True Hermaphroditism Research Articles

Seminoma in a Transverse Testicular Ectopia: A Rare Case Report

Transverse testicular ectopia (TTE) is an extremely rare congenital anomaly of the testis, characterized by migration of one testis toward the contrary hemiscrotum. TTE is usually associated with other testicular abnormalities such as persistent Mullerian duct syndrome, hypospadias, true hermaphroditism, and scrotal anomalies. Testicular sonography is the main initial diagnostic modality, followed by magnetic resonance imaging of the scrotum. These imaging modalities are important for determination of TTE and characterization of the testicular lesions. This case report provides the high-resolution ultrasonography, Doppler ultrasonography, magnetic resonance imaging, and diffusion-weighted imaging findings of a young man with seminoma in the transverse testicular ectopia. In addition, data on tumor stiffness, obtained with point shear-wave sonoelastography, are presented.

MON-056 Rare X Chromosome Pericentric Inversion Associated with Ovotesticular Disorder of Sex Development

Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by coexistence of ovarian and testicular parenchyma, in separate gonads or in the same gonad (ovotestis), in individuals with variable degrees of genital ambiguity. Karyotype may be 46,XX (60%), 46,XY (10%), or there may be sex chromosomes abnormalities, including mosaicism, chimerism and structural anomalies (30%). A genetic origin may be identified in some subjects with normal XX or XY karyotype, but most cases are of unknown origin. Apparently balanced chromosome rearrangements (translocations, insertions and inversions) may cause truncation, deletion, inactivation or over-expression of specific genes. We report on a case of OT-DSD associated with an X chromosome inversion. Case report: A 3-month old girl was referred due to atypical genitalia. She was born at term to a 42 years old G3P2A1 mother and her 45 years old unrelated husband with normal weight, length and head circumference. She had normal development, no associated health problems, and family history was unremarkable. Physical examination revealed a 3.1-cm phallus with chordee, scrotal hypospadias, partial penoscrotal inversion and a 0.5 cm3 right gonad palpable in the inguinal region; there were no associated dysmorphic features. At 1.5 months there were normal levels of FSH (3.09 IU/L) and LH (3.67 IU/L), and testosterone (155 ng/dL) was in the normal male range. Ultrasound revealed normal uterus and gonads were in the inguinal regions. Urethra-cystoscopy and vaginoscopy at 9 months revealed a urogenital sinus with high vaginal confluence. Laparoscopy and gonadal biopsies were also performed; the left gonad was an ovotestis with multiple ovarian follicles, while the right gonad was a testis. In both gonads the seminiferous tubules had only Sertoli cells. Karyotype revealed a pericentric X chromosome inversion, 46,X,inv(X)(p22.1q26)dn[20]. FISH on peripheral blood and cultured cells from the right gonad with probes for X (DXZ1) and Y (DYZ3) centromeres and SRY (Yp11.3 - 122 Kb) showed only two X chromosome signals. Array GH analysis (Cytoscan 750K, Affymetrix) showed a 1.3 Mb deletion distal to the short arm breakpoint (Xp22.31), which was reported as VOUS, and a 9 Mb region of LOH on chromosome 9. Discussion: Several cases of X pericentric inversion with different breakpoints have been reported; though phenotypes of female heterozygotes are often normal, early menopause, irregular menses, gonadal dysgenesis or sterility have been described. In this case, it is plausible that the genomic rearrangement could have affected long-range regulation of SOX3 (located in Xq27.1) resulting in ectopic expression of this gene in the bipotential gonad. In addition, the features detected in array GH may have a role in the phenotype. Different methods to determine the exact chromosomal breakpoints and copy number variations in this region will be required.

