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Animals : An Open Access Journal From... Sep 2020Impaired fertility associated with disorders of sex development (DSDs) due to genetic causes in dogs are more and more frequently reported. Affected dogs are usually of...
Impaired fertility associated with disorders of sex development (DSDs) due to genetic causes in dogs are more and more frequently reported. Affected dogs are usually of specific breeds thus representing a cause of economic losses for breeders. The aim of this research is to report the clinical, cytogenetic and molecular genetic findings of four XX -negative DSD dog cases. All the subjects showed a female aspect and the presence of an enlarged clitoris with a penis bone. Morphopathological analyses performed in three of the four cases showed the presence of testes in two cases and ovotestis in another. Conventional and R-banded cytogenetic techniques were applied showing that no chromosome abnormalities were involved in these DSDs. CGH arrays show the presence of 11 copy number variations (CNVs), one of which is a duplication of 458 Kb comprising the genomic region between base 17,503,928 and base 17,962,221 of chromosome 9 (CanFam3 genome assembly). This CNV, confirmed also by qPCR, includes the promoter region of gene and could explain the observed phenotype.
PubMed: 32947906
DOI: 10.3390/ani10091667 -
Frontiers in Genetics 2020Yellowfin seabream (), a protandrous hermaphroditic fish, is a good model for studying the mechanism of sex reversal. However, limited knowledge is known about the...
Yellowfin seabream (), a protandrous hermaphroditic fish, is a good model for studying the mechanism of sex reversal. However, limited knowledge is known about the genetic information related to reproduction and sex differentiation in this species. Here, we performed transcriptome sequencing analysis of the testis, ovotestis, and ovary to identify sex-related genes in yellowfin seabream. The results assembled 71,765 unigenes in which 16,126 and 17,560 unigenes were differentially expressed in the ovotestis and ovary compared to the testis, respectively. The most differentially expressed gene (DEG)-enriched Kyoto Encyclopedia of Genes and Genomes and GO pathways were closely associated with the synthesis of sex steroid hormones. Functional analyses identified 55 important sex-related DEGs, including 32 testis-biased DEGs (, , and , etc.), 20 ovary-biased DEGs (, , and , etc.), and 3 ovotestis-biased DEGs (, , and ). Furthermore, the testis-specific expression of and the brain-pituitary-ovary axis expression of were characterized, suggesting that they might play important roles in sex differentiation in yellowfin seabream. Our present work provided an important molecular basis for elucidating the mechanisms underlying sexual transition and reproductional regulation in yellowfin seabream.
PubMed: 32765585
DOI: 10.3389/fgene.2020.00709 -
Journal of Reproduction & Infertility 2020Klinefelter syndrome (KS) mosaicism 46,XX/47,XXY is an extremely rare disorder of sex development characterized by the presence of both ovarian and testicular tissues in...
BACKGROUND
Klinefelter syndrome (KS) mosaicism 46,XX/47,XXY is an extremely rare disorder of sex development characterized by the presence of both ovarian and testicular tissues in the same individual. Both elements can be present in the same gonad (ovotestis) or separately in the same individual or as a unilateral ovotestis and the other side with testis or ovary. A mosaic with 46,XY would present with problems related to male infertility and in general, testicular insufficiency, but with a 46,XX mosaic, it is a completely rare presentation. As adolescents, these boys may experience severe emotional and behavioral issues; it is up to the parents to identify these conditions early and get them physician evaluated for possible abnormalities so that they can get the benefit of treatment.
CASE PRESENTATION
A case of a rare disorder of sexual differentiation with a mosaic 46,XX/47,XXY in a KS individual is reported for whom karyotyping and SRY-FISH work-up was done.
CONCLUSION
Early cytogenetic testing is essential to identify these individuals and testosterone replacement therapy and breast reduction for case management are helpful. Assisted reproductive technology (ART) may assist these individuals father children in some cases.
PubMed: 32685420
DOI: No ID Found -
Journal of Pediatric Urology Oct 2020Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains... (Observational Study)
Observational Study
Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains controversy around the traditionally binary concept of sex, most patients with DSD are reared either male or female depending on their genetic sex, gonadal sex, genital phenotype and status of their internal genital tract. This study uses prospective data from 12 institutions across the United States that specialize in DSD care. We focused on patients raised female. Eligible patients had moderate to severe genital atypia (defined as Prader score >2), were ≤2 years of age at entry, and had no prior genitoplasty. The aim of this study is to describe early post operative complications for young patients undergoing modern approaches to feminizing genitoplasty. Of the 91 participants in the cohort, 57 (62%) were reared female. The majority had congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (n = 52), 1 had ovo-testicular syndrome, 2 had mixed gonadal dysgenesis and 2 had partial androgen insensitivity syndrome (PAIS). Of the 50 participants who received early genitoplasty, 43 (86%) had follow-up at 6-12 months post-surgery. Thirty-two participants (64%) received a clitoroplasty, 31 (62%) partial urogenital mobilization and 4 (8%) total urogenital sinus mobilization. Eighteen percent (9/50) experienced post-surgical complications with 7 (14%) being rated as Clavien-Dindo grade III. Both parents and surgeons reported improved satisfaction with genital appearance of participants following surgery compared to baseline. This information on post-operative complications associated with contemporary approaches to feminizing genitoplasty performed in young children will help guide families when making decisions about whether or not to proceed with surgery for female patients with moderate to severe genital atypia.
