Investigating the Differential Effects of FSH Glycoforms on FSH Receptor oligomerisation in granulosa cells: Implications for Age-Dependent Fertility Modulation

Abstract

This study explores the differential effects of FSH glycoforms, FSH21 and FSH24, on FSH receptor (FSHR) oligomerisation in mouse granulosa cells across different age groups. Utilizing PD-PALM imaging, we observed age-related variations in FSHR oligomerisation. In younger mice (8 weeks), FSH21 induced a rapid increase in FSHR association at 2 minutes, but this effect was not sustained at later time points. In middle-aged mice (12 months), FSH21 showed a notable but inconsistent enhancement of FSHR oligomerisation, particularly in forming larger oligomeric complexes, whereas FSH24 had a more subtle effect. In older mice (18 months), responses to FSH21 were variable and less consistent, indicating age-dependent changes in FSHR behaviour. The study suggests that hypo-glycosylated FSH21 may be more bioactive in younger and middle-aged individuals, potentially offering advantages in ART protocols requiring rapid follicular stimulation. However, the effects of FSH24, while less pronounced, could be more suited for sustained receptor activation. These findings emphasize the need for age-specific considerations in fertility treatments and contribute to a better understanding of how FSH glycoforms influence FSHR dynamics throughout the reproductive lifespan.