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. |