Figure 5:

The Summarized Pathway of Oocyte-Derived Paracrine Factors Contributing to the Maintenance of Meiotic Arrest in Mammalian Oocytes

This figure presents the key pathways involving oocyte-derived paracrine factors, namely FSH/FHSR, Estrogen/ER, and NPPC/NPR2 that are essential for maintaining meiotic arrest in mammalian oocytes.

Orange Cycle: Within the mural granulosa cells (MGC), the binding of FSH to its receptor (FSHR) collaborates with Estrogen/ER, stimulating the production of NPPC. This, in turn, triggers the arrival of protein kinase A (mainly Cx43) in the cumulus granulosa cells (CGC), facilitating the cooperation between NPPC and NPR2 and activating the LH mRNA expression pathway in MGC. Purple Cycle: In the cumulus granulosa cell (CGC), NPPC binds to its receptor NPR2, converting GTP into cGMP. Subsequently, cGMP diffuses into the oocyte through gap junctions (mainly Cx37), effectively inhibiting cAMP-PDE activity.

Green Cycle: The oocyte responds to paracrine factors by increasing NPR2 expression in the cumulus cells, resulting in elevated cGMP levels both in CGC and the oocyte. Additionally, the second pathway involves inosine monophosphate dehydrogenase (IMPDH) in CGC, which boosts cGMP levels through inosine-5′-monophosphate (IMP). Notably, IMPDH also maintains a basal level of hypoxanthine (HX) in the follicular fluid, potentially serving as an oocyte phosphodiesterase inhibitor to enhance intracellular cAMP accumulation for the meiotic arrest process (31).