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Publication : Timely interaction between prostaglandin and chemokine signaling is a prerequisite for successful fertilization.

First Author  Tamba S Year  2008
Journal  Proc Natl Acad Sci U S A Volume  105
Issue  38 Pages  14539-44
PubMed ID  18794532 Mgi Jnum  J:142585
Mgi Id  MGI:3821796 Doi  10.1073/pnas.0805699105
Citation  Tamba S, et al. (2008) Timely interaction between prostaglandin and chemokine signaling is a prerequisite for successful fertilization. Proc Natl Acad Sci U S A 105(38):14539-44
abstractText  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.
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