Birth Defects Research Part C-Embryo Today-Reviews最新文献

{"title":"Wide spectrum of NR5A1-related phenotypes in 46,XY and 46,XX individuals","authors":"Sorahia Domenice,&nbsp;Aline Zamboni Machado,&nbsp;Frederico Moraes Ferreira,&nbsp;Bruno Ferraz-de-Souza,&nbsp;Antonio Marcondes Lerario,&nbsp;Lin Lin,&nbsp;Mirian Yumie Nishi,&nbsp;Nathalia Lisboa Gomes,&nbsp;Thatiana Evelin da Silva,&nbsp;Rosana Barbosa Silva,&nbsp;Rafaela Vieira Correa,&nbsp;Luciana Ribeiro Montenegro,&nbsp;Amanda Narciso,&nbsp;Elaine Maria Frade Costa,&nbsp;John C Achermann,&nbsp;Berenice Bilharinho Mendonca","doi":"10.1002/bdrc.21145","DOIUrl":"10.1002/bdrc.21145","url":null,"abstract":"<div>\u0000 <p>Steroidogenic factor 1 (NR5A1, SF-1, Ad4BP) is a transcriptional regulator of genes involved in adrenal and gonadal development and function. Mutations in <i>NR5A1</i> have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency (POI). The most common 46,XY phenotype is atypical or female external genitalia with clitoromegaly, palpable gonads, and absence of Müllerian derivatives. Notably, an undervirilized external genitalia is frequently seen at birth, while spontaneous virilization may occur later, at puberty. In 46,XX individuals, <i>NR5A1</i> mutations are a rare genetic cause of POI, manifesting as primary or secondary amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels. Mothers and sisters of 46,XY DSD patients carrying heterozygous <i>NR5A1</i> mutations may develop POI, and therefore require appropriate counseling. Moreover, the recurrent heterozygous p.Arg92Trp NR5A1 mutation is associated with variable degrees of testis development in 46,XX patients. A clear genotype-phenotype correlation is not seen in patients bearing <i>NR5A1</i> mutations, suggesting that genetic modifiers, such as pathogenic variants in other testis/ovarian-determining genes, may contribute to the phenotypic expression. Here, we review the published literature on NR5A1-related disease, and discuss our findings at a single tertiary center in Brazil, including ten novel <i>NR5A1</i> mutations identified in 46,XY DSD patients. The ever-expanding phenotypic range associated with <i>NR5A1</i> variants in XY and XX individuals confirms its pivotal role in reproductive biology, and should alert clinicians to the possibility of NR5A1 defects in a variety of phenotypes presenting with gonadal dysfunction. Birth Defects Research (Part C) 108:309–320, 2016. © 2016 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.</p>\u0000 </div>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"309-320"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51366408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction: “Sex Development”","authors":"Michiko Watanabe,&nbsp;Naveen Uli","doi":"10.1002/bdrc.21149","DOIUrl":"10.1002/bdrc.21149","url":null,"abstract":"","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"290-292"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74814060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in the diagnosis and management of disorders of sex development","authors":"Katherine Kutney,&nbsp;Laura Konczal,&nbsp;Beth Kaminski,&nbsp;Naveen Uli","doi":"10.1002/bdrc.21147","DOIUrl":"https://doi.org/10.1002/bdrc.21147","url":null,"abstract":"<p>Disorders of sex development (DSD) represent a spectrum of uncommon but very complex disorders with medical, psychosexual, and family implications for those affected by them. The diagnosis and management of these disorders requires a coordinated team of multiple specialists. Following an international conference in Chicago in 2005, a consensus statement was created and presented, which has resulted in a new paradigm in the nomenclature, classification, and management of DSDs. Since that time, many improvements have been forthcoming, most notably in the area of molecular genetic technologies. These developments have advanced our understanding of the specific etiologies underlying many of these conditions. In this article, we present an overview of the physiology of sex development, a few clinical vignettes highlighting specific pathologic conditions, discussions regarding the evaluation and management of these disorders, and some thoughts on future directions in this field. Birth Defects Research (Part C) 108:293–308, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"293-308"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sociocultural aspects of disorders of sex development","authors":"Annastasia Ediati,&nbsp;Nani Maharani,&nbsp;Agustini Utari","doi":"10.1002/bdrc.21144","DOIUrl":"https://doi.org/10.1002/bdrc.21144","url":null,"abstract":"<p>Disorders of sex development (DSD) is a congenital condition in which the development of chromosomes, gonads, hormones, and reproductive structures are atypical. DSD brings with it a psychological impact on the affected individual and their families. The consensus statement on management of DSD strongly advised an integrated and multidisciplinary approach in providing care to the affected individuals. Studies have been conducted focusing on medical intervention, and more recently, there is increasing attention paid to psychological aspects of DSD. However, studies reporting cultural aspects of DSD are lacking. This review provides an overview on how culture impacts the affected individuals in coping with DSD and making decisions with regard to gender assignment or reassignment, help-seeking behavior for medical treatments, attitudes toward medical treatment, religious