-
Journal of Clinical Medicine Nov 2020In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification... (Review)
Review
In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification of disorders or anomalies of sex development. Anomalies in sex determination without sex ambiguity include gonadal dysgenesis, polysomies, male XX, and Klinefelter syndrome (dysgenesis and polysomies with a female phenotype; and sex reversal and Klinefelter with a male phenotype). Other infertility situations could also be included here as minor degrees of dysgenesis. Anomalies in sex determination with sex ambiguity should (usually) include testicular dysgenesis and ovotesticular disorders. Among the anomalies in sex differentiation, we include: (1) males with androgen deficiency (MAD) that correspond to those individuals whose karyotype and gonads are male (XY and testes), but the phenotype can be female due to different hormonal abnormalities. (2) females with androgen excess (FAE); these patients have ovaries and a 46,XX karyotype, but present varying degrees of external genital virilization as a result of an enzyme abnormality that affects adrenal steroid biosynthesis and leads to congenital adrenal hyperplasia; less frequently, this can be caused by iatrogenia or tumors. (3) Kallman syndrome. All of these anomalies are reviewed and analyzed herein, as well as related fertility problems.
PubMed: 33158283
DOI: 10.3390/jcm9113555 -
Archives of Sexual Behavior May 2024False claims of having an intersex condition have been observed in print, video, Internet media, and in live presentations. Claims of being intersexed in publicly...
False claims of having an intersex condition have been observed in print, video, Internet media, and in live presentations. Claims of being intersexed in publicly accessible media were examined and evidence that they were false was considered sufficiently conclusive in 37 cases. Falsity was most often detected due to medical implausibility and/or inconsistency, but sometimes also using information from third-party or published sources. The majority, 26/37, of cases were natal males; 11/37 were natal females. Almost all (34/37) were transgendered, living, or aspiring to live, in their non-natal sex or as socially intergender. The most commonly claimed diagnosis was ovotesticular disorder ("true hermaphroditism") due to chimerism, an actually uncommon cause of authentic intersexuality. Motivations for pretending to be intersexed were inferred from statements and behaviors and were varied. Some such pretenders appear to be avoiding the external or internalized stigma of an actual transgendered condition. Some appear, similarly to persons with factitious disorder, to be seeking attention and/or the role of a sick, disadvantaged, or victimized person. Some showed evidence of paraphilia, most frequently autogynephilia, and, in several cases, paraphilic diaperism. For some cases, such claims had been accepted as authentic by journalists or social scientists and repeated as true in published material.
Topics: Humans; Female; Male; Disorders of Sex Development; Transgender Persons
PubMed: 38744731
DOI: 10.1007/s10508-024-02854-0 -
Cell Death & Disease Apr 2021Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is...
Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. We provide an overview of cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by degradation of female germline cells via liquid-liquid phase separation of the proteasomes in the nucleus, and impaired histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germlines synergistically determined distinct cell fate of both male and female germlines. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation direction of ovotestis, and provide novel insights into ovotestis development.
Topics: Animals; Cell Differentiation; Female; Germ Cells; Male; Sexual Selection
PubMed: 33846307
DOI: 10.1038/s41419-021-03676-x -
PeerJ 2023Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different...
Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different organismal levels, including major storage organs (liver, kidneys), key organs for species survival (gonads), and epigenetic networks regulating gene expression. 5-methylcytosine (5mC) is the most common and best-characterized epigenetic mark among different modified nucleosides in DNA. This important player in methylation-driven gene expression is impacted by cadmium in sentinel terrestrial vertebrates. However, limited information exists regarding its impact on macroinvertebrates, especially land snails commonly used as (eco)toxicological models. We first investigate the methylomic effects of dietary cadmium given as cadmium nitrate on terrestrial mollusks. Mature specimens of the common brown garden snail, , were continuously exposed for four weeks to environmentally-relevant cadmium levels. We determined global genomic DNA methylation in hepatopancreas and ovotestis, as well as changes in the methylation status of CG pairs at the 5' region close to the transcription site of gene encoding the Cd-selective metallothionein (Cd-MT). Weight gain/loss, hypometabolism tendency, and survival rates were also assessed. Although this exposure event did not adversely affect survival, gastropods exposed to the highest Cd dose revealed a significant reduction in body weight and a significant increase in hypometabolic behavior. The hepatopancreas, but not the ovotestis, displayed significant hypermethylation, but only for the aforementioned specimens. We also found that the 5' end of the gene was unmethylated in both organs and its methylation status was insensitive to cadmium exposure. Our results are important since they provide scientists, for the first time, with quantitative data on DNA methylation in gastropod ovotestis and refine our understanding of Cd epigenetic effects on terrestrial mollusks.
