Objective: The maternal–fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus. The interaction between decidual γδ Τ cells and trophoblasts plays a pivotal role during successful pregnancy; however, their physiological functions in early-term human pregnancy are still not completely illustrated. This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidual γδ T cells and HTR8/SVneo trophoblast cells. Methods: The percentile of CXCR6+ γδ T cells in the peripheral blood from normal female and recurrent spontaneous abortion (RSA) patients was analyzed by flow cytometry. The expression of CXCR6 was detected in decidual immune cells via flow cytometry, and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus (LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells. Expression of granzyme B and cytokines and proliferation of decidual γδ T cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry. Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay. Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss. Results: The percentile of CXCR6+ γδ T cells in the peripheral blood from RSA patients was lower than normal pregnancies. The expression of CXCR6 was highest in the decidual γδ T cells among decidual immune cells, and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased. Expression of granzyme B in the decidual γδ T cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16, and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidual γδ T cells. Both the expression of CXCR6 in the decidual γδ T cells and proliferation of the decidual γδ T cells were promoted by HTR8/SVneo trophoblast cells. On the other hand, decidual γδ T cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation. In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidual γδ Τ cells and trophoblasts. Conclusions: Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidual γδ Τ cells and trophoblasts, and it showed a light on the effective strategy of adoptive transfer of CXCR6+ γδ T cells on the treatment of RSA. This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.
{"title":"A defective CXCL16/CXCR6 axis increases the risk of pregnancy loss via the abnormal crosstalk between decidual γδ t cells and trophoblasts","authors":"Dengxuan Fan, Ming-qing Li, Wen-Jie Zhou, Hong-Lan Huang, Hui-Li Yang, Cong-Jian Xu","doi":"10.4103/2096-2924.324878","DOIUrl":"https://doi.org/10.4103/2096-2924.324878","url":null,"abstract":"Objective: The maternal–fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus. The interaction between decidual γδ Τ cells and trophoblasts plays a pivotal role during successful pregnancy; however, their physiological functions in early-term human pregnancy are still not completely illustrated. This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidual γδ T cells and HTR8/SVneo trophoblast cells. Methods: The percentile of CXCR6+ γδ T cells in the peripheral blood from normal female and recurrent spontaneous abortion (RSA) patients was analyzed by flow cytometry. The expression of CXCR6 was detected in decidual immune cells via flow cytometry, and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus (LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells. Expression of granzyme B and cytokines and proliferation of decidual γδ T cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry. Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay. Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss. Results: The percentile of CXCR6+ γδ T cells in the peripheral blood from RSA patients was lower than normal pregnancies. The expression of CXCR6 was highest in the decidual γδ T cells among decidual immune cells, and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased. Expression of granzyme B in the decidual γδ T cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16, and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidual γδ T cells. Both the expression of CXCR6 in the decidual γδ T cells and proliferation of the decidual γδ T cells were promoted by HTR8/SVneo trophoblast cells. On the other hand, decidual γδ T cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation. In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidual γδ Τ cells and trophoblasts. Conclusions: Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidual γδ Τ cells and trophoblasts, and it showed a light on the effective strategy of adoptive transfer of CXCR6+ γδ T cells on the treatment of RSA. This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"129 - 139"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41342035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.4103/2096-2924.322839
Ting-Feng Lu, Yunzhen Ye, Xiao-tian Li, Ying Zhang
Objective: The role of Vitamin D-binding protein (DBP) in preeclampsia (PE) pathogenesis is unknown. In this study, we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls, and aimed to explore the effect of DBP on endothelial cells (ECs) and the underlying mechanism. Methods: DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry. The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA (siRNA) and DBP-expression vector, respectively. The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC (HUVEC) cultures. Angiogenic effects on HUVECs were assessed by tube formation assays, and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer. The expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-2, as well as the phosphorylation of different residues of VEGFR-2 in HUVECs, were determined by western blotting. Results: DBP expression was significantly increased in the placental tissues collected from PE patients. The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs, in addition to their proliferation and migration. Furthermore, treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996, whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951, 996, and 1,175. Conclusions: The expression of DBP is increased in the placentas of PE patients. DBP plays potential roles in endothelial dysfunction, which contributes to PE development, by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.
