期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 38, 页码 14539-14544出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805699105
关键词
cumulus cells; extracellular matrix; fibronectin; integrin; prostanoid receptor EP2
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health and Labor of Japan
- National Institute of Biomedical Innovation of Japan
- Japan Society for the Promotion of Science for Young Scientists
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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