Abnormal ciliogenesis in decidual stromal cells in recurrent miscarriage

Abstract

Primary cilia regulate cellular signaling and are involved in both sensing and transducing extracellular stimuli. A recent study of patients with recurrent miscarriage (RM) identified mutations affecting DYNC2H1, which were involved in ciliary biogenesis. However, there has been no study concerning primary cilia in the decidua. We compared the number and the length of primary cilia in the decidua of 15 patients with unexplained RM with those of 7 pregnant controls who underwent an artificial termination of pregnancy. Immunohistochemistry was performed using antibodies against primary cilia, extravillous trophoblasts (EVTs), macrophages, uterine Natural Killer (uNK) cells, decidual stromal cells, and the activation of TGF-β and CREB signaling in the decidua of early pregnancy was studied. The density of decidual stromal cells, but not EVTs, macrophages or uNK cells, was found to be significantly higher in the decidua of patients compared to controls. The percentage of ciliated decidual stromal cells was significantly decreased in patients. There was no difference in the primary ciliary length. Regarding TGF-β signaling, p-Smad2 in these cells was diminished significantly in patients, and most of the TGF-β-activated decidual stromal cells of both patients and controls had primary cilia. No difference in the activation of CREB was found. Abnormal primary cilia on decidual stromal cells may be one of the explanatory factors for unknown RM. The inactivation of TGF-β signaling may lead to abnormal ciliogenesis in the decidua.