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Stromal cell decidualization and embryo implantation: a vulnerable step leading to successful pregnancy

Reproductive and Developmental Medicine 2024年第2期8卷 101-110页

作者： Luhan Jiang Sudini R.Fernando Suranga P.Kodithuwakku Dandan Cao William S.B.Yeung Kai-Fai Lee Department of Obstetrics and Gynaecology School of Clinical MedicineLKS Faculty of MedicineThe University of Hong KongHong Kong SAR 999077China Department of Animal Science Faculty of Animal Science&Export AgricultureUva Wellassa UniversityBadulla 50000Sri Lanka Department of Animal Science Faculty of AgricultureUniversity of PeradeniyaPeradeniya 20400Sri Lanka Shenzhen Key Laboratory of Fertility Regulation.The University of Hong Kong-Shenzhen Hospital Shenzhen 518053China

Endometrial stromal cell decidualization is a crucial step in endometrial remodeling during *** is controlled by orchestrated ovarian hormones,followed by the activation of various downstream signaling *** evidence has shown multiple functions of decidualized endometrial stromal cells during embryo implantation,including tissue remodeling,antioxidative stress,angiogenesis,and immune *** distinct secretomes of decidualized stromal cells also reveal their intensive interactions with epithelial,endothelial,and immune ***,aberrant decidualization leads to pregnancy failures,such as recurrent pregnancy loss and repeated implantation *** review aimed to provide an overview of the molecular mechanisms underlying the divergent functions of decidualized endometrial stromal cells and their potential clinical ***,the use of single-cell RNA sequencing data further enhances our understanding of these biological *** review discusses decidualization-related signaling pathways that serve as potential therapeutic targets for treating implantation failure in in vitro fertilization and provides novel approaches to investigate the underlying causes of female infertility.

关键词： Endometrial stromal cell decidualization Embryo implantation Recurrent pregnancy loss Repeated implantation failure

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Unique and independent role of the GABAB1 subunit in embryo implantation and uterine decidualization in mice

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Genes & Diseases 2021年第1期8卷 79-86页

作者： Wenhao Chen Qian Zhang Haibin Wang Dongmei Tan Yi Tan Laboratory Animal Center Chongqing Medical UniversityChongqing400016PR China Reproductive Medical Center The First Affiliated Hospital of Xiamen UniversityXiamen361003FujianPR China Fujian Provincial Key Laboratory of Reproductive Health Research Medical College of Xiamen UniversityXiamen361102FujianPR China

Embryo implantation and decidualization are crucial for successful pregnancy,which include multiple genes and signaling pathways,while the precise mechanism regarding embryo implantation and decidualization has yet to be *** GABA which activates GABA_(A)or GABA_(B)receptors has been found playing an important role in early *** we seek to investigate whether GABA_(B)receptors participate in embryo implantation in *** study first characterized the spatiotemporal expression pattern of GABA_(B)receptors in the uterus during the peri-implantation period and found that GABA_(B1)expression was drastically upregulated in stromal cells on days 4e6,a period of embryo implantation and early stages of *** delayed implantation and oil-induced decidualization models were further used to confirm that the GABA_(B1)was associated with embryo implantation and *** also found estrogen or progesterone had no directly effect on expression of GABA_(B1)in ovariectomized *** we were unable to detect significant GABA_(B2)which couples with GABA_(B1)to form whole GABA_(B)receptors,and the agonist and antagonist of whole GABA_(B)receptors had weak effect on the proliferation and differentiation of stromal cells as well,we excluded the possibility whole GABA_(B)receptors function,and concluded it should be non-classical signals of GABA_(B1)involving in embryo implantation and *** studies should focus on investigating the roles and mechanisms of GABA_(B1)during embryo implantation and decidualization.

关键词： decidualization Embryo implantation Endometrial stromal cells GABAB1 Ovarian hormones Proliferation

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decidualization and Related Pregnancy Complications

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Maternal-Fetal Medicine 2022年第1期4卷 24-35页

作者： Jing Tong Shijian Lv Jieqiong Yang Hongwanyu Li Weiya Li Cong Zhang Center for Reproductive Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200135China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai200135China Shandong Provincial Key Laboratory of Animal Resistance Biology College of Life SciencesShandong Normal UniversityJinanShandong 250014China

decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal *** decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming,which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate *** extends from the primary decidual zone to the secondary decidual zone,and then exits through *** support that decidual fibroblasts function as the pool of decidual stromal cells during *** undergoes an acute inflammatory phase,an anti-inflammatory secretory phase to the final recession *** decidualization of the inner layer of endometrium,termed decidua,is the most critical determinant of pregnancy success,which can promote placenta formation,modulate immune tolerance,foster resistance to oxidative stress,sense embryo quality,and control *** to adequate decidualization in terms of hormones,biochemistry,and immunology leads to adverse pregnancy outcomes,including diseases such as preeclampsia,miscarriage,premature labor,repeated implantation failures,and some age-related decline in reproductive *** development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of ***,decidualization is a dynamic,multi-step process,and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be *** study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

