Follicle-stimulating hormone (FSH) is essential for ovarian follicle development and undergoes different age-specific N-glycosylation, leading to distinct FSH glycoforms. Hypoglycosylated FSH21 is abundant in younger women while fully glycosylated FSH24 is more abundant in post-menopausal women. Here, Aubrey Converse, Rajendra Kumar, Francesca Duncan and colleagues investigate how different FSH glycoforms affect follicle development and oocyte quality in mice. First, using an ex vivo mouse follicle growth system, the authors culture follicles with either FSH21 or FSH24 and observe that FSH21 can enhance follicle growth and improve oocyte quality compared with FSH24. Then, to understand the mechanisms behind the positive effects of FSH21 on oocyte development, the authors focus on the cell-cell interactions within follicles. They find that FSH21 enhances the establishment of cell communication within follicles through a gap junction-mediated mechanism, which in turn stimulates follicle growth and improves oocyte quality. Furthermore, the authors treat the cultured follicles with FSH21 together with a gap junction inhibitor and find that the positive effect of FSH21 on follicle growth is removed. Overall, the findings suggest that the decline in oocyte quality with reproductive age might be due to a shift in the abundance of different FSH glycoforms.
