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International Journal of Molecular... Nov 2019Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous... (Review)
Review
Sex development is a complex process involving many genes and hormones. Defects in this process lead to Differences of Sex Development (DSD), a group of heterogeneous conditions not as rare as previously thought. Part of the obstacles in proper management of these patients is due to an incomplete understanding of the genetics programs and molecular pathways involved in sex development and DSD. Several challenges delay progress and the lack of a proper model system for the single patient severely hinders advances in understanding these diseases. The revolutionary techniques of cellular reprogramming and guided in vitro differentiation allow us now to exploit the versatility of induced pluripotent stem cells to create alternatives models for DSD, ideally on a patient-specific personalized basis.
Topics: Animals; Cellular Reprogramming Techniques; Disorders of Sex Development; Gonads; Humans; Induced Pluripotent Stem Cells; Patient-Specific Modeling; Primary Cell Culture
PubMed: 31690065
DOI: 10.3390/ijms20215495 -
The Journal of Clinical Endocrinology... Mar 2011
Topics: Adrenal Hyperplasia, Congenital; Disorders of Sex Development; Female; Genitalia; Humans; Infant, Newborn; Male; Sex Reassignment Procedures; Terminology as Topic
PubMed: 21378218
DOI: 10.1210/jcem.96.3.zeg33a -
Frontiers in Endocrinology 2021Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and... (Review)
Review
Disorders of Sex Development (DSD) are anomalies occurring in the process of fetal sexual differentiation that result in a discordance between the chromosomal sex and the sex of the gonads and/or the internal and/or external genitalia. Congenital disorders affecting adrenal function may be associated with DSD in both 46,XX and 46,XY individuals, but the pathogenic mechanisms differ. While in 46,XX cases, the adrenal steroidogenic disorder is responsible for the genital anomalies, in 46,XY patients DSD results from the associated testicular dysfunction. Primary adrenal insufficiency, characterized by a reduction in cortisol secretion and overproduction of ACTH, is the rule. In addition, patients may exhibit aldosterone deficiency leading to salt-wasting crises that may be life-threatening. The trophic effect of ACTH provokes congenital adrenal hyperplasia (CAH). Adrenal steroidogenic defects leading to 46,XX DSD are 21-hydroxylase deficiency, by far the most prevalent, and 11β-hydroxylase deficiency. Lipoid Congenital Adrenal Hyperplasia due to StAR defects, and cytochrome P450scc and P450c17 deficiencies cause DSD in 46,XY newborns. Mutations in SF1 may also result in combined adrenal and testicular failure leading to DSD in 46,XY individuals. Finally, impaired activities of 3βHSD2 or POR may lead to DSD in both 46,XX and 46,XY individuals. The pathophysiology, clinical presentation and management of the above-mentioned disorders are critically reviewed, with a special focus on the latest biomarkers and therapeutic development.
Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Disorders of Sex Development; Humans; Sex Differentiation
PubMed: 34987475
DOI: 10.3389/fendo.2021.770782 -
Best Practice & Research. Clinical... Apr 2010Disorder of sex development (DSD) presents a unique challenge, both diagnostically and in terms of acute and longer-term management. These are relatively rare conditions... (Review)
Review
Disorder of sex development (DSD) presents a unique challenge, both diagnostically and in terms of acute and longer-term management. These are relatively rare conditions usually requiring a multidisciplinary approach from the outset and the involvement of a tertiary centre for assessment and management recommendations. This article describes the structure of the multidisciplinary team (MDT) at our centre, with contributions from key members of the team regarding their individual roles. The focus is on the newborn referred for assessment of ambiguous genitalia, rather than on individuals who present in the adolescent period or at other times, although the same MDT involvement is likely to be required. The approach to the initial assessment and management is discussed and the subsequent diagnosis and follow-up presented, with emphasis on the importance of careful transition and long-term support.
Topics: Adolescent; Adult; Child; Disorders of Sex Development; Endocrinology; Female; Holistic Health; Humans; Infant; Infant, Newborn; Male; Molecular Biology; Patient Care Team; Referral and Consultation; Urology
PubMed: 20541156
DOI: 10.1016/j.beem.2010.01.006 -
Sexual Development : Genetics,... 2018
Topics: Disorders of Sex Development; Humans; Sexual Development
PubMed: 29055947
DOI: 10.1159/000480746 -
Nihon Hinyokika Gakkai Zasshi. the... Aug 1994Male pseudohermaphroditism (MPH) is a complex variety of sexual differentiation disorders characterized by deficiency of masculinization of the internal and/or external... (Review)
Review
Male pseudohermaphroditism (MPH) is a complex variety of sexual differentiation disorders characterized by deficiency of masculinization of the internal and/or external genital organs in the presence of testicular development as the male gonad. This condition is caused by embryonic failure in the processes of male sexual development, which is a sequence of mechanisms originating from the genetic sex determination triggered by the SRY gene on the Y chromosome, followed by genital sex differentiation influenced by the fetal testis. Resulting phenotypical features of MPH vary from complete female to mostly normal but with some ambiguity in the maleness. Pubertal changes are also important factors related to etiology. Recent elucidation of detailed mechanisms of male differentiation and its derangements has been achieved in the era of molecular genetics. Classical classification of MPH, mainly based on anatomical and endocrinological findings obviously needs to subject to a complete revision. The newest version of MPH classification is reviewed and discussed in relation to etiological backgrounds of each type of the disorder. Main etiological factors are: failure of the SRY and its related genes involved in the testis determination; failure of anti-mülerian hormone (AMH) for normal involution of the female duct system; disordered production or function of androgen receptors essential for the fetal differentiation of the male genital organs; 5 alpha-reductase deficiency syndrome; defective responsiveness of the testis to gonadotropin due to Leydig cell agenesis; various types of enzyme defects involved in testicular androgen biosynthesis; fetal testicular dysgenesis syndromes occurring at various stages of embryogenesis; and other less clearly defined entities of MPH. Implications are that other types of sexual differentiation disorders than MPH, such as true hermaphroditism, gonadal dysgenesis and some other disorders that have been considered to be distinct entities, may have close linkage to MPH through dysgenetic process of gonadal development with subsequent degeneration and/or tumorigenesis. Molecular basis of these probably related disorders should be elucidated in the near future and some clues to preventive measures for these genetically determined malformations are awaited.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgens; Animals; Disorders of Sex Development; Gonadal Dysgenesis; Humans; Male; Receptors, Androgen; Sex Differentiation
PubMed: 7933752
DOI: 10.5980/jpnjurol1989.85.1189 -
Evolution; International Journal of... Dec 2022Most plants and many animals are hermaphroditic; whether the same forces are responsible for hermaphroditism in both groups is unclear. The well-established drivers of...
