IL-24 Expression at Maternal-fetal Interface and Its Roles in Trophoblast Invasion

In this study, the expression of IL-24 at maternal-fetal interface and the roles in extravillous trophoblast （the TEV-1 cell line） invasion were examined. Immunohistochemistry was used to detect the expression of IL-24 in villi and decidual tissue. The proliferation of TEV-1 cells under the effect of IL-24 was measured by MTT assay. The invasiveness of TEV-1 cells under the effect of recombinant IL-24 （rhIL-24） was examined by transwell system. Immunohistochemical detection showed that IL-24 was expressed in the villi and decidual tissue, and distributed in villous column, trophoblasts, stroma and blood vessels. The proliferation of TEV-1 cells was not inhibited by rhIL-24 of various concentrations. The examination of invasion in vitro showed that rhIL-24 could inhibit the invasion of TEV-1 cells in a concentration-dependent manner. The results suggested IL-24 could inhibit the invasion of TEV-1 cells. Therefore, IL-24 produced by maternal-fetal interface in human first trimester pregnancy may influence the invasion of trophoblasts and is involved in normal pregnancy.

Maternal-Fetal Prognosis of the Prophylactic Cesaarian versus Emergency Cesaarian at the Reference Health Center of Commune V of Bamako District, Mali

Objectives: The goal was to assess the risk factors for emergency cesarean section versus prophylactic caesarean section. Materials and Methods: This was a descriptive analytical cross-sectional study of the Type Cas/Witnesses at the Reference Health Centre of Commune V of the District of Bamako in Mali. The sample consisted of 100 cases for 200 controls (1 case for 2 controls) with retrospective collection of data for the period from January 1 to July 11, 2011 (6 months and 11 days). Results: During the study period, out of a total of 3559 deliveries, we recorded 2,794 vaginal deliveries, 78.50% and 765 caesarean sections or 21.50%. Of the 765ceras, we performed 353 emergency caesarean sections or 46.15% and 412 prophylactic caesarean sections 53.85%. We have selected 100 prophylactic caesarean section files and 200 emergency caesarean section files. The average age of the patients was 27.41 years-5.84 with extreme ages of 14 to 40 years. 100% of our patients (Cas) had performed at least one antenatal consultation compared to 83.5% of the parturients evacuated (Witnesses). The most frequently cited reasons for evacuation were: acute fetal suffering, non-cephalic presentation and excessive uterine height with 30%, 17.5% and 12% respectively. The bulk of the caesarean section indications were dominated by dystocies with 90% in cases compared to 65% in Witnesses, followed by acute fetal suffering with 30% in Witnesses. We recorded 30% perinatal deaths among Witnesses compared to 1% in Cases. We recorded 16 uterine ruptures in the Witnesses among which 2 hysterectomies and 14 hystererraphia. Conclusion: Prophylactic caesarean section improves maternal and perinatal prognosis more than emergency caesarean section.

Uropathogens of Urinary Tract Infection in Pregnancy and Maternal-Fetal Outcomes at the Douala Referral Hospital, Cameroon: A Case-Control Study

Background: Urinary tract infection (UTI) is common in pregnancy and accounts for a high burden of maternal and perinatal morbidity/mortality and health expenditure. The burden of this condition has been understudied in Cameroon. We aimed to determine the uropathogens of urinary tract infection in pregnancy, and the maternal-fetal outcomes of UTI at the Douala Referral Hospital. Methods: We conducted an analytic matched case-control study of 206 pregnant women with evidence of urinary tract infection (103 cases) and those without (103 controls) who underwent antenatal care and gave birth at the DRH from January 2019 to April 2019. Socio-demographic, laboratory and maternal-fetal outcome data were collected using a pre-tested structured questionnaire and analyzed with SPSS version 23. Statistical significance was set at p < 0.05. Results: Escherichia coli (51.5%), Proteus mirabilis (15.5%), Staphylococcus aureus (11.7%) and Klebsiella sp. (6.8%) were the predominant uropathogens of UTI. Maternal outcomes of UTI were puerperal pyelonephritis (AOR 3.1;95% CI: 1.11 - 3.55, p = 0.0023), preterm labor (AOR 4.4;95% CI: 1.0 - 2.7, p = 0.008) and preterm birth (AOR 4.6;95% CI 1.9 - 22.9, p = 0.05). Furthermore, low birth weight (AOR 2.1;95% CI: 0.8 - 5.6, p = 0.05), neonatal infection (AOR 13;95% CI: 0.9 - 191.6, p = 0.04) and neonatal intensive care unit admission (AOR 2.5;95% CI: 1.7 - 3.6, p = 0.003) were fetal outcomes of UTI. Conclusion: Escherichia coli was the main uropathogenic agent of UTI during pregnancy. Maternal outcomes of UTI were puerperal pyelonephritis, preterm labor and delivery while fetal outcomes include: low-birth weight, neonatal infection and neonatal intensive care admission. Prompt diagnosis of this condition is the cornerstone to avoid adverse outcomes.