Topics: Animals; Cadmium; DNA Methylation; Hepatopancreas; Cadmium Compounds
PubMed: 37073276
DOI: 10.7717/peerj.15032 -
Annual Review of Animal Biosciences Feb 2023Talpid moles and spotted hyenas have become the paradigms of anatomical and behavioral female masculinization. Females of many mole species develop ovotestes that... (Review)
Review
Talpid moles and spotted hyenas have become the paradigms of anatomical and behavioral female masculinization. Females of many mole species develop ovotestes that produce testosterone, show external genitalia that resemble that of males, and close their vaginal orifice after every estrus, and female spotted hyenas lack an external vaginal orifice and develop a pseudoscrotum and a large pseudopenis through which they urinate, mate, and give birth. We review current knowledge about several significant aspects of the biology and evolution of these females, including () their specific study methods; () their unique anatomical features, and how these peculiarities influence certain physiological functions; and () the role that steroid hormones as well as genetic and environmental factors may have in urogenital system development, aggressive behavior, and social dominance. Nevertheless, both mole and hyena females are exceptionally efficient mothers, so their peculiar genitalia should not call into question their femininity.
Topics: Male; Female; Animals; Hyaenidae; Moles; Steroids; Genitalia; Biology
PubMed: 36130099
DOI: 10.1146/annurev-animal-050622-043424 -
Biomolecules Apr 2023Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex... (Review)
Review
Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex development (DSD). To date, pathogenic variants of three nuclear receptor genes (, , and ) have been reported to cause DSD via atypical testicular development. In this review article, we describe the clinical significance of the variants as the cause of DSD and introduce novel findings from recent studies. variants are associated with 46,XY DSD and 46,XX testicular/ovotesticular DSD. Notably, both 46,XX DSD and 46,XY DSD caused by the variants show remarkable phenotypic variability, to which digenic/oligogenic inheritances potentially contribute. Additionally, we discuss the roles of and in the etiology of DSD. acts as an anti-testicular gene. Duplications containing result in 46,XY DSD, whereas deletions encompassing can underlie 46,XX testicular/ovotesticular DSD. has recently been reported as a causative gene for 46,XX testicular/ovotesticular DSD and possibly for 46,XY DSD, although the role of in gonadal development is unclear. The knowledge about these three nuclear receptors provides novel insights into the molecular networks involved in the gonadal development in human fetuses.
Topics: Humans; Male; Disorder of Sex Development, 46,XY; Mutation; Ovotesticular Disorders of Sex Development; Phenotype; Sexual Development; Testis; Receptors, Cytoplasmic and Nuclear
PubMed: 37189438
DOI: 10.3390/biom13040691 -
International Journal of Women's... Oct 2023Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal,... (Review)
Review
BACKGROUND
Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex.
OBJECTIVE
Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD.
DATA SOURCES
Published articles including case series and case reports on PubMed.
STUDY SELECTIONS
Selection was conducted by examining existing literature with a team of multidisciplinary specialists.
METHODS
Narrative review.
LIMITATIONS
This article was not conducted as a systematic review.
RESULTS
In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common.
CONCLUSION
Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.
PubMed: 37671254
DOI: 10.1097/JW9.0000000000000106 -
Differentiation; Research in Biological... 2023Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human...
Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human testicular tissue are well defined by the presence of seminiferous cords or tubules containing TSPY-positive germ cells and Sox9-positive Sertoli cells surrounded by interstitial tissue containing cytochrome P450-positive Leydig cells and smooth muscle α-actin-positive peritubular myoid cells. The histological characteristics of the ovary can be defined by germ cell nests and the development of follicles. In contrast to the testis, the ovary has a paucity of defined specific protein markers, with the granulosa cell marker FOXL2 being the most widely used. In practice, defining the ovarian component of the ovotestis can be quite difficult. We developed a model of human ovotesticular syndrome by combining fetal human testis and ovary in a xenograft model. Ovotesticular xenografts were grown under the renal capsules of gonadectomized athymic nude mice for 6-32 weeks along with age matched control grafts of fetal testis and ovary. Forty ovotesticular xenografts and their controls were analyzed by histology, immunohistochemistry, and fluorescent in situ hybridization to determine the protein expression and karyotype of the cells within the grafts. The ovotesticular xenografts exhibited recognizable testicular and ovarian tissue based on testis-specific and ovary-specific markers defined above. The xenografts simulated a bipolar ovotestis in which the testicular and ovarian elements retain their separate histological characteristics and are separated by a well-defined border. This contrasts with the compartmentalized ovotestis previously described in the literature where the testicular tissue is surrounded by ovarian tissue or a mixed histology where testicular and ovarian tissues are interspersed throughout the gonad. In conclusion, we have characterized a human model of ovotestis which will allow a deeper understanding of ovotestis development in humans and facilitate a more accurate diagnosis of the ovotesticular syndrome.
Topics: Female; Animals; Mice; Humans; Male; Testis; Mice, Nude; In Situ Hybridization, Fluorescence; Gonads; Ovary; Ovotesticular Disorders of Sex Development
PubMed: 35164980
DOI: 10.1016/j.diff.2021.12.003 -
Experimental Parasitology Jun 2020Infection with trematodes produces physiological and behavioural changes in intermediate snail hosts. One response to infection is parasitic castration, in which energy...
Infection with trematodes produces physiological and behavioural changes in intermediate snail hosts. One response to infection is parasitic castration, in which energy required for reproduction of the host is thought to be redirected to promote development and multiplication of the parasite. This study investigated some reproductive and biochemical parameters in the nervous (CNS) and ovotestis (OT) tissues of Biomphalaria alexandrina during the course of Schistosoma mansoni infection. Antioxidant and oxidative stress parameters including catalase (CAT), nitric oxide (NO) and lipid peroxidation (MDA) were measured. Levels of steroid hormones, including testosterone, progesterone and estradiol, were also assessed. Finally, flow cytometry was used to compare measures of apoptosis between control snails and those shedding cercariae by examining mitochondrial membrane potential with the stain 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) and poly(ADP-ribose) polymerase (PARP). Infection with S. mansoni caused a 47.7% reduction in the net reproductive rate (R) of B. alexandrina. CAT activity was increased in the CNS at 21 days post infection (dpi) but by 28 dpi it was reduced below control values. Also, CAT activity increased significantly in the OT at 14, 21 and 28 dpi. In CNS tissues, NO levels were reduced at 7 dpi, increased at 14 and 21 dpi, and reduced again at 28 dpi. The overall level of lipid peroxidation gradually increased during the course of infection to reach its highest levels at 28 dpi. Steroid hormone measurements showed that concentrations of testosterone and estradiol were reduced in the CNS tissues at 28 dpi, while those of progesterone were slightly increased in the CNS and OT tissues. The percentage of cells that positively stained with JC-1was significantly increased in CNS and OT tissues of infected snails while the percentage of cells positively stained with PARP was decreased compared to controls. Together, these findings indicate that infection initiates diverse biochemical and hormonal changes leading to loss of cells responsible for egg laying and reproduction in B. alexandrina.
Topics: Animals; Biomphalaria; Cercaria; Gonads; Host-Parasite Interactions; Nervous System; Schistosoma mansoni
PubMed: 32224062
DOI: 10.1016/j.exppara.2020.107887