Most plants and many animals are hermaphroditic; whether the same forces are responsible for hermaphroditism in both groups is unclear. The well-established drivers of hermaphroditism in plants (e.g., seed dispersal potential, pollination mode) have analogues in animals (e.g., larval dispersal potential, fertilization mode), allowing us to test the generality of the proposed drivers of hermaphroditism across both groups. Here, we test these theories for 1153 species of marine invertebrates, from three phyla. Species with either internal fertilization, restricted offspring dispersal, or small body sizes are more likely to be hermaphroditic than species that are external fertilizers, planktonic developers, or larger. Plants and animals show different biogeographical patterns, however: animals are less likely to be hermaphroditic at higher latitudes-the opposite to the trend in plants. Overall, our results suggest that similar forces, namely, competition among offspring or gametes, shape the evolution of hermaphroditism across plants and three invertebrate phyla.
Topics: Animals; Biological Evolution; Invertebrates; Body Size; Aquatic Organisms; Disorders of Sex Development; Plants
PubMed: 36199199
DOI: 10.1111/evo.14639 -
WormBook : the Online Review of C.... Jan 2006There are two sexes in C. elegans, hermaphrodite and male. While there are many sex-specific differences between males and hermaphrodites that affect most tissues, the... (Review)
Review
There are two sexes in C. elegans, hermaphrodite and male. While there are many sex-specific differences between males and hermaphrodites that affect most tissues, the basic body plan and many of its structures are identical. However, most structures required for mating or reproduction are sexually dimorphic and are generated by sex-specific cell lineages. Thus to understand cell fate specification in hermaphrodites, one must consider how the body plan, which is specified during embryogenesis, influences the fates individual cells. One possible mechanism may involve the asymmetric distribution of POP-1/Tcf, the sole C. elegans Tcf homolog, to anterior-posterior sister cells. Another mechanism that functions to specify cell fates along the anterior-posterior body axis in both hermaphrodites and males are the Hox genes. Since most of the cell fate specifications that occur in hermaphrodites also occur in males, the focus of this chapter will be on those that only occur in hermaphrodites. This will include the cell fate decisions that affect the HSN neurons, ventral hypodermal P cells, lateral hypodermal cells V5, V6, and T; as well as the mesodermal M, Z1, and Z4 cells and the intestinal cells. Both cell lineage-based and cell-signaling mechanisms of cell fate specification will be discussed. Only two direct targets of the sex determination pathway that influence cell fate specification to produce hermaphrodite-specific cell fates have been identified. Thus a major challenge will be to learn additional mechanisms by which the sex determination pathway interacts with signaling pathways and other cell fate specification genes to generate hermaphrodite-specific cell fates.
Topics: Animals; Caenorhabditis elegans; Cell Lineage; Disorders of Sex Development; Epidermal Cells; Epidermis; Genes, Helminth; Genes, Homeobox; Gonads; Intestines; Sex Differentiation
PubMed: 18050480
DOI: 10.1895/wormbook.1.39.1 -
Nature Aging Sep 2022Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex-hermaphrodites or females....
Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex-hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C. elegans. Some genes (for example, delm-2, acbp-3), when knocked down, are specifically protective against male-induced demise. Others (for example, sri-40), when knocked down, extend lifespan with and without males, suggesting general mechanisms of protection. In contrast, many classical long-lived mutants are impacted more negatively than wild type by the presence of males, highlighting the importance of sexual environment for longevity. Interestingly, genes induced by males are triggered by specific male components (seminal fluid, sperm and pheromone), and manipulating these genes in combination in hermaphrodites induces stronger protection. One of these genes, the conserved ion channel delm-2, acts in the nervous system and intestine to regulate lipid metabolism. Our analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers elaborate strategies elicited by sexual interactions that could extend to other species.
Topics: Animals; Female; Male; Caenorhabditis elegans; Semen; Longevity; Caenorhabditis; Spermatozoa; Disorders of Sex Development
PubMed: 37118502
DOI: 10.1038/s43587-022-00276-y -
Frontiers in Endocrinology 2024Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent... (Review)
Review
Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.
Topics: Humans; 46, XX Disorders of Sex Development; Quality of Life; Female; Male; Adrenal Hyperplasia, Congenital; Gender Identity; Disorders of Sex Development; Fertility
PubMed: 38752171
DOI: 10.3389/fendo.2024.1372887