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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 -
Cureus Dec 2020Ovotesticular disorder or true hermaphroditism is defined as the presence of both ovarian and testicular tissues in the same individual irrespective of the patient's...
Ovotesticular disorder or true hermaphroditism is defined as the presence of both ovarian and testicular tissues in the same individual irrespective of the patient's karyotype. Ovotesticular disorder represents 5% of disorders of sex development. Cases of true hermaphroditism must be treated like men or women based on their age, external genitalia and the orientation of the patient. Here we report a case of true hermaphroditism which was diagnosed with seminoma on histopathological examination. The patient underwent orchiectomy, followed by two cycles of chemotherapy.
PubMed: 33489542
DOI: 10.7759/cureus.12130 -
The Journal of Comparative Neurology Jun 2021Freshwater snails of the genus Biomphalaria serve as obligatory hosts for the digenetic trematode Schistosoma mansoni, the causative agent for the most widespread form...
Freshwater snails of the genus Biomphalaria serve as obligatory hosts for the digenetic trematode Schistosoma mansoni, the causative agent for the most widespread form of intestinal schistosomiasis. Within Biomphalaria, S. mansoni larvae multiply and transform into the cercariae form that can infect humans. Trematode development and proliferation is thought to be facilitated by modifications of host behavior and physiological processes, including a reduction of reproduction known as "parasitic castration." As neuropeptides participate in the control of reproduction across phylogeny, a neural transcriptomics approach was undertaken to identify peptides that could regulate Biomphalaria reproductive physiology. The present study identified a transcript in Biomphalaria alexandrina that encodes a peptide belonging to the gonadotropin-releasing hormone (GnRH) superfamily. The precursor and the predicted mature peptide, pQIHFTPDWGNN-NH (designated Biom-GnRH), share features with peptides identified in other molluscan species, including panpulmonates, opisthobranchs, and cephalopods. An antibody generated against Biom-GnRH labeled neurons in the cerebral, pedal, and visceral ganglia of Biomphalaria glabrata. GnRH-like immunoreactive fiber systems projected to all central ganglia. In the periphery, immunoreactive material was detected in the ovotestis, oviduct, albumen gland, and nidamental gland. As these structures serve crucial roles in the production, transport, nourishment, and encapsulation of eggs, disruption of the GnRH system of Biomphalaria could contribute to reduced reproductive activity in infected snails.
Topics: Amino Acid Sequence; Animals; Biomphalaria; Gonadotropin-Releasing Hormone; Host-Parasite Interactions; Neuropeptides; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 33368267
DOI: 10.1002/cne.25099 -
Heliyon Dec 2020The present study focused on evaluating the effects of oral administration of three different concentrations of Yasmin® combined contraceptive pills (estrogen and...
The present study focused on evaluating the effects of oral administration of three different concentrations of Yasmin® combined contraceptive pills (estrogen and progesterone) on reproductive hormones levels, histology of the ovotestis and rate of oviposition of for two months using baits technique. The levels of anti-müllerian hormone (AMH), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2), Progesterone(PRG), Thyroid-stimulating hormone (TSH) and Testesterone (T) of treated snails were decreased with increasing the drug concentrations by percentages of -83.3%, -78.9%, - 59.6%,- 98.3 %, - 79.6 %, - 86.7% and 8.2%, respectively. Prolactin (PRL) level was significantly increased (86.9%) compared to control snails after 8 weeks of exposure. Histological investigations on the hermaphrodite glands of snails treated with 909 μg/gm. showed glandular hyperplasia, sloughing of germinal epithelium, acini sizes reduction, suppression of follicular growths, decreased luteinization and vasodilation. Male acini revealed histolytic of spermatogonia and mature sperms. The lowest concentration (303 μg/gm.) caused gradual decrease of the total egg counts that reach 50% at the 8 week of treatment. Higher doses (606 and 909 μg/gm.) resulted in dramatic dwindling of egg numbers and inspiring complete egg cessation at the 7 and 3 weeks of treatments, respectively. The applications of combined contraceptive drugs as baits give promising results for controlling high population densities of snails at Sharkia Governorate, Egypt.
PubMed: 33319095
DOI: 10.1016/j.heliyon.2020.e05630 -
Cell & Bioscience Nov 2020Both testis and ovary can be produced sequentially in an individual with the same genome when sex reversal occurs in the teleost Monopterus albus, and epigenetic...
BACKGROUND
Both testis and ovary can be produced sequentially in an individual with the same genome when sex reversal occurs in the teleost Monopterus albus, and epigenetic modification is supposed to be involved in gonadal differentiation. However, DNA methylation regulation mechanism underlying the gonadal differentiation remains unclear.
RESULTS
Here, we used liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to simultaneously determine endogenous levels of both 5-methyl-2'-deoxycytidine (mdC) and 5-hydroxymethyl-2'-deoxycytidine (hmdC) during gonadal differentiation. Overall DNA methylation level was upregulated from ovary to testis via ovotestis. As a de novo methylase, dnmt3aa expression was also upregulated in the process. Notably, we determined transcription factor Foxa1 for dnmt3aa gene expression. Site-specific mutations and chromatin immunoprecipitation showed that Foxa1 can bind to and activate the dnmt3aa promoter. Furthermore, DNA methylation levels of key genes foxl2 (forkhead box L2) and cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a) in regulation of female hormone synthesis were consistently upregulated during gonadal differentiation.
