Role of the small proteoglycan bikunin in human reproduction

Purpose: Female reproductive events, including ovulation, menstruation, implantation, and delivery, are physiologically characterized by deep tissue remodeling and display hallmark signs of inflammation. This review discusses the pleiotropic roles played by bikunin in human reproduction. Methods: A comprehensive literature search of the Medline/PubMed database was performed on the following topics: bikunin structure, roles in pathophysiological conditions and involvement in human reproduction, and usefulness as a marker of gestational complications or as a drug to improve pregnancy outcomes. Results: Bikunin is a small chondroitin sulfate proteoglycan found in blood, urine, and amniotic and cerebrospinal fluids, known for its anti-inflammatory and antiproteolytic activities. Its levels are usually low, but they can increase several-fold in both acute and chronic inflammatory diseases. Bikunin plays key roles in reproductive events, such as cumulus oocyte complex formation, pregnancy, and delivery. Its levels have been associated with the most common pregnancy complications such as pre-term delivery, pre-eclampsia, and gestational diabetes mellitus. Finally, its intravaginal administration has been reported to reduce the risk of pre-term delivery and to improve neonatal outcomes. Conclusions: Because of its pleiotropic roles in several reproductive events and its association with some life-threatening pathological conditions of pregnancy, bikunin may represent a non-invasive marker for improving follow-up and early diagnosis. Studies showing its usefulness as a drug for reducing the risk of pre-term delivery and improving neonatal outcomes have yielded interesting results that deserve to be investigated through further research.