title: Timely interaction between prostaglandin and chemokine signaling is a prerequisite for successful fertilization.
abstract: Timely interaction between the egg and sperm is required for successful fertilization; however, little is known about the signaling therein. Prostaglandin (PG) E receptor EP2-deficient (Ptger2(-/-)) female mice exhibit a severe fertilization defect. We investigated the molecular events leading to this failure. We found increased gene expression for chemokines, such as Ccl2, Ccl7, and Ccl9, in Ptger2(-/-) cumulus cells (the somatic cells surrounding the egg) compared with wild-type cells. Furthermore, under physiological conditions, cumulus-derived chemokine signaling was found to have a dual action; CCL7 facilitates sperm migration to the cumulus-egg complex and integrin-mediated cumulus extracellular matrix (ECM) assembly to protect eggs. However, in the absence of PGE(2)-EP2 signaling, chronic CCL7 signaling results in excessive integrin engagement to the ECM, making the cumulus ECM resistant to sperm hyaluronidase, thereby preventing sperm penetration. Our findings indicate that PGE(2)-EP2 signaling negatively regulates the autocrine action of chemokines and prevents excessive cumulus ECM assembly. This interaction between PG and chemokine signaling is required for successful fertilization.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Shigero
authors.initials: S
authors.lastname: Tamba
authors.forename: Rieko
authors.initials: R
authors.lastname: Yodoi
authors.forename: Eri
authors.initials: E
authors.lastname: Segi-Nishida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D054885:Cumulus Cells / Q000378:metabolism; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005786:Gene Expression Regulation; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008297:Male; D051379:Mice; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction; D013094:Spermatozoa / Q000502:physiology; D013997:Time Factors
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D016023:Integrins; D011453:Prostaglandins; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D006821:Hyaluronoglucosaminidase
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