Topics: Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Cohort Studies; Disorders of Sex Development; Female; Genitalia; Humans; Male; Prospective Studies; Urogenital Surgical Procedures
PubMed: 32624410
DOI: 10.1016/j.jpurol.2020.05.166 -
Proceedings of the National Academy of... Jun 2020Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development...
Sex determination in mammals is governed by antagonistic interactions of two genetic pathways, imbalance in which may lead to disorders/differences of sex development (DSD) in human. Among 46,XX individuals with testicular DSD (TDSD) or ovotesticular DSD (OTDSD), testicular tissue is present in the gonad. Although the testis-determining gene is present in many cases, the etiology is unknown in most -negative patients. We performed exome sequencing on 78 individuals with 46,XX TDSD/OTDSD of unknown genetic etiology and identified seven (8.97%) with heterozygous variants affecting the fourth zinc finger (ZF4) of Wilms' tumor 1 (WT1) (p.Ser478Thrfs*17, p.Pro481Leufs*15, p.Lys491Glu, p.Arg495Gln [x3], p.Arg495Gly). The variants were de novo in six families ( = 4.4 × 10), and the incidence of WT1 variants in 46,XX DSD is enriched compared to control populations ( < 1.8 × 10). The introduction of ZF4 mutants into a human granulosa cell line resulted in up-regulation of endogenous Sertoli cell transcripts and XX mice display masculinization of the fetal gonads. The phenotype could be explained by the ability of the mutated proteins to physically interact with and sequester a key pro-ovary factor β-CATENIN, which may lead to up-regulation of testis-specific pathway. Our data show that unlike previous association of WT1 and 46,XY DSD, ZF4 variants of WT1 are a relatively common cause of 46,XX TDSD/OTDSD. This expands the spectrum of phenotypes associated with WT1 variants and shows that the WT1 protein affecting ZF4 can function as a protestis factor in an XX chromosomal context.
Topics: 46, XX Testicular Disorders of Sex Development; Animals; Child, Preschool; Female; Humans; Infant; Male; Mice; Ovary; Testis; WT1 Proteins; Zinc Fingers; beta Catenin
PubMed: 32493750
DOI: 10.1073/pnas.1921676117 -
Medicine May 2020True hermaphroditism is a rare and usually sporadic disorder. It is defined by the presence of both ovarian and testicular tissues together as ovotestis.
INTRODUCTION
True hermaphroditism is a rare and usually sporadic disorder. It is defined by the presence of both ovarian and testicular tissues together as ovotestis.
PATIENT CONCERNS
In this study, we reported a rare true hermaphroditism case with dysgerminoma. A 49-year-old woman developed masses in both inguinal regions for 30 years. Recently 3 months, the patient found that the size of mass in her left inguinal region was significantly increased.
DIAGNOSIS
After surgical resection, the results of immunohistochemical examination in left mass revealed a dysgerminoma with positive expression of placental alkaline phosphatase and octamer-binding transcription factor 3/4, and right mass was a cryptorchidism. Chromosomal analysis revealed the karyotype 46, XY. Combined immunohistochemical and karyotype analysis, a diagnosis of true hermaphroditism with dysgerminoma was made.
INTERVENTIONS
Radiotherapy combined with chemotherapy after tumor resection was used to improve her prognosis. Hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate were used to maintain her female characteristics.
OUTCOMES
The patient underwent hormonal replacement and has been well for 6 months.
CONCLUSION
The positive expression of placental alkaline phosphatase and octamer-binding transcription factor 3/4 could be 2 diagnosis markers of dysgerminoma. Surgery combined with radiotherapy and chemotherapy could improve the prognosis of dysgerminoma. Moreover, hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate was very helpful to maintain the female characteristic of patients with true hermaphroditism.
Topics: Diagnosis, Differential; Dysgerminoma; Female; Humans; Male; Middle Aged; Ovarian Neoplasms; Ovotesticular Disorders of Sex Development
PubMed: 32481455
DOI: 10.1097/MD.0000000000020472 -
Cells Apr 2020The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common...
