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.

Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy

Normal pregnancy is a contradictory and complicated physiological process.Although the fetus carries the human leukocyte antigen(HLA)inherited from the paternal line,it does not cause maternal immune rejection.As the only exception to immunological principles,maternal-fetal immune tolerance has been a reproductive immunology focus.In early pregnancy,fetal extravillous trophoblast cells(EVTs)invade decidual tissues and come into direct contact with maternal decidual immune cells(DICs)and decidual stromal cells(DSCs)to establish a sophisticated maternal-fetal crosstalk.This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk.Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion,pre-eclampsia,and premature birth.

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.

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.

To treat or not to treat the "immunotolerant phase" of hepatitis B infection:A tunnel of controversy

Hepatitis B virus(HBV) infection is a global public health problem,with an estimated 350 million people worldwide chronically infected and approximately 500000 who die annually from HBV-related liver diseases.Management of chronic HBV is challenging and waves of guidelines emerge every year.One of the hottest topics and a matter of debate is the management of patients in their early immunotolerant phase of infection.With the lack of evidence,dealing with this particular subset of patients creates a great conflict with opposing views.In this review,the author highlights the pros and cons of these views and proposes a reasonable solution to resolve this dilemma.

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.

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.

骨髓间充质干细胞对异体T细胞几种细胞因子分泌的影响

目的:探讨骨髓间充质干细胞(MSC)对异体T淋巴细胞分泌IL-2、IL-4、IL-10、IFN-γ的影响,从而进一步探讨MSC诱导免疫耐受的机制。方法:将培养了3代后的MSC经照射后作为基底层细胞,接种分离的异体T淋巴细胞。共培养7天后,用ELASA方法检测上清中的上述四种细胞因子的蛋白含量,同时计数T淋巴细胞数量的变化,应用流式细胞仪检测与MSC共孵育前后T淋巴细胞CD3、CD4、CD8、CD25的变化。结果:(1)ELASA检测IFN-γ分泌量为667·07±14·76pg/ml;IL-10为46·19±1·41pg/ml;IL-2为33·01±5·92pg/ml;IL-4为0·15pg/ml。(2)共孵育组T淋巴细胞在数量上明显减少。(3)CD8+细胞数增多,CD25+细胞减少。结论:骨髓MSC在体外与异体T淋巴细胞共孵育后IFN-γ高分泌,可能与共孵育后T淋巴细胞亚群的改变有关。这一研究结果为预防HLA不相合的骨髓移植的GVHD的发生提供了一条新的思路。

致敏小鼠树突状细胞和T细胞Notch配体/受体的表达及大剂量过敏原的影响

目的探讨致敏小鼠Notch信号表达缺陷及大剂量过敏原对其影响。方法RT-PCR法分别检测致敏及正常小鼠树突状细胞Notch配体及T细胞Notch受体的mRNA表达情况,并观察大剂量过敏原作用对其表达的影响。结果(1)致敏小鼠树突状细胞Notch配体Jagged1,Jagged2和Delta1的mRNA表达均显著低于正常小鼠,致敏小鼠T细胞Notch1和Notch3的mRNA表达也显著低于正常小鼠(P<0.05)。(2)10mg/ml的OVA作用下,Jagged1和Notch3的mRNA表达水平较对照组显著升高(P<0.05)。结论致敏小鼠Notch信号表达缺陷,大剂量过敏原(10mg/ml的OVA)可上调Jagged1和Notch3表达。

胎盘发生过程中的细胞凋亡

细胞凋亡是一种正常的生理现象。在胚泡着床过程中 ,伴随有大量细胞凋亡。研究表明 ,胎盘发生过程中的细胞凋亡 ,对调控子宫内膜基质细胞的蜕膜化和滋养层细胞的浸润以形成胎盘具有重要意义 ;另外 ,由Fas/FasL系统介导的细胞凋亡可能与母体对胎儿的免疫耐受性有关。本文主要评述细胞凋亡的一般通路以及胎盘发生过程中细胞凋亡的调控。

早期妊娠的免疫耐受机制

胚胎对于母体来说是半异己的移植物 ,其表达部分父系抗原。孕早期母体免疫系统 ,尤其是子宫内膜局部的 NK细胞、巨噬细胞、TCR( γ+ δ+ ) T细胞和 B淋巴细胞等免疫细胞能否识别并耐受胚胎抗原 ,直接影响妊娠结局。近年来的研究表明 ,母体免疫系统在受到体内高浓度性激素水平抑制的基础上 ,通过子宫内膜局部 EAIF、HLA-G等分子产生免疫抑制 ;R80 K、BP和 PIBF等封闭因子产生免疫封闭 ;Fas L和 RCAS1诱导免疫清除 ;降调 CD1、CD80、CD86及增强 IL-1 0表达以诱导克隆无能和 /或非特异性的免疫调节等机制共同作用 ,产生对胚胎抗原的免疫耐受 ,而且这些因素之间存在相互作用 ,其中一种机制失调即引致母体对胚胎的免疫排斥 。