Research Progress of the Maternal-Fetal Interface Immune Microenvironment Regulated by Traditional Chinese Medicine in the Treatment of Recurrent Spontaneous Abortion

This article is a summary of the research progress of the maternal-fetal interface immune microenvironment regulated by traditional Chinese medicine in the treatment of recurrent spontaneous abortion.The imbalance of the immune microenvironment at the maternal-fetal interface is closely related to the occurrence of recurrent spontaneous abortion.Traditional Chinese medicine can maintain the homeostasis of the immune microenvironment at the maternal-fetal interface by regulating the function of immune cells and the expression of related cytokines.

Proangiogenic Macrophage Development in Human Prenatal Stage:A Key Element in Maternal-Fetal Medicine Puzzle

Introduction Macrophages,a major immune cell type constituting the human innate immune system,are involved in various physiological processes,such as tissue development,remodeling,homeostasis,and repair,crucial for maintaining normal growth and development of embryos/fetuses.1-3 Influenced by their cellular origin and specific tissue environments,macrophages exhibit a diverse range of phenotypes.

Single-cell sequencing analysis of the maternal-fetal interface

The microenvironment at the maternal-fetal interface is optimized to facilitate the development and survival of the fetus during pregnancy.It involves a balance between cell populations and interactions of the fetal placenta with various cell types(ie,stromal cells,endothelial cells,immune cells,and fibroblasts)that are embedded in the maternal endometrium/decidua.Aberrant shifts in cell populations and deranged cell-cell interactions are closely related to pregnancy disorders.Thus,analysis of the dynamic changes in cell populations and their interactions at the maternal-fetal interface in normal and complicated pregnancies is essential to provide insights into the fundamental processes involved in the establishment and maintenance of normal pregnancy,and how these processes are dysregulated.Thus,informing novel pathways for therapeutic targets of pregnancy complications.Single-cell sequencing(SCS)is a powerful tool for transcriptome analysis at single-cell resolution.Combined with information on the developmental trajectory and function of different cell populations,SCS can provide an unparalleled opportunity for refining the spatiotemporal cell atlas to elaborate dynamic changes in cell populations and their interactions in tissues that consist of highly heterogeneous cell populations such as the maternal-fetal interface.This minireview briefly summarizes traditional methods and their limitations for analyzing maternal-fetal interface cell-cell interactions,and introduces the current applications,advantages,limitations,and prospective applications of SCS in research on maternal-fetal interactions.

Mechanisms of Traditional Chinese Medicine Bushenantai granules(补肾安胎颗粒) in promoting angiogenesis at the maternal-fetal interface of recurrent spontaneous abortion mice

OBJECTIVE:To assess the effects of Bushenantai(BSAT)granule(补肾安胎颗粒)on angiogenesis-related factors[E2,P,and vascular endothelial growth factor(VEGF)]at the maternal-fetal interface of recurrent spontaneous abortion(RSA)mice,and to evaluate the role of BSAT in promoting angiogenesis at the maternal-fetal interface by influencing the expression of sex hormones,and VEGF.METHODS:A mouse model with normal pregnancy and another with Clark’s classic RSA were established.The RSA mice were randomly assigned to six groups:normal,model,progesterone,high-doseBSAT granule(BSAT-H),medium-dose-BSAT granule(BSAT-M),and low-dose-BSAT granule(BSAT-L)(n=10 for each group).The embryo loss rate and the histopathological changes in the decidual tissues were measured.Serum levels of estrogen(E2),progesterone(P),and VEGF were detected by enzyme-linked immunosorbent assay.The m RNA and protein expressions of estradiol receptor(ER),progesterone receptor(PR),VEGF,and vascular endothelial growth factor receptor 2(VEGFR2)in the decidual tissues were identified by immunohistochemistry,Western blotting,and quantitative reverse transcription polymerase chain reaction.RESULTS:The embryo loss rate in all groups that received BSAT treatment was reduced,while the number of blood vessels at decidual tissues was increased.The serum levels of E2,P and VEGF were elevated,and the m RNA and protein expressions of ER,PR,VEGF,and VEGFR2 in the decidual tissues were enhanced.CONCLUSION:BSAT can improve angiogenesis at the maternal-fetal interface and reduce the embryo loss rate,which may be associated with its ability to increase the serum levels of estrogen,progesterone,and VEGF,in addition to up-regulation of m RNA and protein expression of ER,PR,VEGF,and VEGFR2 in the decidual tissues.

