Meiotic state of bovine oocytes is regulated by interactions between cAMP, cumulus, and granulosa.

Bovine oocytes are arrested at the prophase of first meiotic cell cycle. Meiosis resumes in oocytes of pre-ovulatory follicles upon LH surge. However, oocytes from secondary follicles spontaneously resume meiosis in the absence of hormones if removed from the follicle and cultured in vitro. The nature of meiotic arrestor in bovine follicles is poorly understood. In this study we investigated the role of cell-cell interactions between granulosa and cumulus cells and the oocyte in mediating maintenance of meiotic arrest by cAMP. We sorted oocytes as granulosa-cumulus oocyte complexes (GCOC) if surrounded with cumulus cells attached to a large granulosa investment or cumulus oocytes complexes (COC) if surrounded with cumulus cells only and investigated the role cAMP in maintenance of meiotic arrest in these oocytes under various conditions. In hormone- and serum-free medium both GCOC and COC enclosed oocytes resumed meiosis. When [cAMP](i) was elevated with addition of invasive adenylate cyclase (iAC) GCOC enclosed oocytes were maintained in the prophase with intact germinal vesicle (GV) while COC enclosed oocytes underwent GV breakdown (GVBD). iAC elevated [cAMP](i) in both types of oocytes to the same level. If oocytes were liberated from the cumulus and granulosa cells, they re-initiated meiosis in serum and hormone free medium, but remained in the GV stage if iAC was added to the medium. Untreated GCOC and COC enclosed oocytes extruded first polar body at the same frequency in hormone-supplemented media. GCOC and COC enclosed oocytes but not denuded oocytes (DO) cultured without somatic cells acquired developmental competence if cultured in hormone-containing medium. It is concluded that maintenance of meiotic arrest is regulated by the interplay of [cAMP](i), and cumulus and granulosa cells.

Aktas H ，Leibfried-Rutledge ML ，First NL 《MOLECULAR REPRODUCTION AND DEVELOPMENT》

Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation.

The differential regulation of cAMP levels within the oocyte and somatic (cumulus) cell compartments of the bovine follicle, and the subsequent regulation of oocyte meiotic maturation was examined through specific cell-type localisation of phosphodiesterases (PDEs). Selective PDE inhibitors were used to modulate cAMP levels in each of the two follicular compartments and to examine their effects on oocyte meiotic maturation. Ovaries were obtained from an abattoir and cumulus-oocyte complexes (COC) were aspirated from antral follicles into culture medium supplemented with 4 mg/ml BSA and 2mM 3-isobutyl-1-methylxanthine (IBMX). COC, denuded oocytes (DO), or mural granulosa cells (MGC) were cultured either with or without forskolin or FSH, in the presence of specific PDE inhibitors; either milrinone (PDE3 inhibitor), cilostamide (PDE3 inhibitor), or rolipram (PDE4 inhibitor). COC/DO cultures were assessed for meiotic progression and cAMP content, and MGC for cAMP production. The type 3 PDE inhibitor, but not the type 4, prevented spontaneous meiotic maturation and elevated intraoocyte cAMP in cultured denuded oocytes. In contrast, the type 4 PDE inhibitor had no effect on the oocyte, but elevated mural granulosa and cumulus cell cAMP production. The results of this study indicate that specific PDE subtypes are differentially localised within the two compartments of the bovine follicle-the type 3 PDE in the oocyte and the type 4 PDE in the granulosa cells. In addition, oocyte cAMP levels are primarily regulated in bovine oocytes by its degradation by PDE, whereas granulosa cell cAMP levels are controlled mainly by active adenylate cyclase, with both sources able to participate in oocyte meiotic regulation.

Thomas RE ，Armstrong DT ，Gilchrist RB 《DEVELOPMENTAL BIOLOGY》

Regulation of the development of meiotic competence and of the resumption of oocyte maturation in the rat.

Tsafriri A ，Pomerantz SH 《-》

The releasing action of calcium upon cyclic AMP-dependent meiotic arrest in hamster oocytes.

Racowsky C 《-》

Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa.

van Tol HT ，van Eijk MJ ，Mummery CL ，van den Hurk R ，Bevers MM ... -  《MOLECULAR REPRODUCTION AND DEVELOPMENT》