Aquaporins constitute a group of water channel proteins located in numerous cell types. These are pore-forming transmembrane proteins, which mediate the specific passage of water molecules through membranes. It is well-known that water homeostasis plays a crucial role in different reproductive processes, e.g., oocyte transport, hormonal secretion, completion of successful fertilization, blastocyst formation, pregnancy, and birth. Further, aquaporins are involved in the process of spermatogenesis, and they have been reported to be involved during the storage of spermatozoa. It is noteworthy that aquaporins are relevant for the physiological function of specific parts in the female reproductive system, which will be presented in detail in the first section of this review. Moreover, they are relevant in different pathologies in the female reproductive system. The contribution of aquaporins in selected reproductive disorders and aging will be summarized in the second section of this review, followed by a section dedicated to aquaporin-related proteins. Since the relevance of aquaporins for the male reproductive system has been reviewed several times in the recent past, this review aims to provide an update on the distribution and impact of aquaporins only in the female reproductive system. Therefore, this paper seeks to determine the physiological and patho-physiological relevance of aquaporins on female reproduction, and female reproductive aging.

During oocyte maturation, granulosa cells (GCs) respond to fluctuating hormone levels in the ovary. The study aims to reveal metabolism and activity patterns of isolated and cultured GCs, reflecting in vivo processes. A downregulation of GARNL3 and ARRDC4 across all time points (48 h, 96 h, and 144 h) suggests reduced cell signaling and response to external stimuli, which may be related to the isolation and in vitro culturing of GCs from the complex ovarian microenvironment. The consistent elevation of LOX underscores its role in extracellular matrix (ECM) cross-linking, crucial for oocyte quality, whereas FN1 and ITGB3 highlight cellular adhesion and ECM interaction during adaptation to in vitro conditions. The study further demonstrates that ANKRD1 and SLC1A1 are upregulated over time in vitro, indicating cellular differentiation and metabolic alterations. Furthermore, proteoglycan and MAPK signaling pathways are identified as key players in cell-to-cell and cell-to-ECM interactions. GSEA revealed heightened activity in vasculature development, the TGF-β signaling pathway, cell development, and lipid response. The findings suggest that while GCs in vitro mimic in vivo processes related to ECM remodeling and oocyte development, they also exhibit a tendency towards aging. The research emphasizes that isolated GCs in vitro exhibit time-dependent activity shifts related to cellular differentiation, ECM remodeling, and lipid metabolism, which also have implications for the understanding of reproductive physiology and pathologies.