Single-Cell RNA Expression Profiling of ACE2 and AXL in the Human Maternal-Fetal Interface

2019 novel coronavirus disease has resulted in thousands of critically ill patients in China,which is a serious threat to people’s life and health.Severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)was reported to share the same receptor,angiotensin-converting enzyme 2(ACE2),with SARS-CoV.Here,based on the public single-cell RNA-sequencing database,we analyzed the mRNA expression profile of putative receptor ACE2 and AXL receptor tyrosine kinase(AXL)in the early maternal-fetal interface.The result indicates that the ACE2 has very low expression in the different cell types of early maternal-fetal interface,except slightly high in decidual perivascular cells cluster 1(PV1).Interestingly,we found that the Zika virus(ZIKV)receptor AXL expression is concentrated in perivascular cells and stromal cells,indicating that there are relatively more AXL-expressing cells in the early maternal-fetal interface.This study provides a possible infection route and mechanism for the SARS-CoV-2-or ZIKV-infected mother-to-fetus transmission disease,which could be informative for future therapeutic strategy development.

Toll-Like Receptor-Dependent Antiviral Responses at the Maternal-Fetal Interface

The maternal-fetal interface is a key barrier to protect the fetus from infection.Toll-like receptors (TLRs) at the maternal-fetal interface are involved in antiviral responses.TLRs are expressed in both maternal decidua and fetal trophoblasts.Virus-induced activation of TLR signaling pathways triggers the release of interferon-related antiviral molecules and other inflammatory cytokines and/or chemokines by the host innate immune system,which may disrupt immune tolerance at the maternal-fetal interface and lead to pregnancy complications.In this review,we summarize the state of knowledge on the most common viral infections during pregnancy,antiviral TLR responses at the maternal-fetal interface,and TLR-associated pregnancy complications.

Role of Decidual Natural Killer Cells at the Maternal-Fetal Interface during Pregnancy

Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation.Decidual natural killer(NK)cells account for 50%-70% of decidual immune cells in early pregnancy,suggesting that they play important roles in various events,such as embryo implantation and vascular remodeling.Many studies have shown that decidual NK cells interact with other cells either through direct contact or the secretion factors such as cytokines and chemokines.Hence,this review aimed to present the phenotypic characteristics,classification,and functions of decidual NK cells at the maternal-fetal interface during pregnancy.

The role of extracellular matrix on unfavorable maternal-fetal interface:focusing on the function of collagen in human fertility

Extracellular matrix(ECM)is characterized as widespread,abundant,and pluripotent.Among ECM members,collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions,which has been extensively used in tissue engineering.Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal-fetal interface including menstrual cycling,decidualization,embryo implantation and pregnancy maintenance.Moreover,disorders in these events may eventually lead to failure of pregnancy.Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples,some unfavorable outcomes,such as recurrent implantation failure(RIF),recurrent pregnancy loss(RPL)or recurrent miscarriage(RM),keep troubling the clinicians and patients.Recently,in vitro three-dimensional(3D)model mimicking the microenvironment of the maternal-fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy.The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus.Focusing on collagen,the present review summarized the degradation and regulation of ECM and its role in normal menstruation,endometrium receptivity and unsatisfying events occurring in infertility treatments,as well as the application in therapeutic approaches to improve pregnancy outcomes.More investigations about ECM focusing on the maternal-fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments.