Gonadal Dominance and Internal Genitalia Phenotypes of Patients with Ovotesticular Disorders of Sex Development: Report of 22 Cases and Literature Review

This study aimed to delineate internal genitalia phenotypes in patients with ovotesticular disorders of sex development (OT-DSD). Therefore, a cohort of 22 OT-DSD patients admitted to the Peking Union Medical College Hospital from March 1977 to August 2019 was analyzed retrospectively. The characteristics of karyotype, gonad type and location, and internal genital organs were reviewed and compared to 242 pooled cases from the Chinese literature. As a result, the most common karyotype was 46,XX (68.2% in 22 cases of our hospital, 60.8% in the domestic literature). The combination of gonads was separated (ovary-testis, 45.1%), unilateral (ovotestis-ovary, 17.4%; ovotestis-testis, 13.0%), and bilateral (ovotestis-ovotestis, 24.5%). All the cases in our hospital had a uterus on the side of the ovary or ovotestis. Among the 19 female patients, 5 had a hysterectomy due to genital tract obstruction, 9 had vaginal dysplasia, 3 had premature ovarian failure, and only 2 women gave birth to a child. In conclusion, OT-DSD is a typical model of unilateral gonadal determinism: the uterus is present on the side of the ovotestis and ovary and the internal genital organs predominantly exhibit female characteristics. However, combined reproductive tract malformation and ovarian function of premature failure are not uncommon.

Prostatic Metaplasia of the Vagina and Uterine Cervix: An Androgen-associated Glandular Lesion of Surface Squamous Epithelium.

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.

53. Ovotesticular Disorder of Sex Development in Korean Children : Differentiating Ovotesticular Disorder of Sex Development from Others

53. Ovotesticular Disorder of Sex Development in Korean Children : Differentiating Ovotesticular Disorder of Sex Development from Others

Disorders of Sexual Development: Presentation and Categorization at Allied Hospital / Punjab Medical College Faisalabad, Pakistan

Background: Ambiguous genitalia is a condition in which external genitalia of the patients are ambiguous (not clearly male or female) or their external genitalia do not match with the chromosomal sex. It’s a rare condition and its incidence is 1.7%, or others say 1/5500 live births. Current nomenclature defines it as “disorder of sexual development” (DSD). It is generally divided into six categories; 46 XY DSD,46 XX DSD, chromosomal DSD, ovo-testicular DSD, 46 XY complete gonadal dysgenesis & 46XX testicular DSD. I_DSD registry (Glasgow) is the largest organization which registers such cases for clinical research and standardizes the information. Data from 51 centers from 36 countries across the globe is being uploaded there. Urology Department of Allied Hospital Faisalabad is the only center from Pakistan which registers its cases. Objectives: To identify and categorize different presentations of DSD according to the standard nomenclature. 2-To register the cases of DSD to I-DSD registry in Glasgow to be included in further clinical research. Study Design: Retrospective study. Settings: Urology Department Allied Hospital Faisalabad, Pakistan. Duration: From 01-09-2008 to 31-08-2019. Inclusion Criteria: All the patients with indeterminate sex / ambiguous genitalia presenting to OPD of Allied hospital Faisalabad irrespective of age Exclusion Criteria: Patients previously operated for DSD / with unrecorded data at first presentation. Methodology: Relevant data was retrieved from patients’ charts taken from hospital records, with the permission of hospital administration to publish their data. Patients had been evaluated with history/examination for phenotypical sex, with karyotyping for chromosomal sex, and ultrasonography & hormonal analysis (serum testosterone, FSH, LH and Estradiol) for gonadal sex. Specific tests like 17-OH levels performed in selected patients (CAH). Gender assignment was done according to chromosomal sex, after counselling of parents and adult patients. Results: Total 34 patients were enrolled. Mean age at presentation was 16.38 ± 9.38 years (range 10 months to 42 years). Nine of 34 patients were brought up as females, one as intersex and 24 as males. After categorization of various clinical presentations according to standard nomenclature, 27(79.4%) belonged to 46XY DSD category, 03(8.80%) to 46XX DSD, 02 (5.88%) to chromosomal DSD, 01(2.90%) was 46XY complete gonadal dysgenesis and 01(2.90%) patient belonged to ovo-testicular DSD. None of the patients had 46XX testicular DSD. Among the presumed female patients, six were chromosomally male and were having perineal hypospadias and were later assigned the male gender. Among the presumed male patients, two were diagnosed as CAH patients with XX genetic makeup. Three patients were having exstrophy epispadias complex, 15 patients were having perineal hypospadias (majority with undescended testes) and 7 had penoscrotal hypospadias. Conclusion: Identification & categorization of indeterminate sex and gender assignment is mandatory for social & psychological well-being of patients and their families.

