| First Author | Erpenbeck L | Year | 2016 |
| Journal | Biol Reprod | Volume | 95 |
| Issue | 6 | Pages | 132 |
| PubMed ID | 28007693 | Mgi Jnum | J:238266 |
| Mgi Id | MGI:5818978 | Doi | 10.1095/biolreprod.116.140293 |
| Citation | Erpenbeck L, et al. (2016) PAD4 Deficiency Decreases Inflammation and Susceptibility to Pregnancy Loss in a Mouse Model. Biol Reprod 95(6):132 |
| abstractText | Inflammation is thought to play a critical role in the pathogenesis of placentation disorders such as recurrent miscarriages, growth restriction, and preeclampsia. Recently, neutrophil extracellular traps (NETs) have emerged as a potential mechanism for promoting inflammation in both infectious and noninfectious disorders. To investigate a pathogenic role for NETs in placentation disorders, we studied a model of antiangiogenic factor-mediated pregnancy loss in wild-type (WT) mice and in mice deficient in peptidylarginine deiminase 4 (Padi4-/-) that are unable to form NETs. Overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), an antiangiogenic protein that is pathogenically linked with abnormal placentation disorders during early gestation, resulted in pregnancy loss and large accumulation of neutrophils and NETs in WT placentas. Interestingly, sFlt-1 overexpression in Padi4-/- mice resulted in dramatically lower inflammatory and thrombotic response, which was accompanied by significant reduction in pregnancy losses. Inhibition of NETosis may serve as a novel target in disorders of impaired placentation. |