{"title":"Vitamin d-binding protein is involved in the pathogenesis of preeclampsia by inhibiting the tyrosine phosphorylation of vascular endothelial growth factor receptor-2 in endothelial cells","authors":"Ting-Feng Lu, Yunzhen Ye, Xiao-tian Li, Ying Zhang","doi":"10.4103/2096-2924.322839","DOIUrl":"https://doi.org/10.4103/2096-2924.322839","url":null,"abstract":"Objective: The role of Vitamin D-binding protein (DBP) in preeclampsia (PE) pathogenesis is unknown. In this study, we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls, and aimed to explore the effect of DBP on endothelial cells (ECs) and the underlying mechanism. Methods: DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry. The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA (siRNA) and DBP-expression vector, respectively. The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC (HUVEC) cultures. Angiogenic effects on HUVECs were assessed by tube formation assays, and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer. The expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-2, as well as the phosphorylation of different residues of VEGFR-2 in HUVECs, were determined by western blotting. Results: DBP expression was significantly increased in the placental tissues collected from PE patients. The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs, in addition to their proliferation and migration. Furthermore, treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996, whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951, 996, and 1,175. Conclusions: The expression of DBP is increased in the placentas of PE patients. DBP plays potential roles in endothelial dysfunction, which contributes to PE development, by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"140 - 147"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45230532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.4103/2096-2924.324822
Wanlin Zhang, Zhe Dong, Jun Zhang, M. Lyu, Wei Zhang, Jian-Lei Huang, Xin Yang
This study aimed to estimate the risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and other side effects following the use of drospirenone (DRSP)-containing combined oral contraceptives (COCs). When compared with non-DRSP-containing COCs, DRSP-containing COCs decreased the risk of VTE by 15% in the overall study population, although this was not statistically significant (adjusted hazard ratio/risk ratio [95% confidence interval] 0.85 [0.69, 1.04]). DRSP-containing COCs also showed significant benefits in terms of ATE risk. The body mass index of the subjects significantly decreased by 0.64 kg/m2 after taking the DRSP-containing COCs for 6 months. We concluded that DRSP-containing COCs were safe for use and could be broadly recommended.
{"title":"Comparison of risks of thromboembolism of drospirenone-containing and nondrospirenone -containing combined oral contraceptive use: A meta-analysis","authors":"Wanlin Zhang, Zhe Dong, Jun Zhang, M. Lyu, Wei Zhang, Jian-Lei Huang, Xin Yang","doi":"10.4103/2096-2924.324822","DOIUrl":"https://doi.org/10.4103/2096-2924.324822","url":null,"abstract":"This study aimed to estimate the risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and other side effects following the use of drospirenone (DRSP)-containing combined oral contraceptives (COCs). When compared with non-DRSP-containing COCs, DRSP-containing COCs decreased the risk of VTE by 15% in the overall study population, although this was not statistically significant (adjusted hazard ratio/risk ratio [95% confidence interval] 0.85 [0.69, 1.04]). DRSP-containing COCs also showed significant benefits in terms of ATE risk. The body mass index of the subjects significantly decreased by 0.64 kg/m2 after taking the DRSP-containing COCs for 6 months. We concluded that DRSP-containing COCs were safe for use and could be broadly recommended.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"154 - 160"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45527044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vitro maturation (IVM) has been used in clinical settings for 30 years. The merits of IVM include that it needs a relatively small amount of hormones and short treatment period. However, because the effectiveness of IVM is lower than that of controlled ovarian hyperstimulation, there are few centers routinely use IVM, and it is only applicable to a few special populations. In this article, several oocyte sources related to IVM have been discussed and the effects of gonadotropin priming and triggering on IVM are described. Furthermore, we have reviewed the optimization of IVM culture conditions in recent years along with the effects of IVM on genes of oocytes and cumulus cells and the obstetric and neonatal outcomes. We aim to provide indications for future improvement of IVM technology so that the success rates of IVM technology in special populations can be improved. We hope that this mild and natural protocol can be applied to more populations, including individuals with normal ovulation.