关键词： Decidua decidualization Decidual stromal cells Endometrial stromal cells Pregnancy complications

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Research Progress on Human Endometrium decidualization In vitro Cell Models

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Reproductive and Developmental Medicine 2021年第2期5卷 119-127页

作者： Zhi-Jing Tang Hai-Yun Guan Lu Wang Wei Zhang Department of Reproductive Endocrinology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China

decidualization is a special type of differentiation of endometrial stromal cells into secretory decidualized cells,which is closely related to the occurrence of menstruation and establishment of *** abnormalities can cause female infertility and abortion,and the decidualization modelin vitro is an important tool for studying relevant *** article summarizes severalin vitro decidualization models in recent research from three aspects,including the selection of model cells and culture systems,evaluation of decidualization markers,and induction *** models can be appropriately selected and applied in specific endometrium-related disease models,such as endometriosis,recurrent pregnancy loss,and preeclampsia.

关键词： Cyclic Adenosine Monophosphate decidualization Endometrium Estrogen In vitro Cell Model Progestogen

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Fibroblast growth factors 7 is involved in ESCs decidualization via ERK and JNK signal pathway

Fibroblast growth factors 7 is involved in ESCs decidualizat...

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第十一届全国免疫学学术大会

作者： Zhou Wen-Jie Hospital & Institute of Obstetrics and Gynecology

Objective:decidualization is an essential preparation of human endometrium for implantation,including spatiotemporal genetic,morphological and functional changes of endometrial stromal cells(ESCs),however,the molecular mechanisms of it are not well *** growth factor(FGF) 7,which are expressed in stromal cells,proves to exert a paracrine effect during the process of implantation and has crucial proliferation *** and Methods:We did histological analysis of FGF7 in tissues of normal decidua,abnormal decidua(from RPL women) as well as normal endometrium,and examined the expression and function of FGF7 in in vitro decidualized ESCs models and various types of primary cultured stromal *** expression of FGF7 was detected in DSCs,abnormal DSCs and ESCs by *** levels of decidualization were estimated by *** ERK and JNK signaling were examined by in-cell Western in these cells with or without addition of anti-FGF7 neutralizing *** the proliferation abilities of decimalized ESCs,normal ESCs and DSCs were detected by Brd U cell proliferation assay ***:FGF7 expression in ESCs was significantly increased after decidualization stimulated by 8-Br-c AMP or the combination of progesterone and 17β-***7 stimulated the stromal cells proliferation and phosphorylation of ERK and *** the ERK and JNK pathway by using specific inhibitors(U0126 and SP600125) partly neutralized the effects of FGF7 on cells *** addition,adding anti-FGF7 neutralizing antibody amplified the existing decreased effect on cells ***:FGF7 is involved in the ESCs decidualization through the ERK and JNK signal pathway.

关键词： decidualization endometrial stromal cell(ESC) FGF7 ERK JNK

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NK cell derived IL-25 regulates the decidualization of human endometrial stromal cells

NK cell derived IL-25 regulates the decidualization of human...

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第十一届全国免疫学学术大会

作者： Zhang Yuan Wang Ying Li Mingqing Jin Liping Hospital & Insititute of Obstetrics & Gynecology Fudan University Shanghai Medical College Shanghai First Maternity and Infant Hospital Tongji University School of Medicine

Objective:To compare the expression of IL-25/IL-17 RB in endometrial stromal cells(ESC) and decidual stromal cells(DSC);to investigate the effect of IL-25 on the decidualization of the primary human endometrial stromal ***:We isolated the primary ESC and DSC from normal healthy volunteers,and detected the expression of IL-25/IL-17 RB by FCM;by stimulating ESC with c AMP plus MPA,we established the in vitro decidualization model and chose PRL and IGFBP-1 as the markers of decidualization;we compared the expression of IL-25/IL-17 RB by FCM before and after the induction of decidualization;we treated ESC by anti-IL-25 neutralizing antibody or anti-IL-17 RB neutralizing antibody,and then detected the IGFBP-1 level in the ESC by Western blot or PRL level in the supernatant by ELISA;we also isolated the decidual NK cells by MACS and identified their purity;finally we detected the IL-25 level secreted by d NK,and co-cultured d NK with ESC to detect the effect of d NK on ***:The positive percentage of IL-25/IL-17 RB on DSC was much higher than that of ESC;after the decidualization,the positive percentage of IL-25/IL-17 RB on ESC was much higher;c AMP+MPA+IL-25 could induce higher level of IGFBP-1 and PRL than c AMP+MPA alone;anti-IL-25 neutralizing antibody and anti-IL-17 RB neutralizing antibody inhibited the secretion of *** purity of d NK was 97%,and d NK could secrete IL-25 in a time-dependent manner that could upregulate the expression of decidualization marker ***:In the process of in vitro decidualization,the positive percentage of IL-25/IL-17 RB on ESC is upregulated;IL-25 expressed by ESC and d NK could enhance the decidualization further,which is a positive feedback and may promote the successful pregnancy.

