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Meiotic Arrest in Human Oocytes Is Maintained by a G_s Signaling Pathway¹

Department of Cell Biology³ and Center for Advanced Reproductive Services,⁴ University of Connecticut Health Center, Farmington, Connecticut 06030

ABSTRACT

In mammalian oocytes, the maintenance of meiotic prophase I arrest prior to the surge of LH that stimulates meiotic maturation depends on a high level of cAMP within the oocyte. In mouse and rat, the cAMP is generated in the oocyte, and this requires the activity of a constitutively active, G_s–linked receptor, GPR3 or GPR12, respectively. To examine if human oocyte meiotic arrest depends on a similar pathway, we used RT-PCR and Western blotting to look at whether human oocytes express the same components for maintaining arrest as rodent oocytes. RNA encoding GPR3, but not GPR12, was expressed. RNA encoding adenylate cyclase type 3, which is the major adenylate cyclase required for maintaining meiotic arrest in the mouse oocyte, was also expressed, as was G_s protein. To determine if this pathway is functional in the human oocyte, we examined the effect of injecting a function-blocking antibody against G_s on meiotic resumption. This antibody stimulated meiotic resumption of human oocytes that were maintained at the prophase I stage using a phosphodiesterase inhibitor. These results demonstrate that human oocytes maintain meiotic arrest prior to the LH surge using a signaling pathway similar to that of rodent oocytes.

cyclic adenosine monophosphate, gamete biology, signal transduction

¹Supported by grants HD056366 and the Center for Interdisciplinary Research in Women's Health at the University of Connecticut Health Center to L.M.M. and DK073499 to L.A. Jaffe.

Correspondence: ²Lisa M. Mehlmann, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030. FAX: 860 679 1269; e-mail: lmehlman{at}neuron.uchc.edu