Reproductive seasonality influences follicle dynamics and the ovarian extracellular matrix structural properties in ewes.

IN BRIEF: Although sheep have been widely used as a large animal model for human ovarian biology, unlike women, they display a marked seasonality of breeding activity, the underlying mechanisms and extent of ovarian changes of which remain largely undefined. This study reveals the active remodeling of the ovarian extracellular matrix across the reproductive season, which could be an additional driver responsible for the observed variations in ovarian morphometry and follicle dynamics. ABSTRACT: Ovarian function requires dynamic tissue remodeling provided by its extracellular matrix (ECM). In seasonal breeders, ovaries undergo an additional circannual cycle of recrudescence and regression. While increasing evidence suggests that the ECM impacts normal ovarian cyclicity and function, how its components are remodeled across reproductive seasonality has not been explored in large mammals. Using immunohistological and in vitro experiments, we investigated the influence of reproductive seasonality on ovarian morphometry, ECM properties and follicle developmental potential in vitro. Ovarian weight and volume were reduced during anestrus (P < 0.001). Neither follicular density nor the proportion of preantral follicles and earlier stages of development were impacted by the season, but the percentage of antral follicles increased during anestrus (P = 0.028), while corpora lutea were only present in ovaries collected during the breeding season. Concomitantly, ovarian ECM composition was significantly remodeled, with stromal collagen and fibronectin significantly increased (P < 0.01) and laminin decreased (P = 0.032) during anestrus compared to the breeding season. This correlated with thicker collagen fibers both in the stroma and in the tunica albuginea during anestrus. In vitro, preantral follicles isolated from their native environment exhibited a season-dependent pattern of follicular integrity, survival, antrum formation and growth. These results suggest the establishment of a stiffer ovarian microenvironment during anestrus, which, together with endocrine changes, regulates follicle growth, demise and the ovulatory response.