{"title":"Research Progress of In vitro Oocyte Maturation","authors":"Yuan-Xue Jing, Yi-Qing Wang, Hong-Xing Li, F. Yue, Shi-Long Xue, Xuehong Zhang","doi":"10.4103/2096-2924.325827","DOIUrl":"https://doi.org/10.4103/2096-2924.325827","url":null,"abstract":"In vitro maturation (IVM) has been used in clinical settings for 30 years. The merits of IVM include that it needs a relatively small amount of hormones and short treatment period. However, because the effectiveness of IVM is lower than that of controlled ovarian hyperstimulation, there are few centers routinely use IVM, and it is only applicable to a few special populations. In this article, several oocyte sources related to IVM have been discussed and the effects of gonadotropin priming and triggering on IVM are described. Furthermore, we have reviewed the optimization of IVM culture conditions in recent years along with the effects of IVM on genes of oocytes and cumulus cells and the obstetric and neonatal outcomes. We aim to provide indications for future improvement of IVM technology so that the success rates of IVM technology in special populations can be improved. We hope that this mild and natural protocol can be applied to more populations, including individuals with normal ovulation.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"183 - 192"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47020853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As an innovative in vitro culture model, organoids have been established by cell sorting and subsequent culture in three-dimensional culture systems. Organoids can be derived from induced pluripotent stem cells or organ-restricted adult stem cells. Compared with traditional two-dimensional cell culture models and patient-derived xenograft models, organoids possess long-term genetic stability and can better retain the characteristics of source tissues or organs. These advantages have led to the increased use of ovarian and fallopian tube organoids in various fields of research, including cell differentiation and development, establishment of disease occurrence and progression models, tissue regeneration and reconstruction, individual drug screening, immune cell co-culture, and maternal–fetal medicine. This review briefly summarizes the recent progress in the application of ovarian and fallopian tube organoids in the field of obstetrics and gynecology.
{"title":"Progress in the application of ovarian and fallopian tube organoids","authors":"Yijia Dai, Jinsong Wei, Jing Xu, Ke-Rui Li, Jing Wang, Ran-Ran Cha, Yu Kang","doi":"10.4103/2096-2924.322840","DOIUrl":"https://doi.org/10.4103/2096-2924.322840","url":null,"abstract":"As an innovative in vitro culture model, organoids have been established by cell sorting and subsequent culture in three-dimensional culture systems. Organoids can be derived from induced pluripotent stem cells or organ-restricted adult stem cells. Compared with traditional two-dimensional cell culture models and patient-derived xenograft models, organoids possess long-term genetic stability and can better retain the characteristics of source tissues or organs. These advantages have led to the increased use of ovarian and fallopian tube organoids in various fields of research, including cell differentiation and development, establishment of disease occurrence and progression models, tissue regeneration and reconstruction, individual drug screening, immune cell co-culture, and maternal–fetal medicine. This review briefly summarizes the recent progress in the application of ovarian and fallopian tube organoids in the field of obstetrics and gynecology.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"174 - 182"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42756305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.4103/2096-2924.322829
Hui-Hui Shen, Zhen-zhen Lai, Hui-Li Yang, Jia-Wei Shi, Ming-qing Li
Although considerable advances have been made in the field of assisted reproductive technology (ART), millions of couples still suffer from infertility and miscarriage. In a large number of cases, the etiology of these common reproductive failures remains unknown. However, the significance of autoantibodies in infertility and miscarriage has sparked extensive interest because of their pleiotropic roles in disrupting normal pregnancy. This review discusses the pleiotropic roles of a series of autoantibodies in infertility and miscarriage. A brief recapitulation of how the autoantibodies interfere with ART outcomes and treatments for this type of idiopathic infertility or miscarriage is also provided. While several disputes remain to be resolved, further studies employing better designs and larger sample sizes are required in view of the therapeutic potential of autoantibody inhibitors and the future of contraceptive vaccines.
{"title":"Role of autoantibodies in infertility, miscarriage, and assisted reproductive technology outcomes","authors":"Hui-Hui Shen, Zhen-zhen Lai, Hui-Li Yang, Jia-Wei Shi, Ming-qing Li","doi":"10.4103/2096-2924.322829","DOIUrl":"https://doi.org/10.4103/2096-2924.322829","url":null,"abstract":"Although considerable advances have been made in the field of assisted reproductive technology (ART), millions of couples still suffer from infertility and miscarriage. In a large number of cases, the etiology of these common reproductive failures remains unknown. However, the significance of autoantibodies in infertility and miscarriage has sparked extensive interest because of their pleiotropic roles in disrupting normal pregnancy. This review discusses the pleiotropic roles of a series of autoantibodies in infertility and miscarriage. A brief recapitulation of how the autoantibodies interfere with ART outcomes and treatments for this type of idiopathic infertility or miscarriage is also provided. While several disputes remain to be resolved, further studies employing better designs and larger sample sizes are required in view of the therapeutic potential of autoantibody inhibitors and the future of contraceptive vaccines.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"161 - 173"},"PeriodicalIF":0.8,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47619001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.4103/2096-2924.320882
Zhi-Jing Tang, Haiyun Guan, Lu Wang, Wei Zhang
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 pregnancy. Decidualization abnormalities can cause female infertility and abortion, and the decidualization model in vitro is an important tool for studying relevant mechanisms. This article summarizes several in vitro decidualization models in recent research from three aspects, including the selection of model cells and culture systems, evaluation of decidualization markers, and induction schemes. These models can be appropriately selected and applied in specific endometrium-related disease models, such as endometriosis, recurrent pregnancy loss, and preeclampsia.
