Adriamycin induces H2AX phosphorylation in human spermatozoa

瞄准：调查 adriamycin 是否导致 DNA 损坏和 γH2AX 的形成(phosphorylated 形式嘘一 H2AX ) 在成熟精子的 foci。方法：人的精子在不同集中与 adriamycin 被对待。γH2AX 被免疫分析荧光灯的染色和流动 cytometry 和双海滨裂缝(DSB ) 被彗星试金检测。结果：中立彗星试金表明有在在不同时间(0.5， 2， 8 和 24 h ) ，或为在不同集中(0.4， 2 和 10 μg/mL ) 的 8 h 的 2 μg/mL 的 adriamycin 的处理，在精子的导致的重要 DSB。染色的 Immunofluorent 和流动 cytometry 证明 γH2AX 的表示在 adriamycin 的处理以后在一个剂量依赖者和时间家属举止被增加。Adriamycin 也在精子与 γH2AX 导致了 DNA 维护 / 修理蛋白质 RAD50 和 53BP1 的并发的外观。Wortmannin， phosphatidylinositol 3-kinase (PI3K ) 的一个禁止者家庭，与 γH2AX 废除了这二蛋白质的合作外观。结论：人的成熟精子作为体的房间有一样的反应到导致 DSB 的 H2AX phosphorylation 和 DNA maintenance/ 修理蛋白质的随后的招募。

Preimplantation genetic testing guidelines of International Society of Reproductive Genetics

The International Society of Reproductive Genetics(ISRG)assembled a workgroup made up of clinicians,clinical laboratory directors,and scientists for the purpose of creating the guidelines for preimplantation genetic testing(PGT).The most up-to-date information and clinical insights for the optimal PGT practice were incorporated in these guidelines.Recommendations are provided for embryologists,medical geneticists,clinical laboratorians,and other healthcare providers to improve the wellbeing of patients seeking assisted reproductive treatment and their offspring.

Executive Editor-in-Chief’s introduction for This Special Issue

As an Executive Editor-in-Chief,I have edited this Special Issue(SI),entitled“Preimplantation genetic testing(PGT)”published in the journal of Reproductive and Developmental Medicine(RDM;ISSN:2096-2924,CN:10-1442/R),the firstever English journal in the field of reproductive medicine and developmental biology in China's Mainland.Since its launch in 2017,the RDM has been dedicated to providing a good platform for academic exchanges among scientists,both domestically and abroad.

Association between gestational anemia in different trimesters and neonatal outcomes:a retrospective longitudinal cohort study

Background Previous studies investigated the association between gestational anemia and neonatal outcomes.However,few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy.This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes.Methods The study was conducted in Shanghai,China,with a sample of 46,578 pregnant women who delivered between January 1,2016 and July 1,2019.A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes.Results The incidence of gestational anemia was 30.2%,including 4.4%in the first trimester,9.6%in the second trimester,and 16.2%in the third trimester.Only 24.5%(507/2066)of anemia that occurred in the first trimester and 29.6%(1320/4457)that occurred in the second trimester could be corrected in the later stages of pregnancy.Anemia occurring in the first trimester was associated with small for gestational age[odds ratio(OR)1.46;95%confidence interval(CI)1.20-1.78]and with fetal distress(OR 1.23;95%CI 1.08-1.40).Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age.Conclusions Gestational anemia is a public health problem in China impacting neonatal health.Anemia in pregnancy could be corrected in only about a quarter of the women.Anemia in the first trimester,whether corrected or not,still led to lower birth weight;therefore,the prevention of anemia prior to pregnancy is important.

