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Inhibition of Wnt activity improves peri-implantation development of somatic cell nuclear transfer embryos

National Science Review 2023年第9期10卷 163-179页

作者： Yanhe Li Caihong Zheng Yingdong Liu Jincan He Qiang Zhang Yalin Zhang Xiaochen Kou Yanhong Zhao Kuisheng Liu Dandan Bai Yanping Jia Xiaoxiao Han Yifan Sheng Jiqing Yin Hong Wang Shuai Gao Wenqiang Liu Shaorong Gao Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Signaling and Disease Research Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and Technology Tongji University CAS key laboratory of Genomic and Precision medicine Beijing Institute of Genomics Chinese Academy of Sciences and China National Center for Bioinformation key laboratory of Animal Genetics Breeding and Reproduction of the MARA National Engineering Laboratory for Animal Breeding College of Animal Science and Technology China Agricultural University

Somatic cell nuclear transfer(SCNT) can reprogram differentiated somatic cells into totipotency.Although pre-implantation development of SCNT embryos has greatly improved,most SCNT blastocysts are still arrested at the peri-implantation stage,and the underlying mechanism remains elusive.Here,we develop a 3D in vitro culture system for SCNT peri-implantation embryos and discover that persistent Wnt signals block the naive-to-primed pluripotency transition of epiblasts with aberrant H3K27me3 occupancy,which in turn leads to defects in epiblast transformation events and subsequent implantation failure.Strikingly,manipulating Wnt signals can attenuate the pluripotency transition and H3K27me3 deposition defects in epiblasts and achieve up to a 9-fold increase in cloning efficiency.Finally,single-cell RNA-seq analysis reveals that Wnt inhibition marke dly enhances the lineage developmental trajectories of SCNT blastocysts during peri-implantation development.Overall,these findings reveal diminished potentials of SCNT blastocysts for lineage specification and validate a critical peri-implantation barrier for SCNT embryos.

关键词： SCNT reprogramming implantation Wnt naïve pluripotency primed pluripotency epiblast single-cell RNA-seq epigenetic barrier

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Genetics Etiologies Associated with fetal Growth Restriction

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maternal-fetal medicine 2022年第3期4卷 206-209页

作者： Dayuan Shi Luyao Cai Luming Sun Shanghai Key Laboratory of Maternal Fetal Medicine Department of Fetal Medicine&Prenatal Diagnosis CenterShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China.

fetal growth restriction(FGR)is associated with multiple adverse perinatal outcomes,such as increased risk of intrauterine death,neonatal morbidity and mortality,and long-term adverse outcomes.Genetic etiological factors are critical in fetuses with intrauterine growth restriction,including chromosomal abnormalities,copy number variants,single gene disorders,uniparental disomy,epigenetic changes,and confined placental mosaicism.This paper aims to provide an overview of genetic defects related to FGR and to highlight the importance of prenatal genetic counseling and testing for precise diagnosis and management of FGR.

关键词： Genetics fetal growth restriction Etiology

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Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis

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Asian Journal of Andrology 2023年第3期25卷 375-381页

作者： Li Li Min-Yan Wang Hua-Bo Jiang Chun-Rong Guo Xian-Dan Zhu Xia-Qin Yao Wei-Wei Zeng Yuan Zhao Ling-Kan Chi Reproductive medicine Center Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pathology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Maternal Fetal Medicine Department of Fetal Medicine and Prenatal Diagnosis CenterShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201203China Teaching Experimental Center Shanghai University of Traditional Chinese MedicineShanghai 201203China laboratory Animal Center Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Obstetrics Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201203China Department of Gynecology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability.By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research(ICR)mouse model,we found that a ferroptosis phenomenon may exist.Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days.Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde.Epididymal sperm was also collected for semen analysis,and testicular tissue was collected for ferritin content determination,electron microscope observation of mitochondrial morphology,immunohistochemistry,real-time quantitative polymerase chain reaction,and western blot analysis.Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage,iron accumulation,and mitochondrial damage in the testes of mice.In addition,bisphenol A was confirmed to affect the expression of the ferroptosis-related genes,glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),cyclooxygenase 2(COX2),and acyl-CoA synthetase 4(ACSL4)in mouse testicular tissues.Accordingly,we speculate that bisphenol A induces oxidative stress,which leads to the ferroptosis of testicular cells.Overall,the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

