Grosbois Johanne, Srsen Vlastimil, Muñoz Grande Alba, Picton Helen M, Telfer Evelyn E
Reproduction. 2025 May 22;169(6). doi: 10.1530/REP-25-0010. Print 2025 Jun 1.
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.
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.
尽管绵羊已被广泛用作人类卵巢生物学的大型动物模型，但与女性不同的是，它们的繁殖活动具有明显的季节性，其卵巢变化的潜在机制和程度在很大程度上仍不明确。本研究揭示了整个繁殖季节卵巢细胞外基质的动态重塑，这可能是导致观察到的卵巢形态学和卵泡动态变化的另一个驱动因素。
卵巢功能需要其细胞外基质（ECM）提供动态的组织重塑。在季节性繁殖动物中，卵巢经历额外的年度周期性复苏和退化。虽然越来越多的证据表明ECM影响正常的卵巢周期性和功能，但在大型哺乳动物中尚未探讨其成分在整个繁殖季节是如何重塑的。我们通过免疫组织学和体外实验，研究了繁殖季节对卵巢形态学、ECM特性和体外卵泡发育潜能的影响。发情间期卵巢重量和体积减小（P < 0.001）。卵泡密度、窦前卵泡比例及更早发育阶段均不受季节影响，但发情间期窦状卵泡百分比增加（P = 0.028），而黄体仅存在于繁殖季节采集的卵巢中。与此同时，卵巢ECM组成发生显著重塑，与繁殖季节相比，发情间期基质胶原蛋白和纤连蛋白显著增加（P < 0.01），层粘连蛋白减少（P = 0.032）。这与发情间期基质和白膜中更粗的胶原纤维相关。在体外，从其天然环境中分离的窦前卵泡表现出依赖季节的卵泡完整性、存活、窦腔形成和生长模式。这些结果表明在发情间期建立了更硬的卵巢微环境，其与内分泌变化一起调节卵泡生长、退化和排卵反应。
