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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 -
Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterus albus.Biology of Sex Differences Oct 2023Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism...
BACKGROUND
Monopterus albus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.
METHODS
We produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.
RESULTS
This effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.
CONCLUSIONS
This study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M. albus, which will also enrich the sex differentiation mechanism of teleosts.
Topics: Male; Animals; Female; RNA, Long Noncoding; Gonads; Ovary; Testis; Sex Differentiation; Smegmamorpha
PubMed: 37880697
DOI: 10.1186/s13293-023-00559-y -
Frontiers in Endocrinology 2024Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by... (Review)
Review
Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by exposure to exogenous androgens. The most common cause of 46,XX disorders/differences in sex development (DSD) is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, comprising >90% of 46,XX DSD cases. Deficiencies of 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, and P450-oxidoreductase (POR) are rare types of CAH, resulting in 46,XX DSD. In all CAH forms, patients have normal ovarian development. The molecular genetic causes of 46,XX DSD, besides CAH, are uncommon. These etiologies include primary glucocorticoid resistance (PGCR) and aromatase deficiency with normal ovarian development. Additionally, 46,XX gonads can differentiate into testes, causing 46,XX testicular (T) DSD or a coexistence of ovarian and testicular tissue, defined as 46,XX ovotesticular (OT)-DSD. PGCR is caused by inactivating variants in , resulting in glucocorticoid insensitivity and the signs of mineralocorticoid and androgen excess. Pathogenic variants in the gene lead to aromatase deficiency, causing androgen excess. Many genes are involved in the mechanisms of gonadal development, and genes associated with 46,XX T/OT-DSD include translocations of the ; copy number variants in , , , , , and , and sequence variants in , , , , , , and . Progress in cytogenetic and molecular genetic techniques has significantly improved our understanding of the etiology of non-CAH 46,XX DSD. Nonetheless, uncertainties about gonadal function and gender outcomes may make the management of these conditions challenging. This review explores the intricate landscape of diagnosing and managing these conditions, shedding light on the unique aspects that distinguish them from other types of DSD.
Topics: Humans; Adrenal Hyperplasia, Congenital; 46, XX Disorders of Sex Development; Female; Male; Disorders of Sex Development
PubMed: 38812815
DOI: 10.3389/fendo.2024.1354759 -
Frontiers in Endocrinology 2024In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of... (Review)
Review
In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of to the X chromosome or an autosome. In the absence of , other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.
Topics: Humans; Male; Testis; Animals; Female; 46, XX Disorders of Sex Development; Sex Differentiation; Disorders of Sex Development
PubMed: 38721146
DOI: 10.3389/fendo.2024.1385901 -
BMC Women's Health Oct 2023Ovotestis is a rare cause of sexual ambiguity characterized by the presence in a patient of both testicular and ovarian tissue, leading to the development of both male... (Review)
Review
INTRODUCTION
Ovotestis is a rare cause of sexual ambiguity characterized by the presence in a patient of both testicular and ovarian tissue, leading to the development of both male and female structures. We report a case of ovotestis diagnosed in an adolescent, with a review of the literature.
CASE REPORT
A 15-year-old patient presented with a right scrotal swelling associated with gynecomastia. Histology showed a juxtaposition of ovarian stroma with ovarian follicle and seminiferous tubules. Karyotype revealed a male subject (XY). We have therefore retained the diagnosis of ovotesticular disorders of sex development.
CONCLUSION
Ovotestis is a rare finding, heterogeneous in its genetic etiology and clinical presentation. While many patients are diagnosed during infancy or childhood, we presented a case diagnosed in a 15-year-old adolescent.
Topics: Adolescent; Female; Humans; Male; Karyotype; Ovary; Ovotesticular Disorders of Sex Development
PubMed: 37875919
DOI: 10.1186/s12905-023-02698-1 -
Frontiers in Toxicology 2023Japanese medaka () is an acceptable small laboratory fish model for the evaluation and assessment of endocrine-disrupting chemicals (EDCs) found in the environment. In...
Japanese medaka () is an acceptable small laboratory fish model for the evaluation and assessment of endocrine-disrupting chemicals (EDCs) found in the environment. In this research, we used this fish as a potential tool for the identification of EDCs that have a significant impact on human health. We conducted an electronic search in PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar (https://scholar.google.com/) using the search terms, Japanese medaka, , and endocrine disruptions, and sorted 205 articles consisting of 128 chemicals that showed potential effects on estrogen-androgen-thyroid-steroidogenesis (EATS) pathways of Japanese medaka. From these chemicals, 14 compounds, namely, 17β-estradiol (E2), ethinylestradiol (EE2), tamoxifen (TAM), 11-ketotestosterone (11-KT), 17β-trenbolone (TRB), flutamide (FLU), vinclozolin (VIN), triiodothyronine (T3), perfluorooctanoic acid (PFOA), tetrabromobisphenol A (TBBPA), terephthalic acid (TPA), trifloxystrobin (TRF), ketoconazole (KTC), and prochloraz (PCZ), were selected as references and used for the identification of apical endpoints within the EATS modalities. Among these endpoints, during classification, priorities are given to sex reversal (masculinization of females and feminization of males), gonad histology (testis-ova or ovotestis), secondary sex characteristics (anal fin papillae of males), plasma and liver vitellogenin (VTG) contents in males, swim bladder inflation during larval development, hepatic vitellogenin () and choriogenin () genes in the liver of males, and several genes, including estrogen-androgen-thyroid receptors in the hypothalamus-pituitary-gonad/thyroid axis (HPG/T). After reviewing 205 articles, we identified 108 (52.68%), 46 (22.43%), 19 (9.26%), 22 (17.18%), and 26 (12.68%) papers that represented studies on estrogen endocrine disruptors (EEDs), androgen endocrine disruptors (AEDs), thyroid endocrine disruptors (TEDs), and/or steroidogenesis modulators (MOS), respectively. Most importantly, among 128 EDCs, 32 (25%), 22 (17.18%), 15 (11.8%), and 14 (10.93%) chemicals were classified as EEDs, AEDs, TEDs, and MOS, respectively. We also identified 43 (33.59%) chemicals as high-priority candidates for tier 2 tests, and 13 chemicals (10.15%) show enough potential to be considered EDCs without any further tier-based studies. Although our literature search was unable to identify the EATS targets of 45 chemicals (35%) studied in 60 (29.26%) of the 205 articles, our approach has sufficient potential to further move the laboratory-based research data on Japanese medaka for applications in regulatory risk assessments in humans.