关键词： bisphenol A ferroptosis mitochondrial damage oxidative stress testicular toxicity

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Low-dose aspirin in the prevention of pre-eclampsia in China: postpartum hemorrhage in subgroups of women according to their characteristics and potential bleeding risk

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Chinese Medical Journal 2023年第5期136卷 550-555页

作者： Jiahui Chen Jing Huai Li Lin Boya Li Yuchun Zhu Huixia Yang Department of Obstetrics and Gynecology Peking University First HospitalBeijing 100034China Beijing key laboratory of maternal fetal medicine of Gestational Diabetes Mellitus Beijing 100034China.

Background:The APPEC study is a large-population randomized controlled trial in China evaluating the role of low-dose aspirin prophylactic treatment for pre-eclampsia.There was no statistically significant difference in postpartum hemorrhage(PPH)incidence between the aspirin and control groups.This study aimed to evaluate the potential bleeding risk of 100 mg aspirin in high-risk pregnant women and the difference in the incidence of PPH according to maternal characteristics.Methods:This is a secondary data analysis of the APPEC study.Platelet counts and coagulation test results were collected at five follow-up visits.Subgroups defined by maternal age(<35 years and≥35 years),pre-pregnancy body mass index(pre-BMI,<28 kg/m 2 and≥28 kg/m 2),parity,gestational age at enrollment,and medical history,including pre-eclampsia,chronic hypertension,and diabetes mellitus,were analyzed.Logistic regression analysis was used to determine the statistical significance of the difference in the incidence of PPH after aspirin administration in pregnant women in each subgroup.Adjustment using multiple logistic regression models followed these analyses.Binary logistic regression was used to determine the relationship between pre-BMI and PPH.Results:There was no significant difference between the aspirin and control groups in bleeding risk(3.4%[16/464]vs.3.0%[13/434],T=0.147,P=0.701).No significant difference was found in the incidence of PPH in total(relative risk=1.220,95%confidence interval[CI]=0.720–2.067,P=0.459;aspirin group vs.control group,6.5%[30/464]vs.5.3%[23/434],P=0.459)or in subgroup analysis.A significant correlation between pre-BMI and PPH was found in the aspirin group,while in the control group there was no significant correlation(aspirin group,odds ratio[OR]=1.086,95%CI=1.004–1.175,P=0.040;control group,OR=1.060,95%CI=0.968–1.161,P=0.209).Conclusions:A dosage of 100 mg of aspirin per day,initiated from 12 to 20 gestational weeks until 34 weeks of gestation,did not increase the risk of potential bleeding and PPH regard

关键词： APPEC study Aspirin Postpartum hemorrhage Body mass index Pre-eclampsia

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Effect of SARS-CoV-2 infection in early pregnancy on placental development

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Science China(Life Sciences) 2024年第3期67卷 622-625页

作者： Shanru Yi Liping Wang Mengting Wang Wei Hong Ben Xu Xiaoying He Mengtian Yang Zhiping Wu Beiying Wang Guang Yang Shijun Shen Xinyu Cui Ruixue Wang Kai Wang Hong Wang Xiaocui Li Shaorong Gao Cizhong Jiang Jiayu Chen Clinical and Translation Research Center of shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China key laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ... 详细信息

关键词： pregnancy fetal Effect

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Exercise intervention during pregnancy induces DNA methylation alterations in maternal blood and cord blood

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Chinese Medical Journal 2023年第13期136卷 1624-1626页

