the age-dependent decline in oocyte quality.