Chemokines and human reproduction

Objective: To review the available information regarding chemotactic cytokines and their possible implications in human reproduction. Design: 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. Result(s): Chemokines mediate leukocyte traffic through their specific receptors in various tissues. Although four families have been described to date, two remain the major subfamilies: α-chemokines (with interleukin-8 as representative for this group), and β-chemokines (with monocyte chemotactic protein-1 as representative). Interleukin-8, monocyte chemotactic protein-1, and growth-regulated oncogene-α 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-α are elevated in the peritoneal fluid of women with endometriosis, and they correlate with the stage of the disease. Conclusion(s): 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.