beliefs, and values concerning marriage and fertility. The involvement of social scientists is needed to study sociocultural aspects of DSD from more diverse cultures, to help affected individuals and their families in gaining better social acceptance. Birth Defects Research (Part C) 108:380–383, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"380-383"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review disorders of sex development: The evolving role of genomics in diagnosis and gene discovery","authors":"Brittany Croft,&nbsp;Katie Ayers,&nbsp;Andrew Sinclair,&nbsp;Thomas Ohnesorg","doi":"10.1002/bdrc.21148","DOIUrl":"https://doi.org/10.1002/bdrc.21148","url":null,"abstract":"<p>Disorders of Sex Development (DSDs) are a major paediatric concern and are estimated to occur in around 1.7% of all live births (Fausto-Sterling, <i>Sexing the Body: Gender Politics and the Construction of Sexuality</i>, Basic Books, New York, 2000). They are often caused by the breakdown in the complex genetic mechanisms that underlie gonadal development and differentiation. Having a genetic diagnosis can be important for patients with a DSD: it can increase acceptance of a disorder often surrounded by stigma, alter clinical management and it can assist in reproductive planning. While Massively Parallel Sequencing (MPS) is advancing the genetic diagnosis of rare Mendelian disorders, it is not yet clear which MPS assay is best suited for the clinical diagnosis of DSD patients and to what extent other established methods are still relevant. To complicate matters, DSDs represent a wide spectrum of disorders caused by an array of different genetic changes, many of which are yet unknown. Here we discuss the different genetic lesions that are known to contribute to different DSDs, and review the utility of a range of MPS approaches for diagnosing DSD patients. Birth Defects Research (Part C) 108:337–350, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"337-350"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why boys will be boys and girls will be girls: Human sex development and its defects","authors":"Wassim Eid,&nbsp;Anna Biason-Lauber","doi":"10.1002/bdrc.21143","DOIUrl":"https://doi.org/10.1002/bdrc.21143","url":null,"abstract":"<p>Among the most defining events of an individual's life, is the development of a human embryo into male or a female. The phenotypic sex of an individual depends on the type of gonad that develops in the embryo, a process which itself is determined by the genetic setting of the individual. The development of the gonads is different from any other organ, as they possess the potential to differentiate into two functionally distinct organs, testes, or ovaries. Sex development can be divided into two distinctive processes, “sex determination,” which is the commitment of the undifferentiated gonad into either a testis or an ovary, a process that is genetically programmed in a critically timed manner and “sex differentiation,” which takes place through hormones produced by the gonads, once the developmental sex determination decision has been made. Disruption of any of the genes involved in either the testicular or ovarian development pathway could lead to disorders of sex development. In this review, we provide an insight into the factors important for sex determination, their antagonistic actions and whenever possible, references on the “prismatic” clinical cases are given. Birth Defects Research (Part C) 108:365–379, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"365-379"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and epigenetic effects in sex determination","authors":"Sezgin Ozgur Gunes,&nbsp;Asli Metin Mahmutoglu,&nbsp;Ashok Agarwal","doi":"10.1002/bdrc.21146","DOIUrl":"https://doi.org/10.1002/bdrc.21146","url":null,"abstract":"<p>Sex determination is a complex and dynamic process with multiple genetic and environmental causes, in which germ and somatic cells receive various sex-specific features. During the fifth week of fetal life, the bipotential embryonic gonad starts to develop in humans. In the bipotential gonadal tissue, certain cell groups start to differentiate to form the ovaries or testes. Despite considerable efforts and advances in identifying the mechanisms playing a role in sex determination and differentiation, the underlying mechanisms of the exact functions of many genes, gene–gene interactions, and epigenetic modifications that are involved in different stages of this cascade are not completely understood. This review aims at discussing current data on the genetic effects via genes and epigenetic mechanisms that affect the regulation of sex determination. Birth Defects Research (Part C) 108:321–336, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"321-336"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple exposures to environmental pollutants and oxidative stress: Is there a sex specific risk of developmental complications for fetuses?","authors":"Kaïs H. Al-Gubory","doi":"10.1002/bdrc.21142","DOIUrl":"https://doi.org/10.1002/bdrc.21142","url":null,"abstract":"<p>Medically assisted procreation significantly contributes to an increase in twin pregnancies. One of the major factors contributing to more twin births is the use of fertility treatments. Twin pregnancy is not without a risk for fetal organ development and the health outcome of new-borns, children, and adults. Multiple pregnancies are associated with an increased risk of developmental complications, such