Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examin...Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.展开更多
Childhood sexual abuse(CSA)is a widespread and serious public health concern,with long-term impacts on overall health in adulthood.According to a systematic review published in 2018,the prevalence of CSA in China rang...Childhood sexual abuse(CSA)is a widespread and serious public health concern,with long-term impacts on overall health in adulthood.According to a systematic review published in 2018,the prevalence of CSA in China ranges from 11.6%to 20.2%[1].A longitudinal study from New Zealand demonstrated that CSA negatively influences a broad range of adult developmental outcomes,including mental disorders,psychological wellbeing,sexual risk-taking,physical health,and socioeconomic wellbeing[2].Therefore,CSA is considered a longterm hazard to the overall health of adults and is associated with poor quality of life(QoL).展开更多
Self-inflicted and interpersonal violence are the two main types of adolescent violence.Individuals involved in self-inflicted violence both cause and receive the harm,while those who engage in interpersonal violence ...Self-inflicted and interpersonal violence are the two main types of adolescent violence.Individuals involved in self-inflicted violence both cause and receive the harm,while those who engage in interpersonal violence often aim to harm others.Self-harm and suicide are common types of selfinflicted violence.Non-fatal violence,such as aggression,bullying,and physical fighting,are common forms of interpersonal violence between adolescents[1].展开更多
Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in s...Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.展开更多
The beginning of a mammalian life commences with a fertilized oocyte.The study of oocytes is certainly one of the most intriguing scientific questions of our time.Herein,we studied oocytes from a mechanical perspectiv...The beginning of a mammalian life commences with a fertilized oocyte.The study of oocytes is certainly one of the most intriguing scientific questions of our time.Herein,we studied oocytes from a mechanical perspective and characterized the typical life activities of oocytes by nanomechanical vibrations.During the development of oocytes from the germinal vesicle(GV)stage to the zygotes,the GV stage oocytes induced a significant nanomechanical vibration,compared with the oocytes in meiosis I(MI)and meiosis II(MII)stages and zygotes.We analyzed the characteristics of mechanical vibrations of oocytes,including the amplitude as well as the frequency.It showed that the amplitude and frequency of nanomechanical vibrations induced by oocytes were caused by the cytoskeleton(microfilaments)and the distribution of metabolic characteristics(mitochondria)within oocytes.This work provides a new perspective for clinical quality assessment and basic research of oocytes,and can open new doors for development of life science.展开更多
Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermato...Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).展开更多
Acephalic spermatozoa syndrome(ASS)is one of the most severe spermatogenic failures of all infertility in men.The cognition of ASS has experienced a tortuous process.Over the past years,with the in-depth understanding...Acephalic spermatozoa syndrome(ASS)is one of the most severe spermatogenic failures of all infertility in men.The cognition of ASS has experienced a tortuous process.Over the past years,with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies,the unraveling of the genetic causes of spermatogenic failure has become highly active.From these advances,we established a genetic background and made significant progress in the discovery of the genetic causes of ASS.It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome.In this review,we enumerate various technological developments,which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present.Simultaneously,we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present.Furthermore,we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.展开更多
Dear Editor,The first mitotic division in zygotes is crucial for the beginning of the life cycle for the human.After fertilization,zygotes reactivate cell cycle,both paternal and maternal genomes replicate and reprogr...Dear Editor,The first mitotic division in zygotes is crucial for the beginning of the life cycle for the human.After fertilization,zygotes reactivate cell cycle,both paternal and maternal genomes replicate and reprogram to become totipotent.In the meantime,the male and female pronucleus move to the center of the zygote and merge.Then zygotes enter the metaphase,and sister chromatids separate into two daughter cells(Eckersley-Maslin et al.,2018;Reichmann et al.,2018).This is a sensitive time window and many perturbances may cause the first mitosis to fail.展开更多
The axoneme of the human sperm has a very similar ultrastructure to motile cilia,the"9+2"structure,comprising nine peripheral double microtubules plus two central pairs(Nicastro et al.,2006;Ishikawa,2017).A ...The axoneme of the human sperm has a very similar ultrastructure to motile cilia,the"9+2"structure,comprising nine peripheral double microtubules plus two central pairs(Nicastro et al.,2006;Ishikawa,2017).A proteomics analysis identified more than700 proteins exclusively in the sperm tail,and abnormal expression of related genes can cause male infertility with multiple morphological abnormalities of flagella(MMAF),including absent,coiled,short,and irregular-caliber flagella(Baker et al.,2013;Coutton et al.,2015).展开更多
Dear Editor, In nature or during artificial breeding,evolutionary interven-tion or desirable trait selection could be achieved by means of gender control in an organism.Previously reported approaches including sex-sor...Dear Editor, In nature or during artificial breeding,evolutionary interven-tion or desirable trait selection could be achieved by means of gender control in an organism.Previously reported approaches including sex-sorted semen and genetic manipulation of a certain gene(Holden and Butler,2018;Yosef et al.,2019).In mice,a recent study demonstrated a genetic system for biasing sex ratio through crossing two genetically engineered mouse lines(Yosef et al.,2019).The maternal line encodes functional Cas9 protein on an auto-somal chromosome,whereas the paternal encodes guide RNAs on Y chromosome targeting vital genes.After fertil-ization,males carrying both Cas9 and guide RNAs were self-destructed,resulting in a female biased sex ratio.However,the litter size is proximate half of normal size since half of the progeny are eliminated.Moreover,a reproductive reservoir of males and females must be maintained for crossing.Here,we established a mouse line carrying Hspa2 promoted Cas9 and constitutively expressed sgRNA targeting repetitive sequences on Y chromosome.In those mice,spermatogenic cells carrying Y chromosome were eliminated during sper-matogenesis,resulting in female biased sex ratio in proge-nies whereas the total number was unaffected.展开更多
Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human diseases.Ivs2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of...Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human diseases.Ivs2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of the most common diseases in Southeast Asia and China."In our previous work,we found a TTTV protospacer adjacent motif(PAM)by the Cas12a system and the editing efficiency of Ivs2-654 C>T achieving 76.7%.展开更多
基金supported by the National Natural Science Foundation of China [82073566 and 82073578]the Program for Excellent Young Talents in College and University of Anhui Province [gxyq2019014]+1 种基金the Clinical Scientific Research Project of Anhui Medical University [2020xkj161]the Anhui Medical University Clinical Pharmacology and Pharmacology Co-construction Project (2020)
文摘Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.
