The resumption of meiosis mediated by angiotensin II is dependent on progesterone, oxytocin and prostaglandin
Gonçalves, Paulo BayardBarreta, Marcos HenriqueOliveira, João FranciscoFerreira, RogérioGasperin, Bernardo GarzieraSiqueira, Lucas Carvalho
Background: Oocytes are arrested in the first meiotic prophase during follicular development until near ovulation. In vitro, oocytes resume meiosis spontaneously, germinal vesicle breakdown (GVBD) occurs and oocytes progress to the MII stage when they are removed from their follicles and cultured under suitable conditions. On the other hand, meiotic maturation of bovine oocytes occurs within the follicle, raising the question regarding possible involvement of positive signal(s) to induce meiotic resumption in vivo. Meiotic resumption is dependent on the preovulatory surge of LH, but the bovine cumulusoocyte complexes (COCs) do not have LH receptors, so the signal must occur through theca and mural granulosa cells. The LH surge stimulated the ovarian renin-angiotensin system (RAS), including an increase in the renin activity and angiotensin II (AngII) concentration in bovine follicular fluid. Also, the interactions among LH, AngII increased follicular production of prostaglandins (PGs) and modulated steroidogenesis in the bovine preovulatory follicle. AngII has also been associated with follicular growth and ovulation in cows. Furthermore, AngII stimulated the resumption of meiosis in co-culture systems of cumulus enclosed bovine oocytes and follicular cells. Review: The presence of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II (Ang II) and Ang II receptors in the ovary is suggestive of a functional ovarian RAS. In the last few years, our research group has focused on studying the contribution of RAS in antral follicle development, ovulation and oocyte maturation. A new concept of mechanism and factors involved in oocyte meiotic resumption has been established using cattle as a model. Transvaginal ultrasound has been used for intrafollicular injection to investigate factors that play a part in the resumption of meiosis. With this in vivo and an in vitro model, culturing oocytes in the presence of theca and granulosa cells, we have demonstrated that AngII via the AT2 receptor subtype plays a pivotal role in the antral follicle development, early mechanism of ovulation and oocyte meiotic resumption in cattle. When bovine cumulus-oocyte complexes (COCs) are cultured with follicular hemisections, oocyte maturation is inhibited; however, follicular cells or conditioned medium were unable to inhibit nuclear maturation in the presence of AngII. In vivo, intrafollicular injection of saralasin (a competitive AngII antagonist) completely inhibited the oocyte meiotic resumption in follicles (larger than 12 mm) challenged with an GnRH agonist. Moreover, oocytes co-cultured with follicular hemisections progressed nuclear maturation when prostaglandin E2 (PGE2), PGF2a, progesterone, oxitocin or AngII was present in the coculture system and indomethacin inhibited AngII-induced meiotic resumption. Conclusion: our results provide strong evidence that AngII mediates the oocyte meiotic resumption induced by an LH surge in cattle and that this event is dependent on progesterone, oxytocin and prostaglandin.
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