丁酸钠诱导的未成熟树突状细胞的免疫学功能研究

目的:探讨丁酸钠对人外周血来源的树突状细胞(DC)的成熟状态和免疫学功能的影响。方法:通过粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素4(IL-4)结合丁酸钠体外诱导人外周血来源的DC,6d后结合不同成熟因子诱导成熟,并以流式细胞仪、FITC标记的Dextran的内吞检测、混合淋巴细胞反应(MLR)、ELISA法分别检测DC的表面标志、内吞能力、DC刺激淋巴细胞增殖能力和白细胞介素12(IL-12)分泌量的改变。结果:丁酸钠可以抑制DC成熟,使DC具有较强的抗原吞噬能力,而刺激淋巴细胞增殖能力和IL-12的分泌能力下降。结论:丁酸钠可以抑制DC成熟,诱导不成熟DC生成,在移植免疫耐受方面具有较好的应用前景。

大剂量过敏原诱导哮喘小鼠T细胞不反应性及机制研究

目的探讨大剂量过敏原诱导哮喘小鼠T细胞不反应性及其机制。方法采用不同浓度的过敏原在体外处理哮喘小鼠DC及T细胞,ELISA法检测DC分泌IL-10和TGF-β1以及T细胞Th1/Th2细胞因子的分泌,并分析其相关性。结果①在0-10 mg/mL范围内,哮喘小鼠DC分泌IL-10、TGF-β1水平随处理浓度增高而增高,正常小鼠DC各浓度处理组之间无显著差异。②在0-1 mg/mL范围内,Th2细胞因子的分泌随处理浓度增高而增高,但在10 mg/mL的OVA作用的下,IL-4、IL-5等细胞因子的分泌水平则较其他组明显降低（P〈0.05）。IL-2和IFN-γ的分泌也受到明显抑制（P〈0.05）。而对正常小鼠T细胞,OVA质量浓度的变化对其Th1/Th2细胞因子的分泌无影响。③Th1/Th2细胞因子水平与DC分泌的IL-10和TGF-β1水平无明显相关性。结论大剂量过敏原（10 mg/mL的OVA）可诱导哮喘小鼠T细胞不反应性,但与DC分泌IL-10和TGF-β1水平无明显关系。

妊娠早期小鼠子宫巨噬细胞分布和活性的变化

目的:通过研究妊娠早期子宫CD14+巨噬细胞数量、分布及酸性磷酸酶(ACP)活性变化,探讨巨噬细胞与母胎免疫耐受的关系。方法:用免疫组织化学方法和酶细胞化学研究小鼠妊娠早期子宫CD14+巨噬细胞及ACP的变化。结果:对照组CD14+巨噬细胞主要分布在子宫内膜。小鼠妊娠后内膜中数目减少,第3日最少;肌膜和外膜巨噬细胞增加,第2日达到高峰。CD14免疫反应阳性面积变化趋势与此类似。第3～5日期间ACP的活性下降并维持在较低的水平。结论:巨噬细胞在着床期抗原识别和处理能力受到了抑制,参与了妊娠早期母胎免疫耐受的形成。

胸腺内注射异基因抗原诱导免疫耐受的实验研究

目的 :探讨胸腺内注射异基因抗原在建立特异性移植免疫耐受中的作用。方法 :自供体C5 7BL 6小鼠脾细胞中提取的H 2抗原 ,注入受体Balb c小鼠胸腺内 ,1w后移植供体C5 7BL 6小鼠皮肤及无关供体C3H小鼠皮肤。观察皮肤存活时间 ,同时做单向混合淋巴细胞培养 (mixedlymphocyteculture,MLC)、细胞介导的淋巴细胞毒 (cellmediatelymphocytotoxic ,CML)、迟发型超敏反应 (delayedtapehypersensitivity ,DTH)的检测。结果 :实验组移植皮肤平均存活时间 (mediansurvivaltimes,MST) >70d ,对照组MST为 12 .6± 1.6 9d ,移植C3H皮肤的无关供体组MST为 13.4± 1.42d。耐受小鼠淋巴细胞对供体淋巴细胞刺激的反应性减弱 ,而对无关供体淋巴细胞的刺激呈正常反应 ,耐受小鼠对供体靶细胞的CML作用、DTH反应特异性降低。显示出胸腺内注射抗原诱导耐受的特异性。结论 :胸腺注射异基因H