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This Article Full Text Full Text (PDF) All Versions of this Article: 78/6/1111    most recent biolreprod.107.065490v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sela-Abramovich, S. Articles by Dekel, N. PubMed PubMed Citation Articles by Sela-Abramovich, S. Articles by Dekel, N. Agricola Articles by Sela-Abramovich, S. Articles by Dekel, N.

Inhibition of Rat Oocyte Maturation and Ovulation by Nitric Oxide: Mechanism of Action¹

Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel

ABSTRACT

Established gap junctional communication (GJC) in the ovarian follicle is essential for maintaining the oocytes in meiotic arrest. Alternatively, LH-induced reinitiation of meiosis is subsequent to breakdown of GJC. It was recently reported that nitric oxide (NO) inhibits maturation in rat follicle-enclosed oocytes and elevates GJC in cultured mesangial cells. Taking these observations into account, we hypothesized that NO prevents reinitiation of meiosis by antagonizing the effect of LH on GJC in the ovarian follicle. Indeed, we found that NO interferes with LH-induced disruption of GJC as well as with the decrease of the expression of the gap junction protein GJA1 (previously known as CONNEXIN43). We also demonstrated that NO prevents activation of LH-induced mitogen-activated protein kinases (MAPKs) 1 and 2 and inhibits cumulus expansion. Along this line, incubation of ovarian follicles with an inhibitor of soluble guanylate cyclase, which is a downstream NO effector, induced on its own oocyte maturation as well as cumulus expansion. Unlike previous studies, we show here that elevation of NO resulted in inhibition of ovulation. We conclude that the mechanism by which NO inhibits LH-induced oocyte maturation possibly involves a negative effect on MAPK activation and, in turn, interference with interruption of GJC. This action of NO in the ovarian follicle is apparently mediated by cGMP. In addition, the negative effect of NO on ovulation may be subsequent to its inhibitory effect on cumulus expansion. Together, this study suggests that the preovulatory decrease in NO concentrations is a prerequisite for the ovarian response to LH.

follicle, gap junction, luteinizing hormone, nitric oxide, oocyte, ovarian follicle, ovulation

¹Supported by the Dwek Fund for Biomedical Research. N.D. is the incumbent of the Phillip M. Klutznick Professorial Chair of Developmental Biology.

Correspondence: ²Nava Dekel, Department of Biological Regulation, 15 Weizmann Institute of Science, Rehovot 76100, Israel. FAX: 972 8 934 4116; e-mail: nava.dekel{at}weizmann.ac.il