Long interpregnancy interval and adverse perinatal outcomes: a retrospective cohort study

We conducted a retrospective cohort study of 9,552 women experiencing their second delivery between 2014 and 2016 at the International Peace Maternity and Child Health Hospital to investigate the association between the interpregnancy interval(IPI)and adverse perinatal outcomes. With the 12–23-mon IPI as the reference category, logistic regression analyzes were used to examine associations between different IPIs(<12, 12–23, 24–59, 60–119, and ≥120 mon) and perinatal outcomes(gestational diabetes mellitus, premature membrane rupture, gestational hypertension, preterm birth, low birth weight, and macrosomia).Compared with the 12–23-mon IPI category, women with longer IPIs had a higher risk of adverse perinatal outcomes, and those with an IPI ≥120 mon had the highest risk of gestational diabetes mellitus and premature membrane rupture(adjusted odds ratio(OR) 1.76, 95% confidence interval(CI) 1.32–2.35 and adjusted OR 2.03, 95% CI 1.53–2.67, respectively). These results indicate that a longer IPI is associated with a higher risk of adverse perinatal outcomes and an IPI of ≥120 mon appears to be independently associated with a higher risk of gestational diabetes mellitus and premature membrane rupture.

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice

Intracytoplasmic sperm injection (ICSI) is commonly used to solve male infertility problems. Previous studies showed that early environmental exposure of an embryo may influence postnatal development. To detect whether ICSI operations affect the reproductive health of a male or his offspring, we established assisted reproductive technologies (ART) conceived mouse models, and analyzed gene expression profiles in the testes of both ICSI and naturally conceived (NC) newborn F1 mice using micro-array analysis. Among the differentially expressed genes, we focused on the expression of eight male reproduction-related genes. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze the expression of these genes in the testes of both adult and old F1 generation mice and adult F2 generation mice. Our results showed that down-regulated and somatic cell-expressed genes in newborn mice retained their differential expression patterns in adult and old F1 generation individuals, implying the persistence and fetal origin of the alteration in the expression of these genes. The intergenerational transmission of differential gene expression was observed, but most changes tended to be reduced in adult F2 generations. Controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) mice models were added to explore the precise factors contributing to the differences in ICSI offspring. The data demonstrated that superovulation, in vitro culture, and mechanical stimulation involved in ICSI had a cumulative effect on the differential expression of these male reproductive genes.

Associations of Prepregnancy Body Mass Index,Gestational Weight Gain,and Intelligence in Offspring:A Systematic Review and Meta-Analysis

Objective:Increasing evidences have shown that prepregnancy maternal weight and gestational weight gain(GWG)may associate with offspring’s neurodevelopment.However,the effects of prepregnancy maternal overweight,obesity,and excessive GWG on offspring’s intelligence remain controversial.This meta-analysis aimed to re-assess the association between prepregnancy body mass index(BMI),GWG,and children’s intelligence.Methods:We systematically searched multiple databases,including PubMed,EMBASE,Cochrane Library,and Ovid Medline,from their inception through February 2021.Studies assessing the association between prepregnancy BMI or GWG and children’s intelligence were further screened manually before final inclusion.Cohorts that analyzed the association between prepregnancy BMI or GWG and intelligence of offspring were included,and we used the Mantel-Haenszel fixed-effects method to compute the weighted mean difference(WMD)and 95%confidence interval(CI)of each study.Results:A total of 12 articles were included in this systematic review,while six of them in the meta-analysis.There was a significant full-scale IQ reduction in children born from overweight and obese mothers,with WMDs of-3.08(95%CI:-4.02,-2.14)and-4.91(95%CI:-6.40,-3.42),respectively.Compared with control group,the WMDs for performance and verbal intelligence quotient(IQ)were decreased in overweight and obesity groups.However,we observed no association between children’s full-scale IQ and excessive GWG with WMD of-0.14(95%CI:-0.92,0.65).Conclusions:Women’s prepregnancy overweight and obesity adversely associate with children’s intelligence but no association with excessive GWG.Our study suggests that further researches focusing on the effect of prepregnancy maternal health on offspring’s intelligence development are needed.

Year-end academic review of 2021: Advances in the field of birth defect prevention and control in China as of 2021

Birth defects,also known as congenital anomalies and malformations,may cause death of fetuses and infants,result in illness and long-term disability in children,and seriously affect the well-being of the population.Birth defects are a major public health concern in many countries worldwide,and we face severe challenges in preventing and controlling them.

