Beschreibung:
<jats:p>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 (<jats:italic>Ptger2</jats:italic><jats:sup>−/−</jats:sup>) 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<jats:italic>Ccl2</jats:italic>,<jats:italic>Ccl7</jats:italic>, and<jats:italic>Ccl9</jats:italic>, in<jats:italic>Ptger2</jats:italic><jats:sup>−/−</jats:sup>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<jats:sub>2</jats:sub>-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<jats:sub>2</jats:sub>-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.</jats:p>