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Imbalance of Amniotic Fluid Activin-A and Follistatin in Intraamniotic Infection, Inflammation, and Preterm Birth

John T Hardy1, Irina A Buhimschi1, Megan E McCarthy1

  • 1Department of Obstetrics/Gynecology and Reproductive Sciences (J.T.H., M.E.M., C.A.L., L.L.S.), Yale University School of Medicine, New Haven, Connecticut 06520; Center for Perinatal Research (I.A.B., G.Z.), The Research Institute at Nationwide Children's Hospital, and Department of Pediatrics (I.A.B.), The Ohio State University College of Medicine, Columbus, Ohio 43215; and Department of Obstetrics/Gynecology (I.A.B., C.S.B.), The Ohio State University College of Medicine, Columbus, Ohio 43210.

The Journal of Clinical Endocrinology and Metabolism
|May 10, 2016
PubMed
Abstract

Insights

Activin-A and follistatin in amniotic fluid influence preterm birth (PTB) by modulating inflammatory pathways. An imbalanced activin-A to follistatin ratio, especially during infection, correlates with PTB and preterm premature rupture of membranes (PPROM).

Area of Science:

  • Reproductive biology
  • Maternal-fetal medicine
  • Inflammation research

Background:

  • Microbial invasion of amniotic fluid triggers inflammation involving activin-A.
  • Follistatin, an activin-A inhibitor, is present in amniotic fluid, but its role in inflammation-induced preterm birth (PTB) is unclear.

Purpose of the Study:

  • Investigate the relationship between activin-A and follistatin in amniotic fluid during normal and preterm labor.
  • Evaluate the role of the activin-A-follistatin balance in PTB and preterm premature rupture of membranes (PPROM).

Main Methods:

  • Immunoassay of amniotic fluid activin-A and follistatin in 168 women.
  • In vitro study using amniochorion explants challenged with lipopolysaccharide (LPS) to assess the impact of activin-A/follistatin imbalance on PTB pathways.

Main Results:

  • Amniotic fluid follistatin and the activin-A to follistatin ratio decrease with gestational age.
  • Infection elevates activin-A and the activin-A/follistatin ratio, correlating with inflammation severity.
  • Activin-A upregulates prostaglandins and matrix metalloproteinases (MMPs); follistatin partially counteracts these effects.

Conclusions:

  • Activin-A and follistatin are key components of the gestational sac's inflammatory response to infection.
  • The activin-A to follistatin ratio may influence the clinical presentation of PTB, such as preterm labor or PPROM.

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