PubMed: 38090358
DOI: 10.3389/ftox.2023.1272368 -
Cureus Jun 2023A case is reported herein of a true hermaphrodite (TH) with an ovotestis, a uterus, a vagina, and an underdeveloped phallus. The patient was raised by his parents as a...
A case is reported herein of a true hermaphrodite (TH) with an ovotestis, a uterus, a vagina, and an underdeveloped phallus. The patient was raised by his parents as a male, based on the presence of a phallus with ambiguous genitalia. He started experiencing breast enlargement at the age of 14 and menarche by the age of 17. He was reviewed using ultrasound, magnetic resonance imaging of the abdomen, and karyotyping, and the reports showed evidence of Mullerian structures and 46 XX karyotyping. Based on the preferences of the patient and his parents and their psychological outlook toward the male gender, a total mastectomy, hysterectomy, bilateral gonadectomy, and total vaginectomy were performed. This was followed by reconstruction of the male genitalia and supplemented with male hormone replacement therapy. Accordingly, a TH was assigned a male gender.
PubMed: 37425607
DOI: 10.7759/cureus.40104 -
Differentiation; Research in Biological... 2024
Topics: Humans; Ovotesticular Disorders of Sex Development; Gonads
PubMed: 38000942
DOI: 10.1016/j.diff.2023.11.002 -
Biology Mar 2024This study aimed to develop a cryopreservation system for the reproductive organs of (oriental snail) to support the conservation of their species. The reproductive...
This study aimed to develop a cryopreservation system for the reproductive organs of (oriental snail) to support the conservation of their species. The reproductive glands of are divided into numerous acini by acinar boundaries. Within each acinus, the presence of spermatogonia, spermatocytes, spermatids, and sperm were observed, indicating various stages of sperm development. The spermatocytes were irregular in shape and possessed large nuclei. Spermatids, on the other hand, were predominantly located within the lumen of the tissue and exhibited densely packed nuclei. Furthermore, sperm with tails attached were observed within the tissue. In order to preserve the oriental snail species, we utilized the vitrification method to freeze the reproductive organs. Comparing the two methods, it was observed that cryopreservation of ovotestis using 2% alginate encapsulation exhibited superior viability following thawing, surpassing the viability achieved with the non-encapsulated approach. In this study, the establishment of a cryopreservation system for the reproductive organs of the oriental snail not only contributes to the genetic conservation of the endangered snail species but also plays a role in maintaining genetic resources and diversity.
PubMed: 38666817
DOI: 10.3390/biology13040205 -
Scientific Reports Jan 2024Vitellogenesis is the most important process in animal reproduction, in which yolk proteins play a vital role. Among multiple yolk protein precursors, vitellogenin (Vtg)...
Vitellogenesis is the most important process in animal reproduction, in which yolk proteins play a vital role. Among multiple yolk protein precursors, vitellogenin (Vtg) is a well-known major yolk protein (MYP) in most oviparous animals. However, the nature of MYP in the freshwater gastropod snail Biomphalaria glabrata remains elusive. In the current study, we applied bioinformatics, tissue-specific transcriptomics, ovotestis-targeted proteomics, and phylogenetics to investigate the large lipid transfer protein (LLTP) superfamily and ferritin-like family in B. glabrata. Four members of LLTP superfamily (BgVtg1, BgVtg2, BgApo1, and BgApo2), one yolk ferritin (Bg yolk ferritin), and four soma ferritins (Bg ferritin 1, 2, 3, and 4) were identified in B. glabrata genome. The proteomic analysis demonstrated that, among the putative yolk proteins, BgVtg1 was the yolk protein appearing in the highest amount in the ovotestis, followed by Bg yolk ferritin. RNAseq profile showed that the leading synthesis sites of BgVtg1 and Bg yolk ferritin are in the ovotestis (presumably follicle cells) and digestive gland, respectively. Phylogenetic analysis indicated that BgVtg1 is well clustered with Vtgs of other vertebrates and invertebrates. We conclude that, vitellogenin (BgVtg1), not yolk ferritin (Bg yolk ferritin), is the major yolk protein precursor in the schistosomiasis vector snail B. glabrata.
Topics: Animals; Biomphalaria; Vitellogenins; Multiomics; Phylogeny; Proteomics; Egg Proteins; Schistosomiasis; Ferritins; Schistosoma mansoni
PubMed: 38245605
DOI: 10.1038/s41598-024-52392-x