基金funded by grants from the National Natural Science Foundation of China[grant numbers:82204071,81874268,and 82173539]a Scientific Research of BSKY grant from Anhui Medical University[grant number:0303033201].
文摘Childhood sexual abuse(CSA)is a widespread and serious public health concern,with long-term impacts on overall health in adulthood.According to a systematic review published in 2018,the prevalence of CSA in China ranges from 11.6%to 20.2%[1].A longitudinal study from New Zealand demonstrated that CSA negatively influences a broad range of adult developmental outcomes,including mental disorders,psychological wellbeing,sexual risk-taking,physical health,and socioeconomic wellbeing[2].Therefore,CSA is considered a longterm hazard to the overall health of adults and is associated with poor quality of life(QoL).
基金supported by grants from the National Nature Science Foundation of China 81874268,81573163,81673188College Students’ Innovation Project Foundation of Anhui Province in China grants number S201910366051。
文摘Self-inflicted and interpersonal violence are the two main types of adolescent violence.Individuals involved in self-inflicted violence both cause and receive the harm,while those who engage in interpersonal violence often aim to harm others.Self-harm and suicide are common types of selfinflicted violence.Non-fatal violence,such as aggression,bullying,and physical fighting,are common forms of interpersonal violence between adolescents[1].
基金This work was supported by the National Natural Science Foundation of China(No.82071705)University Outstanding Youth Program of Anhui Provincial Education Department(2022AH030113)+1 种基金University Outstanding Young Talents Support Program(gxyq2021174)Postgraduate Innovation Research and Practice Program of Anhui Medical University(No.YJS20210327).
文摘Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.
基金the National Natural Science Foundation of China(Nos.11627803,32061160475,and 11872355).
文摘The beginning of a mammalian life commences with a fertilized oocyte.The study of oocytes is certainly one of the most intriguing scientific questions of our time.Herein,we studied oocytes from a mechanical perspective and characterized the typical life activities of oocytes by nanomechanical vibrations.During the development of oocytes from the germinal vesicle(GV)stage to the zygotes,the GV stage oocytes induced a significant nanomechanical vibration,compared with the oocytes in meiosis I(MI)and meiosis II(MII)stages and zygotes.We analyzed the characteristics of mechanical vibrations of oocytes,including the amplitude as well as the frequency.It showed that the amplitude and frequency of nanomechanical vibrations induced by oocytes were caused by the cytoskeleton(microfilaments)and the distribution of metabolic characteristics(mitochondria)within oocytes.This work provides a new perspective for clinical quality assessment and basic research of oocytes,and can open new doors for development of life science.
基金supported by the National Key Research and Development Program of China(2021YFC2701400 and 2021YFC2700901)the National Natural Science Foundation of China(32100480,82171607,and 81971441)+4 种基金the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Scientific Research(TP202002)from Anhui Medical Universitythe China Postdoctoral Science Foundation(2020TQ0072)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310002)supported by Shanghai Municipal Commission for Science and Technology Grants(19411951800)。
文摘Male infertility is a complex reproductive disorder that impedes a huge number of couples from having children naturally in the world(Agarwal et al.,2021).As an important pathogenic factor of male infertility,spermatogenic impairments are mainly characterized by impaired male gamete production,reduced sperm quality,or function(Tournaye et al.,2017).Spermatogenesis is a delicate and complex biological process that requires the collaboration of a large number of proteins performing different biological functions(Liu et al.,2021).