{"title":"Research progress on human endometrium decidualization In vitro cell models","authors":"Zhi-Jing Tang, Haiyun Guan, Lu Wang, Wei Zhang","doi":"10.4103/2096-2924.320882","DOIUrl":"https://doi.org/10.4103/2096-2924.320882","url":null,"abstract":"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 pregnancy. Decidualization abnormalities can cause female infertility and abortion, and the decidualization model in vitro is an important tool for studying relevant mechanisms. This article summarizes several in vitro decidualization models in recent research from three aspects, including the selection of model cells and culture systems, evaluation of decidualization markers, and induction schemes. These models can be appropriately selected and applied in specific endometrium-related disease models, such as endometriosis, recurrent pregnancy loss, and preeclampsia.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"119 - 127"},"PeriodicalIF":0.8,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46793400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, an increasing number of young women have been diagnosed with cancer, including some nulliparous women. Therefore, many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments. It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient. On the other hand, there has been a sharp increase in microRNAs (miRNAs) as potential biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy of several diseases. MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms. Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases. Therefore, we provide an overview of the biogenesis, function, and role of miR-543 in various systems. These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.
{"title":"MicroRNA-543 in systemic diseases and possible applications in gynecologic tumors","authors":"Yanran Sheng, Wen-Ting Hu, Chunyan Wei, Yukai Liu, Yuyin Liu, Xiaoyong Zhu","doi":"10.4103/2096-2924.320879","DOIUrl":"https://doi.org/10.4103/2096-2924.320879","url":null,"abstract":"In recent years, an increasing number of young women have been diagnosed with cancer, including some nulliparous women. Therefore, many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments. It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient. On the other hand, there has been a sharp increase in microRNAs (miRNAs) as potential biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy of several diseases. MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms. Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases. Therefore, we provide an overview of the biogenesis, function, and role of miR-543 in various systems. These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"107 - 118"},"PeriodicalIF":0.8,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48330124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.4103/2096-2924.320886
Yunqing Zhu, Xingyu Yan, Hua Li, Cong Zhang
Placentation and tumorigenesis have many common features. Human placentation builds a maternal–fetal connection, circumvents maternal immune rejection of the fetus, and utilizes mechanisms that support tumorigenesis, such as proliferation, invasion, angiogenesis, and immune tolerance. Trophoblasts of the human placenta mimic the behavior of malignant cells, proliferating and invading the uterine decidua until reaching the myometrium and remodeling the spiral arteries that establish a new vascular system and escape the maternal immune response. These processes are under precise temporal and spatial regulation, and their dysregulation is associated with different pregnancy syndromes, including preeclampsia (PE), a pregnancy syndrome that is the leading cause of maternal and perinatal mortality and morbidity. At present, the precise mechanisms underlying the development of PE remain unclear. Here, we summarize and dissect the features between physiological placentation and pathological tumorigenesis to explore the pathogenesis of PE – which we believe to be the result of insufficient placentation, compared to the overaggression of tumorigenesis – to provide novel strategies to prevent and treat PE.
