Dysfunction of Shh signaling activates autophagy to inhibit trophoblast motility in recurrent miscarriage |
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| Authors: | Yibin Pan Lili Yan Qiaoqiao Chen Cheng Wei Yongdong Dai Xiaomei Tong Haiyan Zhu Meifei Lu Yanling Zhang Xiaoying Jin Tai Zhang Xiaona Lin Feng Zhou Songying Zhang |
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| Institution: | 1.Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China ;2.Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, China ;3.Beilun District Hospital of Traditional Chinese Medicine, Ningbo City, Zhejiang China ;4.Department of Pharmacy, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China |
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| Abstract: | In early pregnancy, the placenta anchors the conceptus and supports embryonic development and survival. This study aimed to investigate the underlying functions of Shh signaling in recurrent miscarriage (RM), a serious disorder of pregnancy. In the present study, Shh and Gli2 were mainly observed in cytotrophoblasts (CTBs), Ptch was mainly observed in syncytiotrophoblasts (STBs), and Smo and Gli3 were expressed in both CTBs and STBs. Shh signaling was significantly impaired in human placenta tissue from recurrent miscarriage patients compared to that of gestational age-matched normal controls. VEGF-A and CD31 protein levels were also significantly decreased in recurrent miscarriage patients. Furthermore, inhibition of Shh signaling impaired the motility of JAR cells by regulating the expression of Gli2 and Gli3. Intriguingly, inhibition of Shh signaling also triggered autophagy and autolysosome accumulation. Additionally, knockdown of BECN1 reversed Gant61-induced motility inhibition. In conclusion, our results showed that dysfunction of Shh signaling activated autophagy to inhibit trophoblast motility, which suggests the Shh pathway and autophagy as potential targets for RM therapy.Subject terms: Embryology, Endocrine reproductive disorders, Autophagosomes |
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