Ethically Justified,Practical Guidance for the Professionally Responsible Investigation of Maternal-Fetal Intervention for Fetal or Neonatal Benefit

This paper provides ethical guidance for the professionally responsible clinical investigation of maternal-fetal investigation for fetal or neonatal benefit and its transition into clinical practice.We present an ethical framework based on the ethical principles of beneficence,respect for autonomy,and justice,the professional virtue of integrity,and the ethical concept of the fetus as a patient.We identify the implications of this ethical framework for the qualifications that centers for maternal-fetal intervention should satisfy.These centers have the ethical obligation to provide prospective review and oversight of both innovation(an experiment undertaken to benefit an individual patient)and research(an experiment undertaken to create generalizable knowledge).We describe ethically justified criteria for innovation and early-phase research,for randomized clinical trials,and for the responsible transition into clinical practice.We also identify the elements of the informed consent process,including measures to prevent therapeutic misconception by pregnant patients during the informed consent process.The scientific,clinical,and ethical requirements of maternal-fetal investigation are demanding.However,the commitment to safety and quality requires that they be met.Fulfilling this commitment will result in well-documented professionally responsible investigation of maternal-fetal intervention for fetal and neonatal benefit.

Frontier Progress in the Establishment of Trophoblast Stem Cell and the Identification of New Cell Subtypes at the Maternal-Fetal Interface

Proper development of the human placenta is of vital importance for a successful pregnancy,and a series of pregnancy complications are considered originating from dysfunctional placentas.Like other organ system development,placentation requires large numbers of co-regulators,while the underlying molecular mechanisms orchestrating the placental formation and function are poorly understood.Although we have made many signs of progress in understanding the placental architectures and developments using mouse models,the species-specific differences impede our progress due to the lack of appropriate model systems.In the past few years,major progress has been made by the establishment of novel in-vitro self-renewing stem cell models,as well as identifying the full picture of the cellular organization of the maternal and fetal interface.Providing the tools for the investigation of placentation and reproductive-related regulation mechanism.In this review,we focus on the detailed progress of the human trophoblast stem cells culturing system,and the cellular and molecular terrain at the maternal-fetal interface,respectively,thus providing new insights into placental development.

MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss

Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.

Tailored nutritional interventions: A precision approach to managing gestational diabetes mellitus

Gestational diabetes mellitus(GDM)is a risk to maternal-fetal health due to uncertain diagnostic criteria and treatment options.Luo's study demonstrated the efficacy of customized nutritional therapies in controlling GDM.Tailored strategies led to significant body weight loss,improved glucolipid metabolism,and fewer prenatal and newborn problems.This holistic approach,which emphasizes the notion of’chrononutrition’,takes into account optimal meal timing that is in sync with circadian rhythms,as well as enhanced sleep hygiene.Implementing tailored dietary therapy,managing meal timing,and ensuring appropriate sleep may improve results for women with GDM,opening up a possible avenue for multi-center trials.

Gestational diabetes mellitus:The optimal time of delivery

Gestational diabetes mellitus(GDM)is a common pregnancy complication strongly associated with poor maternal-fetal outcomes.Its incidence and prevalence have been increasing in recent years.Women with GDM typically give birth through either vaginal delivery or cesarean section,and the maternal-fetal outcomes are related to several factors such as cervical level,fetal lung maturity,the level of glycemic control still present,and the mode of treatment for the condition.We categorized women with GDM based on the latter two factors.GDM that is managed without medication when it is responsive to nutrition-and exercise-based therapy is considered diet-and exercise-controlled GDM,or class A1 GDM,and GDM managed with medication to achieve adequate glycemic control is considered class A2 GDM.The remaining cases in which neither medical nor nutritional treatment can control glucose levels or patients who do not control their blood sugar are categorized as class A3 GDM.We investigated the optimal time of delivery for women with GDM according to the classification of the condition.This review aimed to address the benefits and harms of giving birth at different weeks of gestation for women with different classes of GDM and attempted to provide an analytical framework and clearer advice on the optimal time for labor.