作者： Jie Yan Chen Wang Yumei Wei Huixia Yang Department of Obstetrics and Gynecology Peking University First HospitalBeijing 100034China Beijing key laboratory of maternal fetal medicine of Gestational Diabetes Mellitus Beijing 100034China

To the Editor:Obesity characterized with excess accumulation of white adipose tissue increases the prevalence of gestational diabetes mellitus(GDM).Exposure to intrauterine hyperglycemia increases the long-term sequelae including cardiovascular abnormalities and metabolic syndrome in adult offspring.[1]As early as two decades ago,Dr.David Barker provided evidence that nutritional exposures in utero has a lasting impact on offspring’s health status in adulthood.[2]This emphasizes the critical role of early intrauterine environmental exposures and highlights the potential origins of adult metabolic diseases.

关键词： alterations cardiovascular pregnancy

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maternal circulating biomarkers associated with placenta accreta spectrum disorders

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Chinese Medical Journal 2023年第8期136卷 995-997页

作者： Zhirong Guo Huixia Yang Jingmei Ma Department of Obstetrics and Gynecology Peking University First HospitalBeijing 100034China Beijing key laboratory of maternal fetal medicine of Gestational Diabetes Mellitus Beijing 100034China

To the Editor:Placenta accreta spectrum(PAS)disorders refer to a spectrum of abnormal placentation.PAS subtypes include placenta accreta(creta or adherenta,PA),placenta increta(PI),and placenta percreta(PP).The incidence of PAS has dramatically increased over the past four decades.A study using a nationally representative sample in the United States showed that the prevalence of PAS was 0.29%among women who underwent cesarean delivery with live birth.[1]Women with PAS are at a considerably higher risk of concurrent hemorrhage,bladder and urinary tract injury,and hysterectomy during delivery.[1]

关键词： bladder disorders spectrum

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IDDoR:a novel reporter mouse system for simultaneous and quantitative in vivo analysis of both DNA double-strand break repair pathways

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Protein & Cell 2023年第5期14卷 369-375页

作者： Yu Chen Zhen Cui Zhixi Chen Ying Jiang Zhiyong Mao Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Tsingtao Advanced Research Institute Tongji UniversityQingdao 266071China State key laboratory of Natural medicines China Pharmaceutical UniversityNanjing 210009China

Dear Editor,Two distinct pathways,non-homologous end joining(NHEJ)and homologous recombination(HR)repair,have evolved to repair DNA double-strand breaks(DSBs),the most deleterious type of DNA damage.Impaired NHEJ and HR are often associated with a high incidence of tumorigenesis and the early onset of aging.A number of methods and tools have been developed to help elucidate the regulatory mechanisms of the two repair pathways in the past.In vitro biochemical assays employ 32P-labeled broken DNA fragments and cell extracts to evaluate DSB repair capacity.At DSB sites,several DSB repair factors form foci,which can be visualized through immunofluorescence and microscopy.Among them,phosphorylated H2AX at the Ser139 residue is often considered a DSB marker,and its formation and removal at different time points post the induction of DSBs can be used to reflect the repair capacity and genomic instability.In addition,by quantifying the kinetics of the recruitment of specific NHEJ and HR factors such as 53BP1,DNA-PKcs,MRE11,RPA2,and RAD51,one would be able to make judgments on whether NHEJ,HR,or both pathways is/are affected and sometimes at which steps DSB repair pathways are regulated.An alternative approach for kinetic analysis is to quantify the microirradiation-induced recruitment of repair factors.Moreover,comet assays are also utilized to measure DNA damage-induced genomic stability at the single-cell level.However,with these assays,it is still difficult to measure NHEJ and HR efficiency in a relatively less time-consuming and more quantitative manner.

