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Diane M. Duffy1,5,*, CheMyong Ko2,5, Misung Jo3,5, Mats Brannstrom4,5, Thomas E. Curry, Jr.3,5
1 Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23501
2 Department of Comparative Biosciences, University of Illinois Urbana Champaign, Urbana, IL 61802
3 Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40536
4 Department of Obstetrics and Gynecology, University of Gothenburg, Gothenburg, and Stockholm IVF, Stockholm, Sweden
5 All authors contributed equally to the preparation of this manuscript.
*Corresponding Author and Reprint Requests: Diane M. Duffy, PhD, Department of Physiological Sciences, PO Box 1980, Eastern Virginia Medical School, Norfolk, VA 23501-1980
Abstract
The midcycle surge of luteinizing hormone (LH) sets in motion interconnected networks of signaling cascades to bring about rupture of the follicle and release of the oocyte during ovulation. Many mediators of these LH-induced signaling cascades are associated with inflammation, leading to the postulate that ovulation is similar to an inflammatory response. First responders to the LH surge are granulosa and theca cells, which produce steroids, prostaglandins, chemokines, and cytokines, which are also mediators of inflammatory processes. These mediators, in turn, activate both nonimmune ovarian cells as well as resident immune cells within the ovary; additional immune cells are also attracted to the ovary. Together, these cells regulate proteolytic pathways to reorganize the follicular stroma, disrupt the granulosa cell basal lamina, and facilitate invasion of vascular endothelial cells. LH-induced mediators initiate cumulus expansion and cumulus oocyte complex detachment, while the follicular apex undergoes extensive extracellular matrix remodeling and a loss of the surface epithelium. The remainder of the follicle undergoes rapid angiogenesis and functional differentiation of granulosa and theca cells. Ultimately, these functional and structural changes culminate in follicular rupture and oocyte release. Throughout the ovulatory process, the importance of inflammatory responses is highlighted by the commonalities and similarities between many of these events associated with ovulation and inflammation. However, ovulation includes processes that are distinct from inflammation, such as regulation of steroid action, oocyte maturation and the eventual release of the oocyte. This review will focus on the commonalities between inflammatory responses and the process of ovulation.
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