Sanitary Evacuations at the Maternity Unit of the Social Hygiene Institute (IHS) in Dakar in 2020

Objective: Determine the frequency of evacuations, specify the epidemiological and clinical characteristics of the evacuees, evaluate the data of the evacuation, the management and the maternal-fetal prognosis. Methods: Prospective and descriptive retrospective study concerning obstetrical evacuations received at the maternity ward of the Hospital of the Institute of Social Hygiene in Dakar between January 1 and December 31, 2020, i.e. a period of 12 months. Results: During the study period, we collected 1156 evacuees out of a total of 3507 patients treated in the Service, i.e. a frequency of 33%. The average age of the patients was 27.07 years with extremes of 14 and 46 years. Patients aged between 20 and 29 were the most represented (51.73%). The average parity was 1.6 with extremes of 0 and 10 pares. The nulliparous (46.37%) were the majority. The majority of evacuated patients (99.6%) resided in the Dakar region, including 58% in the suburbs and 42% in the city center. The patients received had performed an average of 3 prenatal consultations with extremes ranging from 0 to 9 CPN. They most often came from health centers (55.05%) or hospitals (29.09%). The reasons for evacuations were dominated by dystocia (21.54%) followed by premature rupture of membranes (17.21%) and premature deliveries (16.35%). On admission, only 176 patients (15.2%) had an evacuation sheet. Patients transited on average through two health structures (extremes ranging from 0 to 7 structures) before reaching the reception structure. The evacuation was most often done with a private vehicle on the patient’s own means (91.96%). The outcome of the evacuees was most often vaginal delivery or hospitalization (72.79%). The majority of patients (99.4%) had evolved favorably but we deplore one maternal death (0.09%) linked to a late puerperal infection. We recorded 74 perinatal deaths and 1041 live births, i.e. a stillbirth rate of 71.1‰ live births. The causes of death were dominated by prematurity (24.7%). Conclusion: Obstetrical evacuations are frequent in our practice but they should be better organized to improve the maternal-fetal prognosis.

Relationship between expression of COX-2,TNF-α,IL-6 and autoimmune-type recurrent miscarriage

Objective:To investigate the roles of COX-2,TNF-α,IL-6 in the pathogenesis of autoimmunetype recurrent spontaneous abortion(RSA).Methods:RT-PCR was used to detect the mRNA of COX-2,TNF-α.IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The COX-2,TNF-α.IL-6 protein expressions were determined by using immunohistochemisry staining method.The COX-2,TNF-α,IL-6 protein expressions were determined by ELISA.Results:The embryo loss rates in experiment group was significantly higher than that in normal pregnancy control group,the expression of COX-2,TNF-α,IL-6 in the trophoblast cells of murine RSA and normal pregnant models.The expression of COX-2 in autoimmunetype recurrent spontaneous abortion was significantly lesser than in normal pregnant models.The expression of TNF-α,IL-6 in autoimmune-type recurrent spontaneous abortion was significantly higher than in normal pregnant models.There was a positively correlation between TNF-αand IL-6.There was no relationship between COX-2,TNF-αand IL-6.Conclusions:The abnormal expression of COX-2,TNF-αand IL-6 may result in RSA.

转铁蛋白受体在母婴间铁代谢中调节作用的研究(摘要)

缺铁性贫血(IDA)在人群中,特别是在婴幼儿及孕妇中患病率高,危害严重。虽然人们已观察到经过胎盘母婴间可发生铁的单向式逆浓度梯度转运,但对于孕妇缺铁是否影响胎儿铁供给尚有争论。我室通过对IDA患者和妊娠状态时孕妇骨髓幼红细胞(BME),胎盘滋养层合体细胞(PS)及胎肝幼红细胞(FLE)

Walking for health during pregnancy:A literature review and considerations for future research

Walking is the most commonly chosen type of physical activity(PA)during pregnancy and provides several health benefits to both mother and child.National initiatives have promoted the importance of walking in general,but little emphasis is directed toward pregnant women,the majority of whom are insufficiently active.Pregnant women face a variety of dynamic barriers to a physically active lifestyle,some of which are more commonly experienced during specific times throughout the pregnancy experience.Walking is unique in that it appears resistant to a number of these barriers that limit other types of PA participation,and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are unavailable.Preliminary intervention work suggests that walking programs can be effectively adopted into a typical pregnancy lifestyle.However,a great deal of work remains to administer successful pregnancy walking interventions,including developing and using validated methods of PA and walking assessment.This narrative review discusses the unique advantages of walking during pregnancy,provides recommendations for future intervention work,and outlines the need for pregnancy-focused community walking initiatives.Standard search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review.