as perinatal mortality, premature births, and low birth weight. Oxidative stress is involved in pregnancy disorders such as abortion, intrauterine growth retardation, and prenatal mortality. The link between oxidative stress and prenatal development, poorly perceived in the medical community, is a major problem in human reproductive medicine and health outcomes. The sex-based considerations and analyses are also, often neglected in biomedical research. In addition, fetal sexual dimorphism in antioxidant pathways following intrauterine exposure to environmental pollutants has not been explored. This is an important area of research because sexually dimorphic antioxidant adaptive responses to early life exposure-induced oxidative stress may have long-term effects on offspring health outcome and increase the risk of non-communicable diseases in men and women. This concept is useful, since it may open the avenue to develop antenatal antioxidant therapeutic strategies to developmental disorders and complications related to multiple pregnancies, and in association with acute or chronic environmental exposure. This article reviews the status of research, supporting data, possible pathogenic mechanisms, and future perspectives in the proposed area. Birth Defects Research (Part C) 108:351–364, 2016. © 2016 Wiley Periodicals, Inc.</p>","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"108 4","pages":"351-364"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/bdrc.21142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91885812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple exposures to environmental pollutants and oxidative stress: Is there a sex specific risk of developmental complications for fetuses?","authors":"K. H. Al-Gubory","doi":"10.1002/bdrc.21142","DOIUrl":"https://doi.org/10.1002/bdrc.21142","url":null,"abstract":"Medically assisted procreation significantly contributes to an increase in twin pregnancies. One of the major factors contributing to more twin births is the use of fertility treatments. Twin pregnancy is not without a risk for fetal organ development and the health outcome of new-borns, children, and adults. Multiple pregnancies are associated with an increased risk of developmental complications, such as perinatal mortality, premature births, and low birth weight. Oxidative stress is involved in pregnancy disorders such as abortion, intrauterine growth retardation, and prenatal mortality. The link between oxidative stress and prenatal development, poorly perceived in the medical community, is a major problem in human reproductive medicine and health outcomes. The sex-based considerations and analyses are also, often neglected in biomedical research. In addition, fetal sexual dimorphism in antioxidant pathways following intrauterine exposure to environmental pollutants has not been explored. This is an important area of research because sexually dimorphic antioxidant adaptive responses to early life exposure-induced oxidative stress may have long-term effects on offspring health outcome and increase the risk of non-communicable diseases in men and women. This concept is useful, since it may open the avenue to develop antenatal antioxidant therapeutic strategies to developmental disorders and complications related to multiple pregnancies, and in association with acute or chronic environmental exposure. This article reviews the status of research, supporting data, possible pathogenic mechanisms, and future perspectives in the proposed area. Birth Defects Research (Part C) 108:351-364, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"41 1","pages":"351-364"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85939992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review disorders of sex development: The evolving role of genomics in diagnosis and gene discovery.","authors":"Brittany Croft, K. Ayers, A. Sinclair, T. Ohnesorg","doi":"10.1002/bdrc.21148","DOIUrl":"https://doi.org/10.1002/bdrc.21148","url":null,"abstract":"Disorders of Sex Development (DSDs) are a major paediatric concern and are estimated to occur in around 1.7% of all live births (Fausto-Sterling, Sexing the Body: Gender Politics and the Construction of Sexuality, Basic Books, New York, 2000). They are often caused by the breakdown in the complex genetic mechanisms that underlie gonadal development and differentiation. Having a genetic diagnosis can be important for patients with a DSD: it can increase acceptance of a disorder often surrounded by stigma, alter clinical management and it can assist in reproductive planning. While Massively Parallel Sequencing (MPS) is advancing the genetic diagnosis of rare Mendelian disorders, it is not yet clear which MPS assay is best suited for the clinical diagnosis of DSD patients and to what extent other established methods are still relevant. To complicate matters, DSDs represent a wide spectrum of disorders caused by an array of different genetic changes, many of which are yet unknown. Here we discuss the different genetic lesions that are known to contribute to different DSDs, and review the utility of a range of MPS approaches for diagnosing DSD patients. Birth Defects Research (Part C) 108:337-350, 2016. © 2016 Wiley Periodicals, Inc.","PeriodicalId":55352,"journal":{"name":"Birth Defects Research Part C-Embryo Today-Reviews","volume":"37 1","pages":"337-350"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81210618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}