The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when and are both mutated. We show that the XX gonad mutant for or for both and develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a mutation. deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of or , indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.
Topics: Animals; Cell Differentiation; Female; Gene Expression Regulation, Developmental; Gonads; Granulosa Cells; Male; Mice, Knockout; Ovary; SOX9 Transcription Factor; Testis; Wnt4 Protein
PubMed: 32365547
DOI: 10.3390/cells9051103 -
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 -
Endokrynologia Polska 2020Patients with disorders/differences of sex differentiation/development (DSD) are exposed to physical and mental suffering. The aim of the study was to assess the...
INTRODUCTION
Patients with disorders/differences of sex differentiation/development (DSD) are exposed to physical and mental suffering. The aim of the study was to assess the following: the mental health status and the risk of mental problems in adult DSD patients, their dependence on therapeutic procedures, and to identify groups of disorders that require particular psychological support.
MATERIAL AND METHODS
The study involved 59 patients with DSD (gonadal dysgenesis - GD, androgen insensitivity syndrome - AIS, 5-alpha reductase deficiency, ovotestis), and with the Y chromosome in the karyotype, aged 16-65 years. All completed the General Health Questionnaire (GHQ-28) for the assessment of their mental health status. Raw results were converted into sten scores using norms for the Polish adult population to assess the risk of mental problems.
RESULTS
A high risk of mental problems was identified in 24% of individuals (26% men, 21% women). Women, when compared with men, displayed a significantly higher mean level of anxiety and insomnia (7.3 vs. 4.6 scores) and somatic symptoms (7.4 vs. 5.5), and worse general mental health status (25.6 vs. 18.8). The most disturbing symptoms were observed among patients with complete and partial AIS, and complete GD (general mental health status: 39.5, 24.3, and 24.2, respectively), women lacking a vagina (27.2), and without an enlarged clitoris (27.5). Patients after genital surgery had significantly fewer somatic symptoms (5.4 vs. 7.8; p < 0.05) and better general mental health status in comparison to those without surgery (20.1 vs. 24.9; p < 0.05). No significant differences were observed between patients using hormone replacement therapy and those who were not.
CONCLUSIONS
The individuals with DSD and Y chromosome in the karyotype have increased risk of developing mental problems in comparison to the general Polish population. The risk factors seem to be as follows: female gender, the lack of a vagina, the lack of virilisation (no enlarged clitoris), and no genital operations performed. In some cases, sex hormone replacement therapy may be also the risk of mental problems. Particularly vulnerable groups are CAIS, PAIS, and CGD. The psychological support and an individual approach to particular needs of these patients is necessary.
Topics: Adaptation, Psychological; Adolescent; Adult; Chromosomes, Human, Y; Disorders of Sex Development; Female; Humans; Male; Mental Disorders; Mental Health; Middle Aged; Poland; Quality of Life; Sex Differentiation; Young Adult
PubMed: 32129466
DOI: 10.5603/EP.a2020.0005 -
Scientific Reports Jan 2020The Northern spot shrimp, Pandalus platyceros, a protandric hermaphrodite of commercial importance in North America, is the primary target species for shrimp fisheries...
The Northern spot shrimp, Pandalus platyceros, a protandric hermaphrodite of commercial importance in North America, is the primary target species for shrimp fisheries within Southeast Alaska. Fishery data obtained from the Alaska Department of Fish and Game indicate that spot shrimp populations have been declining significantly over the past 25 years. We collected spot shrimps in Southeast Alaska and measured reproductive-related morphological, gonadal and molecular changes during the entire life history. The appendix masculina, a major sexual morphological indicator, is indicative of the reproductive phase of the animal, lengthening during maturation from juvenile to the male phase and then gradually shortening throughout the transitional stages until its complete disappearance upon transformation to a female. This morphological change occurs in parallel with the degeneration of testicular tissue in the ovotestis and enhanced ovarian vitellogenesis. Moreover, we obtained the entire mRNA sequence of the yolk protein precursor, vitellogenin, and monitored its transcript levels throughout the entire shrimp life-cycle. Vitellogenin transcript levels in the hepatopancreas increased in the early transitional stage until reaching a peak prior to extruding eggs. Such transcriptomic analyses, coupled with a comprehensive description of the gonad, external sex characters and timing of the reproductive life history of spot shrimps contribute to a better understanding of the hermaphroditic reproduction process in the cold Southeast Alaskan waters. This knowledge can contribute to a revision of current conservation efforts to maintain wild populations sustainable for both commercial and ecological considerations.
Topics: Alaska; Animals; Arthropod Proteins; Conservation of Energy Resources; Fisheries; Pandalidae; RNA, Messenger; Sequence Analysis, RNA; Transcriptome
PubMed: 31992795
DOI: 10.1038/s41598-020-58262-6