关键词： double repair simultaneous

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Delivery room resuscitation intensity and associated neonatal outcomes of 24^(+0)-31^(+6) weeks'preterm infants in China:a retrospective cross-sectional study

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World Journal of Pediatrics 2024年第1期20卷 64-72页

作者： Si-Lu Wang Chun Chen Xin-Yue Gu Zhao-Qing Yin Le Su Si-Yuan Jiang Yun Cao Li-Zhong Du Jian-Hua Sun Jiang-Qin Liu Chuan-Zhong Yang Department of Neonatology Shanghai Key Laboratory of Maternal Fetal MedicineShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityNo.2699Gaoke Western RoadPudong DistrictShanghai 201204China Department of Neonatology Affiliated Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityNo.2004Hongli RoadFutian DistrictShenzhen 518028China NHC key laboratory of Neonatal Diseases Fudan UniversityChildren's Hospital of Fudan UniversityShanghaiChina Department of Neonatology People's Hospital of DehongKunming Medical UniversityDehongChina Department of Neonatology Children's Hospital of Fudan UniversityShanghaiChina Department of Neonatology Children's HospitalZhejiang University School of MedicineHangzhouChina Department of Neonatology Shanghai Children's Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background The aim of this study was to review current delivery room(DR)resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0_31+6 weeks gestation age(GA).Methods This was a retrospective cross-sectional study.The source population was infants born at 24+0_31+6 weeks'GA who were enrolled in the Chinese Neonatal Network 2019 cohort.Eligible infants were categorized into five groups:(1)regular care;(2)oxygen supplementation and/or continuous positive airway pressure(O2/CPAP);(3)mask ventilation;(4)endotracheal intubation;and(5)cardiopulmonary resuscitation(CPR).The association between DR resuscitation and shortterm outcomes was evaluated by inverse propensity score-weighted logistic regression.Results Of 7939 infants included in this cohort,2419(30.5%)received regular care,1994(25.1%)received O,/CPAP,1436(18.1%)received mask ventilation,1769(22.3%)received endotracheal intubation,and 321(4.0%)received CPR in the DR.Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation,and antenatal steroid use tended to be associated with a lower need for resuscitation(P<0.001).Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors.Resuscitation strategies vary widely between centers,with over 50%of preterm infants in eight centers requiring higher intensity resuscitation.Conclusions Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China.There is wide variation in resuscitative approaches across delivery centers,and ongoing quality improvement to standardize resuscitation practices is needed.

关键词： Cardiopulmonary resuscitation Delivery room Endotracheal intubation Neonatal resuscitation Preterm

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Evidence-Based Screening, Diagnosis and Management of fetal Growth Restriction: Challenges and Confusions

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maternal-fetal medicine 2022年第3期4卷 159-161页

作者： Luming Sun Dick Oepkes Shanghai Key Laboratory of Maternal Fetal Medicine Department of Fetal Medicine&Prenatal Diagnosis CenterShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China Division of fetal medicine Department of ObstetricsLeiden University Medical CenterLeiden 2333ZAThe Netherlands

fetal growth restriction(FGR)describes a pathological condition in which the fetus fails to fulfill its growth potential.FGR is associated with higher perinatal mortality and morbidity rates as well as a variety of long-term adverse outcomes.1–4 Unfortunately,consensus is still lacking regarding the definition and diagnostic criteria of FGR,despite the recent publication of guidelines from the American College of Obstetricians and Gynecologists Committee,5 International Society of Ultrasound in Obstetrics and Gynecology,6 Society for maternal-fetal medicine,7 and the International Federation of Gynecology and Obstetrics.8 Further well-designed and prospective clinical studies are needed to fill in knowledge gaps in the areas of screening,prevention,surveillance,diagnosis,and clinical management for FGR fetuses.In this issue,we introduce a Chinese expert consensus on FGR(Matern fetal Med 2022;4(3):162-168)based on three-round Delphi procedures among multidisciplinary experts and organized by the Society of Chinese Perinatal medicine,and five reviews related to several hot topics of FGR。

关键词： fetus prevention diagnosis

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