Different sperm sources and parameters can influence intracytoplasmic sperm injection outcomes before embryo implantation

To evaluate the effects of sperm with different parameters and sources on the outcomes of intracytoplasmic sperm injection (ICSI), 1972 ICSI cycles were analyzed retrospectively. Groups 1 to 5 were composed of cycles using ejaculated sperm and were grouped according to sperm quantity, quality, and morphology into normal (288 cycles), or mild (329 cycles), moderate (522 cycles), severe (332 cycles), and extremely severe (171 cycles) oligozoospermia and/or asthenozoospermia and/or teratozoospermia (OAT) groups. Group 6 was composed of 250 cycles using testicular or epididymal sperm, and Group 7 consisted of 80 cycles using frozen-thawed sperm. We found that fertilization rates were gradually reduced from Groups 1 to 6, and reached statistical difference in Groups 5 and 6 (P<0.05). The high-quality embryo rate was higher in Group 1 than in Groups 2, 3, 5, 6, and 7 (P<0.05). No statistical differences were observed in the rates of embryo cleavage, clinical pregnancy, miscarriage, live-birth, premature birth, low birth weight, weeks of premature birth, average birth weight, or sex ratio for all seven groups (P>0.05). A total of nine cases of malformation were observed, with a malformation rate of 1.25% (9/719). In conclusion, different sperm sources and parameters can affect ICSI outcomes before embryo implantation. A full assessment of offspring malformation will require further study using a larger sample size.

Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis

Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.

Diagnostic Guidelines for Infertility

Infertility seriously endangers the reproductive health of women at childbearing age.It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse.Broadly defined,infertility includes two aspects-failure to conceive or have a live birth.This guideline only addressed content relevant to the former.It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology,Chinese Medical Association,based on relevant guidelines of the World Health Organization,the American Society for Reproductive Medicine,the National Institute for Health and Clinical Excellence,as well as the clinical practice in China.The guideline was reviewed by experts and doctors from medical institutions at all levels,which is applicable to the diagnosis of infertility by physicians in obstetrics,gynecology,and andrology at various medical institutions nationwide.

Application and Challenge of Preimplantation Genetic Testing in Reproductive Medicine

There has been a very rapid development in the area of preimplantation genetic testing(PGT)since the first baby applied PGT technology in the world was born in the last 30 years.As an alternative treatment of prenatal diagnosis,the transfer of the fetus with normal testing result has benefited many families.PGT is mainly classified into PGT for aneuploidies(PGT-A),PGT for chromosomal structural rearrangement(PGT-SR),and PGT for monogenic/single-gene defects(PGT-M).Here,we reviewed the application,development,limitations,and challenges of the current PGT in reproductive medicine.

Biallelic variants in RBM42 cause a multisystem disorder with neurological,facial,cardiac,and musculoskeletal involvement

Here,we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene.The patient is a 2-year-old female with severe central nervous system(CNs)abnormalities,hypotonia,hearing loss,congenital heart defects,and dysmorphic facial features.Familial whole-exome sequencing(WEs)reveals that the patient has two compound heterozygous variants,c.304C>T(p.R102*)and c.1312G>A(p.A438T),in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family.The p.A438T variant is in the RRM domain which impairs RBM42 pro-tein stability in vivo.Additionally,p.A438T disrupts the interaction of RBM42 with hnRNP K,which is the causa-tive gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient.The human R102*or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout△FgRbp1 in Fusarium while it was rescued by the wild-type(WT)human RBM42.A mouse model carying Rbm42 compound heterozygous variants,c.280C>T(p.Q94*)and c.1306_1308delinsACA(p.A436T),demonstrated gross fetal develop-mental defects and most of the double mutant animals died by E13.5.RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing(As).Overall,we present clinical,genetic,and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.