Fig. 2

A abbreviated pathway depicting the participation of FSH/FHSR, Estrogen/ER, NPPC/NPR2, Oocyte in maintaining mammalian oocyte meiotic arrest. [1] In the mural granulosa cells, FSH binds its GPR receptor (FSHR), collaborating with Estrogen/ER signal pathway prompts NPPC production [72, 91, 103]. [2] In the cumulus granulosa cell, NPPC actives its receptor NPR2, converts GTP into cGMP, then cGMP diffuses into the oocyte through gap junctions (mainly Cx37) inhibits cAMP-PDE activity, blocks the degradation of intraoocyte cAMP [84, 104]. [3] The oocyte-derived paracrine factors increase cumulus cell NPR2 expression leads to an elevated cGMP level in both cumulus granulosa cell and oocyte; In addition, IMPDH is increased, converts IMP to GMP, to provide more substrates required to produce guanylyl metabolites and cGMP in the cumulus granulosa cell; Furthermore, the increased IMPDH maintains the basal level of HX in the follicular fluid, which might act as an oocyte phosphodiesterase inhibitor to augment the meiotic arrest and intracellular cAMP accumulation [95, 105]. ER: G protein-coupled estrogen receptor; IMPDH: inosine monophosphate dehydrogenase; IMP: inosine-5′-monophosphate; HX: hypoxanthine