关键词： IL-25 NK cells ESCs decidualization

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Maternal Smad3 Deficiency Compromises decidualization in Mice

Maternal Smad3 Deficiency Compromises Decidualization in Mic...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Kun-Qing Zhao~(1,2),Hai-Yan Lin~1,Cheng Zhu~1,Hong-Mei Wang~1 1.Reproductive Biology,Institute of Zoology,Chinese Academy of Science,Beijing 2.Graduate University,Chinese Academy of Sciences,Beijing

TGF- and Activin,which are TGF- superfamily members,are abundantly expressed in the endometrium and promote decidualization of endometrial ***2 and Smad3 are receptor-regulated Smads(R-Smads) that transduce extracellular TGF-β/Activin/Noda1 *** situ hybridization results showed that Smad3 was highly expressed in the decidual zone during the peri-implantation period in *** artificial decidualization, we found that Smad3-null mice showed compromised *** therefore suspected that Smad2 may partially compensate for the function of Smad3 during the process of ***2 was also highly expressed in the decidual zone and phosphorylated Smad2 was significantly up-regulated in the deciduoma of Smad3-null mice than that of wild-type(WT) *** further employed an in vitro uterine stromal cell decidualization model,and found that decidual prolactin-related protein(dPRP) and cyclin D3,which are well-known markers of decidual cells,were significantly down-regulated in Smad3-null decidual cells when the expression of Smad2 was silenced by siRNA(pdecidualization and suggest that Smad2 and Smad3 may have redundant roles in decidualization.

关键词： decidualization Smad3 Smad2

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Basic Research Advances in China on Embryo Implantation,Placentation,and Parturition

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Maternal-Fetal Medicine 2024年第1期6卷 37-49页

作者： Haili Bao Haibin Wang Fujian Provincial Key Laboratory of Reproductive Health Research Department of Obstetrics and GynecologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of MedicineXiamen UniversityXiamen 361102China

This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent *** was systematically searched from January 2020 to November *** that reported the progress in embryo implantation,placentation,and parturition made by Chinese scientists in the last 3 years were *** milestone events during gestation,embryo implantation,endometrial decidualization,placentation,and parturition are pivotal to a successful *** implantation requires intricate interactions between implantation-competent blastocysts and receptive *** adapt to pregnancy,endometrial stromal cells transform into specialized decidual cells,which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in *** embryonic development,the placenta forms to support fetal growth until *** maternal-fetal interface is composed of diverse cell types,including endometrial decidual cells,placental trophoblast cells,endothelial cells,and various immune cells,a sophisticated interplay among which contributes to the maintenance of *** term,the uterus transitions from quiescence to contractility,in preparation for *** to these events lead to pregnancy-related disorders such as repeated implantation failure,recurrent pregnancy loss,preeclampsia,fetal growth restriction,preterm birth,and *** recent years,Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy *** scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years,highlighting future research directions in this field.

关键词： Embryo implantation decidualization Placentation Maternal-fetal interface Parturition

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Transforming growth factor β signaling in uterine development and function

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Journal of Animal Science and Biotechnology 2015年第2期6卷 142-150页

作者： Qinglei Li Department of Veterinary Integrative Biosciences College of Veterinary Medicine and Biomedical Sciences Texas A&M UniversityCollege Station

Transforming growth factor β （TGFβ） superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

关键词： decidualization Development Embryonic development Implantation Myometrium Pregnancy Transforminq clrowth factor β. Uterus

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Activation of Uterine Smad3 Pathway Is Crucial for Embryo Implantation

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Current Medical Science 2019年第6期39卷 997-1002页

作者： Juan LI Xi-yuan DONG Pei-wen YANG Shu-lin YANG Dan HU Han-wang ZHANG Cong SUI Reproductive Medicine Center Tongji Hospital Tongji Medicine CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Gynecology Women's HospitalSchool of MedicineZhejiang UniversityHangzhou 310000China

Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth *** growth factor-betas(TGF-βs)and their most specific signal transduction factors,Smads,are expressed in the endometrium during the window of *** researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo *** this study,we measured the expression of TGF-β1,TGF-β receptor type I(TpRI),Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4,5 and 6 of *** we administrated a specific Smad3 inhibitor(Sis3)into the uterine cavity of mice on day 3 of *** results showed a reduction in insulin-like growth factor-1(IGFBP-1)expression and the decreased number of implanted embryo after the *** addition,Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal *** all together,our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.

关键词： transforming growth factor-betas(TGF-βs) Smad3 endometrial receptivity decidualization embryo implantation

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