Endothelin-2 in ovarian follicle rupture.
ABSTRACT The ovulatory process is activated by a surge of LH, a pituitary gonadotropin, which initiates a cohort of dramatic changes in biochemical, physical, and gene expression in the ovary, leading to follicle rupture and oocyte release. Here we report the identification of endothelin-2 (EDN2) as a last moment-trigger of follicle rupture. In the ovary, EDN2 is exclusively and transiently expressed in the granulosa cells immediately before ovulation. Administration of EDN2 to the ovarian tissue induced rapid contraction, whereas addition of tezosentan, an endothelin receptor antagonist, diminishes the EDN2 effect. In vivo, treatment of tezosentan before ovulation substantially decreases gonadotropin-induced superovulation. As a target tissue of EDN2 action, we identified a layer of smooth muscle cells in the follicular wall of each follicle. Taken together, our data indicate that EDN2 induces follicular rupture by constricting periovulatory follicles.
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ABSTRACT: Ovulation is stimulated by the preovulatory surge of the pituitary luteinizing hormone (LH). Because the ovulatory response is commonly identified with inflammation, we explored the involvement of reactive oxygen species (ROS) in this process. Our experiments show that administration of broad-range scavengers of oxidative species into the ovarian bursa of mice, hormonally induced to ovulate, significantly reduced the rate of ovulation. LH-induced cumulus mucification/expansion, a necessary requirement for ovulation, was prevented by antioxidants both in vivo and in an ex vivo system of isolated intact ovarian follicles. Along this line, H(2)O(2) fully mimicked the effect of LH, bringing about an extensive mucification/expansion of the follicle-enclosed cumulus-oocyte complexes. Impaired progesterone production was observed in isolated follicles incubated with LH in the presence of the antioxidant agents. Furthermore, LH-stimulated up-regulation of genes, the expression of which is crucial for ovulation, was substantially attenuated upon ROS ablation. This system was also used for demonstrating the role of ROS in phosphorylation and activation of the EGF receptor as well as its downstream effector, p42/44 MAPK. Together, our results provide evidence that ovarian production of ROS is an essential preovulatory signaling event, most probably transiently triggered by LH.Proceedings of the National Academy of Sciences 01/2011; 108(4):1462-7. · 9.68 Impact Factor
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ABSTRACT: Optimal maturation of oocytes and successful development of preimplantation embryos is essential for reproduction. Mammalian oocytes remain dormant in the diplotene stage of prophase I until the resumption of meiosis characterized by germinal vesicle breakdown (GVBD) following preovulatory gonadotropin stimulation. In response to the preovulatory luteinizing hormone (LH) increase, oocytes undergo GVBD, followed by first polar body extrusion. Although the preovulatory surge of LH is the primary event responsible for the induction of maturation of the oocyte, LH does not act directly on the oocyte due to the absence of functional LH receptors in germ cells. Instead, actions of LH are mediated either by paracrine factors secreted by LH-responsive somatic cells or by the transport of cellular messengers from granulosa/cumulus cells to oocytes through intercellular gap junctions. In addition to the nuclear maturation exemplified by GVBD and extrusion of the first polar body to complete the first meiotic division, oocytes also undergo cytoplasmic maturation characterized by cytoplasmic changes essential for monospermic fertilization, processing of the sperm, and preparation for development to preimplantation embryos. In this review, we summarize our recent works on the identification and characterization of novel LH-inducible ovarian factors for nuclear and cytoplasmic maturation of oocytes.Journal of Mammalian Ova Research 06/2011;