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

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.

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.

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.

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.

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.

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.