{"title":"Insights into the pathogenesis of preeclampsia based on the features of placentation and tumorigenesis","authors":"Yunqing Zhu, Xingyu Yan, Hua Li, Cong Zhang","doi":"10.4103/2096-2924.320886","DOIUrl":"https://doi.org/10.4103/2096-2924.320886","url":null,"abstract":"Placentation and tumorigenesis have many common features. Human placentation builds a maternal–fetal connection, circumvents maternal immune rejection of the fetus, and utilizes mechanisms that support tumorigenesis, such as proliferation, invasion, angiogenesis, and immune tolerance. Trophoblasts of the human placenta mimic the behavior of malignant cells, proliferating and invading the uterine decidua until reaching the myometrium and remodeling the spiral arteries that establish a new vascular system and escape the maternal immune response. These processes are under precise temporal and spatial regulation, and their dysregulation is associated with different pregnancy syndromes, including preeclampsia (PE), a pregnancy syndrome that is the leading cause of maternal and perinatal mortality and morbidity. At present, the precise mechanisms underlying the development of PE remain unclear. Here, we summarize and dissect the features between physiological placentation and pathological tumorigenesis to explore the pathogenesis of PE – which we believe to be the result of insufficient placentation, compared to the overaggression of tumorigenesis – to provide novel strategies to prevent and treat PE.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"97 - 106"},"PeriodicalIF":0.8,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49415217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-01DOI: 10.4103/2096-2924.320885
Dan Sun, Hua Long, Xiao He, Weijie Kang, Juan Zhou, Jianjian Huang
Objective: Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications, such as preeclampsia. Syncytin-A (synA) has been reported to be expressed in the placenta. The contribution of synA to developmental abnormalities and dysfunction of the placenta remains elusive. In this study, we aimed to explore the role of synA in placental development and functions. Methods: SynA-knockout mice were generated using the CRISPR-Cas9 method, and the phenotypes of the placenta and fetus of synA-knockout mice were observed. Real-time quantitative polymerase chain reaction (PCR) and routine PCR were employed to detect the genotypes of the offspring. CD31 immunohistochemistry was used to evaluate the vessel density of the placenta, and the protein levels of key molecules were measured by western blotting. Results: SynA knockout caused fetal death. Furthermore, synA-knockout mice showed placental developmental abnormalities, indicated by a thinner labyrinth layer, thicker spongiotrophoblast layer, lower blood vessel density, and significantly higher numbers of apoptotic trophoblasts, when compared with wild-type littermates. Mechanistically, synA ablation induced apoptosis-inducing factor (AIF) cleavage and nuclear localization and promoted placental trophoblast apoptosis. In addition, synA knockout increased the calpain1 protein levels. The calpain1 inhibitor calpeptin blocked synA knockout-induced AIF cleavage, partially restoring the placental structural abnormalities of synA-knockout mice. Conclusions: SynA knockout leads to placental developmental abnormalities by inducing trophoblastic apoptosis via the calpain1-AIF pathway.
{"title":"Syncytin-A knockout induces placental developmental abnormalities partially through calpain1-apoptosis-inducing factor-mediated trophoblast apoptosis","authors":"Dan Sun, Hua Long, Xiao He, Weijie Kang, Juan Zhou, Jianjian Huang","doi":"10.4103/2096-2924.320885","DOIUrl":"https://doi.org/10.4103/2096-2924.320885","url":null,"abstract":"Objective: Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications, such as preeclampsia. Syncytin-A (synA) has been reported to be expressed in the placenta. The contribution of synA to developmental abnormalities and dysfunction of the placenta remains elusive. In this study, we aimed to explore the role of synA in placental development and functions. Methods: SynA-knockout mice were generated using the CRISPR-Cas9 method, and the phenotypes of the placenta and fetus of synA-knockout mice were observed. Real-time quantitative polymerase chain reaction (PCR) and routine PCR were employed to detect the genotypes of the offspring. CD31 immunohistochemistry was used to evaluate the vessel density of the placenta, and the protein levels of key molecules were measured by western blotting. Results: SynA knockout caused fetal death. Furthermore, synA-knockout mice showed placental developmental abnormalities, indicated by a thinner labyrinth layer, thicker spongiotrophoblast layer, lower blood vessel density, and significantly higher numbers of apoptotic trophoblasts, when compared with wild-type littermates. Mechanistically, synA ablation induced apoptosis-inducing factor (AIF) cleavage and nuclear localization and promoted placental trophoblast apoptosis. In addition, synA knockout increased the calpain1 protein levels. The calpain1 inhibitor calpeptin blocked synA knockout-induced AIF cleavage, partially restoring the placental structural abnormalities of synA-knockout mice. Conclusions: SynA knockout leads to placental developmental abnormalities by inducing trophoblastic apoptosis via the calpain1-AIF pathway.","PeriodicalId":20959,"journal":{"name":"Reproductive and Developmental Medicine","volume":"5 1","pages":"63 - 70"},"PeriodicalIF":0.8,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41916264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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