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The Role of C5a Receptor Signaling in Endotoxin‐Induced Miscarriage and Preterm Birth
Author(s) -
Denny Kerina J.,
Coulthard Liam G.,
Mantovani Susanna,
Simmons David,
Taylor Stephen M.,
Woodruff Trent M.
Publication year - 2015
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12386
Subject(s) - gestation , miscarriage , medicine , c5a receptor , fetus , pregnancy , lipopolysaccharide , premature birth , recurrent miscarriage , knockout mouse , complement system , gestational age , immunology , andrology , receptor , physiology , biology , immune system , genetics
Problem Complement factor 5a (C5a), a potent pro‐inflammatory mediator of the complement system, has been implicated in fetal rejection throughout gestation, from miscarriage to preterm birth. This study aimed to investigate the role of the principal C5a receptor, C5aR1 ( CD 88), in both miscarriage and preterm birth, in a bacterial endotoxin (lipopolysaccharide; LPS ) murine model. Method of study Wild‐type and C5ar1 knockout mice were administered LPS at 9.5 or 15.5 days post‐conception to induce miscarriage or preterm birth, respectively. Results C5ar1 knockout mice were protected against miscarriage in response to administration of LPS in early gestation. However, the absence of C5aR1 had no effect on the rates of preterm birth when LPS was administered in late gestation. Conclusion There may be a gestational window in which excessive activation of C5a can exert deleterious effects in pregnancy. Future strategies targeting the C5a‐C5aR1 signaling axis should be considered to ameliorate miscarriages in patients with recurrent pregnancy loss.