Modulation of Amniotic Fluid Activin-A and Inhibin-A in Women With Preterm Premature Rupture of the Membranes and Infection-Induced Preterm Birth


Catalin S. Buhimschi, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, 333 Cedar Street, LLCI 804, New Haven, CT 06520, USA.


Citation Rosenberg VA, Buhimschi IA, Dulay AT, Abdel-Razeq SS, Oliver EA, Duzyj CM, Lipkind H, Pettker CM, Buhimschi CS. Modulation of amniotic fluid activin-A and inhibin-A in women with preterm premature rupture of the membranes and infection-induced preterm birth. Am J Reprod Immunol 2012; 67: 122–131

Problem  Activins and inhibins are important modulators of inflammatory processes. We explored activation of amniotic fluid (AF) activin-A and inhibin-A system in women with intra-amniotic infection and preterm premature rupture of the membranes (PPROM).

Method of study  We analyzed 78 AF samples: ‘2nd trimester-control’ (n = 12), ‘3rd trimester-control’ (n = 14), preterm labor with intact membranes [positive-AF-cultures (n = 13), negative-AF-cultures (n = 13)], and PPROM [positive-AF-cultures (n = 13), negative-AF-cultures (n = 13)]. Activin-A levels were evaluated ex-vivo following incubation of amniochorion and placental villous explants with Gram-negative lipopolysaccharide (LPS) or Gram-positive (Pam3Cys) bacterial mimics. Ability of recombinant activin-A and inhibin-A to modulate inflammatory reactions in fetal membranes was explored through explants’ IL-8 release.

Results  Activin-A and inhibin-A were present in human AF and were gestational age-regulated. Activin-A was significantly upregulated by infection. Lower inhibin-A levels were seen in PPROM. LPS elicited release of activin-A from amniochorion, but not from villous explants. Recombinant activin-A stimulated IL-8 release from amniochorion, an effect that was not reversed by inhibin-A.

Conclusion  Human AF activin-A and inhibin-A are involved in biological processes linked to intra-amniotic infection/inflammation-induced preterm birth.