文摘Acephalic spermatozoa syndrome(ASS)is one of the most severe spermatogenic failures of all infertility in men.The cognition of ASS has experienced a tortuous process.Over the past years,with the in-depth understanding of spermatogenesis and the emergence of new genetic research technologies,the unraveling of the genetic causes of spermatogenic failure has become highly active.From these advances,we established a genetic background and made significant progress in the discovery of the genetic causes of ASS.It is important to identify pathogenic genes and mutations in ASS to determine the biological reasons for the occurrence of the disease as well as provide genetic diagnosis and treatment strategies for patients with this syndrome.In this review,we enumerate various technological developments,which have made a positive contribution to the discovery of candidate genes for ASS from the past to the present.Simultaneously,we summarize the known genetic etiology of this phenotype and the clinical outcomes of treatments in the present.Furthermore,we propose perspectives for further study and application of genetic diagnosis and assisted reproductive treatment in the future.
基金This work was supported by the National Key R&D Program of China(Grant 2019YFA0110001,2017YFA0102802)the National Natural Science Foundation of China(Grant Nos.31970819,91740115,31771108 to JN,Grant No.32000610 to JG,82001516 to BC,and 82071724 to ZZ)+2 种基金Beijing Hospitals Authority Youth Programme QML20201401 to LLJG is supported by the Tsinghua-Peking Center for Life Sciences postdoctoral fellowshipTsinghua University SRT grant 2111S0057 and 2111T0626 to QL and JN.
文摘Dear Editor,The first mitotic division in zygotes is crucial for the beginning of the life cycle for the human.After fertilization,zygotes reactivate cell cycle,both paternal and maternal genomes replicate and reprogram to become totipotent.In the meantime,the male and female pronucleus move to the center of the zygote and merge.Then zygotes enter the metaphase,and sister chromatids separate into two daughter cells(Eckersley-Maslin et al.,2018;Reichmann et al.,2018).This is a sensitive time window and many perturbances may cause the first mitosis to fail.
基金supported by the National Natural Science Foundation of China(81971441,31625015,and 31521003)Foundation of the Education Department of Anhui Province(KJ2019A0286)Key R&D program of Anhui Province(202004j07020032)
文摘The axoneme of the human sperm has a very similar ultrastructure to motile cilia,the"9+2"structure,comprising nine peripheral double microtubules plus two central pairs(Nicastro et al.,2006;Ishikawa,2017).A proteomics analysis identified more than700 proteins exclusively in the sperm tail,and abnormal expression of related genes can cause male infertility with multiple morphological abnormalities of flagella(MMAF),including absent,coiled,short,and irregular-caliber flagella(Baker et al.,2013;Coutton et al.,2015).
基金supported by the National Key R&D Program of China(2019YFA0109900,2019YFA0802800)The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(11300-412214-20009)+4 种基金the Innovation program of Shanghai Municipal Education Commission(2019-01-07-00-05-E00054)Shanghai pujiang program(11300-412213-19B08)the Scientific Research of BSKY(XJ2020025)from Anhui Medical Universitythe National Natural Science Foundation of China(82101802)Natural Science Foundation of Anhui province Department of Education(KJ2020A0205).
文摘Dear Editor, In nature or during artificial breeding,evolutionary interven-tion or desirable trait selection could be achieved by means of gender control in an organism.Previously reported approaches including sex-sorted semen and genetic manipulation of a certain gene(Holden and Butler,2018;Yosef et al.,2019).In mice,a recent study demonstrated a genetic system for biasing sex ratio through crossing two genetically engineered mouse lines(Yosef et al.,2019).The maternal line encodes functional Cas9 protein on an auto-somal chromosome,whereas the paternal encodes guide RNAs on Y chromosome targeting vital genes.After fertil-ization,males carrying both Cas9 and guide RNAs were self-destructed,resulting in a female biased sex ratio.However,the litter size is proximate half of normal size since half of the progeny are eliminated.Moreover,a reproductive reservoir of males and females must be maintained for crossing.Here,we established a mouse line carrying Hspa2 promoted Cas9 and constitutively expressed sgRNA targeting repetitive sequences on Y chromosome.In those mice,spermatogenic cells carrying Y chromosome were eliminated during sper-matogenesis,resulting in female biased sex ratio in proge-nies whereas the total number was unaffected.
基金supported by the National Key R&D Program ofChina(No.2019YFA0109900,2019YFA0109901,2019YFA0802800,2019YFA0110803,2021YFC2700901)the Shanghai Municipal Commission for Science and Technology(No.19PJ1403500)+3 种基金the National Natural Science Foundation of China(No.82101802,81300383)the Scientific Research of BSKY(No.XJ2020025)from Anhui Medical University,and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2019PT310002)Young Taishan Scholar Foundation of Shandong Province,China(No.tsqn202103167)Clinical Research Center of Shandong University(China)(No.2020SDUCRCC015).
文摘Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human diseases.Ivs2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of the most common diseases in Southeast Asia and China."In our previous work,we found a TTTV protospacer adjacent motif(PAM)by the Cas12a system and the editing efficiency of Ivs2-654 C>T achieving 76.7%.
