Chemokines and human reproduction

To review the available information regarding chemotactic cytokines and their possible implications in human reproduction.

A thorough literature and MEDLINE search was conducted to identify studies relating to the role of chemokines in ovulation, menstruation, implantation, cervical ripening and preterm labor, and endometriosis.

Chemokines mediate leukocyte traffic through their specific receptors in various tissues. Although four families have been described to date, two remain the major subfamilies: alpha-chemokines (with interleukin-8 as representative for this group), and beta-chemokines (with monocyte chemotactic protein-1 as representative). Interleukin-8, monocyte chemotactic protein-1, and growth-regulated oncogene-alpha are involved in follicular development and atresia, ovulation, steroidogenesis, and corpus luteum function. Interleukin-8 showed cycle-dependent expression in human endometrium, and at the same time, stimulated endometrial stromal cell growth, acting as an autocrine growth factor. Interleukin-8 has been identified in human amnion, chorion, decidua, and villous placenta, and its level increases during labor. Levels of interleukin-8 correlate with the release of collagenases, a crucial step that regulates the process of cervical extracellular matrix remodeling. The levels of monocyte chemotactic protein-1; regulated on activation, normal T-expressed and secreted (RANTES); interleukin-8; and growth-regulated oncogene-alpha are elevated in the peritoneal fluid of women with endometriosis, and they correlate with the stage of the disease.

Chemokines play a relevant role in many physiologic and pathologic situations, such as ovulation, menstruation, implantation, cervical ripening and preterm labor, and endometriosis. Their regulation soon may provide new therapeutic strategies.