CONCLUSIONS
These data suggested that dynamic change of DNA methylation modification is associated with gonadal differentiation.
PubMed: 33292595
DOI: 10.1186/s13578-020-00490-4 -
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 -
The Indian Journal of Medical Research Nov 2020
Topics: Humans; Karyotyping; Ovotesticular Disorders of Sex Development
PubMed: 35345152
DOI: 10.4103/ijmr.IJMR_2178_19 -
Indian Journal of Endocrinology and... 2020Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in...
BACKGROUND
Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in treating any coexisting hormone deficiencies and can help with anticipating any other immediate or long-term health concerns.
OBJECTIVE
To study the clinical and biochemical profile of patients with 46 XY DSD along with androgen receptor (AR) gene mutation status in selected group of patients.
METHODS
A cross-sectional study was conducted after enrolling the eligible DSD patients. Thorough elicitation of history and detailed clinical examination was done. Assays for luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, androstenedione, AMH & Inhibin B (where indicated), and human chorionic gonadotropin stimulation were done as per protocol.
RESULTS
In total, 48 patients were included in the study. Ambiguous genitalia (58.3%) followed by hypospadias (33.3%) were common presentation. Androgen biosynthetic defect were the most commonly encountered diagnosis followed by androgen insensitivity syndrome (AIS). Swyer syndrome was diagnosed in 4.2% of cases; partial gonadal dysgenesis, ovotesticular DSD, and vanishing testis syndrome contributed to 2% of cases each. Eight cases (16.7%) who presented with isolated proximal and midshaft hypospadias for whom no diagnosis was found were categorized in the "etiology unclear" group. AR gene mutation analysis designed against specific exons did not yield any results.
CONCLUSION
46 XY DSD is a heterogeneous group of patients with a varying age of presentation and a diverse clinical profile. Most patients are reared as males and maintained the same gender identity except in isolated cases. Diagnosis of AIS remains a clinical challenge as a definite hormonal criterion does not exist and genetic mutations in AR gene may be negative. Flanking region sequencing, whole genome sequencing, and promoter region sequencing may reveal pathogenic variants. Variations in other genes regulating AR pathway may also be candidates to be studied.
PubMed: 33088761
DOI: 10.4103/ijem.IJEM_98_20 -
Medicine Oct 2020Ovotesticular disorder of sex development (DSD), previously known as true hermaphroditism, is a disorder in which individuals have both testicular and ovarian tissues....
RATIONALE
Ovotesticular disorder of sex development (DSD), previously known as true hermaphroditism, is a disorder in which individuals have both testicular and ovarian tissues. Instances of tumors arising in the gonads of individuals with 46,XX ovotesticular DSD are uncommon.
PATIENT CONCERNS
We report a case of a 36-year-old phenotypical male with a chief complaint of an abdominal mass for 3 months. He reported normal erections and regular menses. Computerized tomography showed a large tumor measuring 15 × 10 cm in size, a uterus, and a cystic ovary.
DIAGNOSIS
46, XX ovotesticular DSD with seminoma.
INTERVENTIONS
The patient was treated with neochemotherapy (etoposide and cisplatin), surgery, chemotherapy, and testosterone replacement.
OUTCOMES
At the 13-month follow-up, the patient reported satisfactory erections, and no evidence of disease was found.
CONCLUSION
Cases of 46,XX ovotesticular DSD with seminoma are uncommon. Our case reveals the importance of surgery combined with neochemotherapy, chemotherapy, and testosterone replacement in these patients to improve the prognosis.
Topics: Adult; Humans; Male; Ovotesticular Disorders of Sex Development; Seminoma; Testicular Neoplasms
PubMed: 33019456
DOI: 10.1097/MD.0000000000022530 -
Frontiers in Endocrinology 2020Disorders of sex development (DSD) are conditions where genetic, gonadal, and/or internal/external genital sexes are discordant. In many cases, serum testosterone... (Review)
Review
Disorders of sex development (DSD) are conditions where genetic, gonadal, and/or internal/external genital sexes are discordant. In many cases, serum testosterone determination is insufficient for the differential diagnosis. Anti-Müllerian hormone (AMH), a glycoprotein hormone produced in large amounts by immature testicular Sertoli cells, may be an extremely helpful parameter. In undervirilized 46,XY DSD, AMH is low in gonadal dysgenesis while it is normal or high in androgen insensitivity and androgen synthesis defects. Virilization of a 46,XX newborn indicates androgen action during fetal development, either from testicular tissue or from the adrenals or placenta. Recognizing congenital adrenal hyperplasia is usually quite easy, but other conditions may be more difficult to identify. In 46,XX newborns, serum AMH measurement can easily detect the existence of testicular tissue, leading to the diagnosis of ovotesticular DSD. In sex chromosomal DSD, where the gonads are more or less dysgenetic, AMH levels are indicative of the amount of functioning testicular tissue. Finally, in boys with a persistent Müllerian duct syndrome, undetectable or very low serum AMH suggests a mutation of the AMH gene, whereas normal AMH levels orient toward a mutation of the AMH receptor.
Topics: Anti-Mullerian Hormone; Disorders of Sex Development; Female; Humans; Male
PubMed: 33013698
DOI: 10.3389/fendo.2020.00619