Intercellular communication in the cumulus–oocyte complex during folliculogenesis: A review

Abstract

During folliculogenesis, the oocyte and surrounding cumulus cells form an ensemble called the cumulus-oocyte complex (COC). Due to their interdependence, research on the COC has been a hot issue in the past few decades. A growing body of literature has revealed that intercellular communication is critical in determining oocyte quality and ovulation. This review provides an update on the current knowledge of COC intercellular communication, morphology, and functions. Transzonal projections (TZPs) and gap junctions are the most described structures of the COC. They provide basic metabolic and nutrient support, and abundant molecules for signaling pathways and regulations. Oocyte-secreted factors (OSFs) such as growth differentiation factor 9 and bone morphogenetic protein 15 have been linked with follicular homeostasis, suggesting that the communications are bidirectional. Using advanced techniques, new evidence has highlighted the existence of other structures that participate in intercellular communication. Extracellular vesicles can carry transcripts and signaling molecules. Microvilli on the oocyte can induce the formation of TZPs and secrete OSFs. Cell membrane fusion between the oocyte and cumulus cells can lead to sharing of cytoplasm, in a way making the COC a true whole. These findings give us new insights into related reproductive diseases like polycystic ovary syndrome and primary ovarian insufficiency and how to improve the outcomes of assisted reproduction.

Melatonin Exerts an Anti‐Panoptoic Role in Spinal Cord Ischemia‐Reperfusion Injured Rats

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Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome

“…GCs make a substantial contribution to the acquisition of oocyte competence. They are connected to and communicate with the oocyte via a variety of routes such as transzonal projections, gap junctions, microvilli, and extracellular vesicles, through which supply the oocyte with essential metabolites, signaling molecules, and functional RNAs, and thereby participate in the survival, maturation, and development of the oocyte 74 . Thus, it is not surprising that the perturbation of GC homeostasis compromises oocyte competence, leading to poor embryo quality and failure in pregnancy.…”

Cumulus expansion is impaired with advanced reproductive age due to loss of matrix integrity and reduced hyaluronan

“…Cumulus cells provide the oocyte with certain amino acids ( l ‐alanine), pyruvate and cholesterol to support its metabolic activity, since oocytes are unable to metabolize the glucose directly, synthesize cholesterol from acetate, or take up cholesterol via receptor‐mediated selective uptake (Su et al, 2009). Follicular fluid, which fills the antral follicle cavity, reflects the metabolism and synthetic capacity of the surrounding granulosa and cumulus cells (Babayev & Duncan, 2022; Rodgers & Irving‐Rodgers, 2010; Xie et al, 2023). With reproductive aging, both the cumulus cells and follicular fluid exhibit significant genomic, epigenetic, transcriptomic, proteomic, and metabolic alterations (Babayev & Duncan, 2022).…”