pp 1–11 | Cite as

Role of the small proteoglycan bikunin in human reproduction

  • Antonio Junior Lepedda
  • Pierina De Muro
  • Giampiero CapobiancoEmail author
  • Marilena FormatoEmail author
Review Article



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.


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.


Bikunin is a small chondroitin sulfate proteoglycan found in blood, urine, and amniotic and cerebrospinal fluids, known for its anti-inflammatory and anti-proteolytic 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 preterm delivery, pre-eclampsia, and gestational diabetes mellitus. Finally, its intravaginal administration has been reported to reduce the risk of preterm delivery and to improve neonatal outcomes.


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 preterm delivery and improving neonatal outcomes have yielded interesting results that deserve to be investigated through further research.


Bikunin Human reproduction Extracellular matrix stabilization Inhibitor of uterine contractions Anti-inflammatory agent Anti-proteolytic agent 



AJ Lepedda thanks Regione Autonoma della Sardegna for its financial support (POR - FSE 2014–2020 - Asse Prioritario 3 “Istruzione e Formazione” – Obiettivo tematico: 10, Priorità d’investimento: 10ii, Obiettivo specifico: 10.5, Azione dell’Accordo di Partenariato 10.5.12 - C.U.P. J86C18000270002).

Ph. Doctor School in Biomedical Sciences, Address in Gender Medicine, Men, Woman and Child, Sassari University, Italy, supported the study

The authors thank the University of Sassari for its financial support (fondo di Ateneo per la ricerca 2019).

Author contribution

A.J. Lepedda: project development, data collection, manuscript writing/editing, and figure drawing/editing

P. De Muro: data collection, manuscript editing, and figure editing

G. Capobianco: project development, data management, and manuscript editing

M. Formato: manuscript writing/editing

Compliance with ethical standards

Conflict of interest

The authors (Antonio J. Lepedda, Pierina De Muro, Giampiero Capobianco, and Marilena Formato) declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not needed for review manuscript.


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© Hellenic Endocrine Society 2019

Authors and Affiliations

  1. 1.Department of Biomedical SciencesUniversity of SassariSassariItaly
  2. 2.Gynecologic and Obstetric Clinic, Department of Medical, Surgical and Experimental SciencesUniversity of SassariSassariItaly

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