Case of True Hermaphroditism with XY Karyotype in a Holstein Heifer

間性が疑われるとの主訴で日本大学付属動物病院に来院したホルスタイン種育成牛について，雌雄判別を目的とした検査を行った．染色体検査では，95細胞のすべてがXY型であった．ヒト絨毛性性腺刺激ホルモン（hCG）負荷試験における血漿中テストステロン（T）濃度は低値を示した．抗ミューラー管ホルモン（AMH）濃度は0.02ng/ml であった．Sex-determining region Y（Sry）遺伝子検査は陽性で，病理解剖検査では卵巣，子宮，子宮頸管及び腟が認められ，腟とこれに連続する外陰部が肛門より36cm下方に位置し，膀胱から連続した尿道は皮下を走行し外陰部に開口していた．左側卵巣様構造物には，小型の卵胞様構造物及び精細管様構造が散在し，同右側は左側と同様の所見に加えて複数の大型囊胞状構造物が認められた．以上より，本症例はXY/femaleの真性半陰陽と確定診断した．本症例のように，T及びAMH濃度が低くhCG負荷試験に反応しない場合には，機能的な精巣の存在は否定でき，無処置で肥育しても肉質が悪化する，雄性が発現し飼養管理が困難となるといった影響はないと考えられる．

46 XY disorder of sex development: case report

Ovotesticular disorder of sex development (DSD) is an uncommon disorder. The patients have gonads of both sexes. The purpose of this study is to give information about incidence of ovotesticular disorder of sex development along with its management at Saiful Anwar General Hospital, Malang, Indonesia. We present a case of 46,XY ovotesticular DSD in a 12 year-old child. A 12 year old child had complained of disorder of genitals organ since birth. The patient had a penis, one testis and a vagina-like structure. Patient had karyotype 46 XY. His ultrasound showed testis in the left inguinal canal, right testicle undetected, uterus like organ with hematometra, ovary undetected, and testicle like organ was seen in the left lower abdomen. MRI examination showed undescended testis and there was no uterus and ovaries. Laparoscopy was done to bring the undescended testis down, but the action failed because the tissue was too short. Histological and biopsy of both gonads showed right ovary with fimbriae, and left testicle. He then underwent laparoscopic Fowler Stephen due to short testicular tissue. In this case psychiatric consultation and family support is also needed to make a decision about what to do next. This is a rare and difficult case, the diagnosis and treatment of this disorder needs multidisciplinary experts.

"Spectrum of 46 XY Disorders of Sex Development": A Hospital-based Cross-sectional Study.

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.

Pubertal outcomes and sex of rearing of patients with ovotesticular disorder of sex development and mixed gonadal dysgenesis.

PurposePatients with ovotesticular disorder of sex development (DSD) and mixed gonadal dysgenesis (MGD) usually present with asymmetric gonads and have wide phenotypic variations in internal and external genitalia. The differential diagnosis of these conditions is based on karyotype and pathological findings of the gonads. This study investigated the clinical features at presentation, karyotype, sex of rearing, and pubertal outcomes of patients with ovotesticular DSD and MGD.MethodsThe study comprised 23 patients with DSD who presented with asymmetric gonads. The presenting features, karyotype, sex of rearing, and pubertal outcomes were reviewed retrospectively.ResultsAll 23 patients presented with ambiguous genitalia at a median age of 1 month (range, 1 day–1.6 years). Müllerian duct remnants were identified in 15 of 23 patients (65.2%). Fourteen patients were diagnosed with ovotesticular DSD, whereas the other 9 were diagnosed with MGD. Eight of 14 patients (57.1%) with ovotesticular DSD were raised as males, while 7 of 9 patients with MGD (77.8%) were assigned as males. One male-assigned patient with ovotesticular DSD changed to female sex at age 20 years.ConclusionsPatients with ovotesticular DSD and MGD manifest overlapping clinical presentations and hormonal profiles. It is difficult to determine the sex of rearing and predict long-term pubertal outcomes. Therefore, long-term follow-up is required to monitor spontaneous puberty, sex outcome, and urological and gynecological complications.

Etiology and Clinical Presentation of Disorders of Sex Development in Kenyan Children and Adolescents.

Objective The purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). Methods This retrospective study included patients diagnosed with DSD who presented at ages 0–19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude's Children's (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. Results Data from the records of 71 children and adolescents were reviewed at KNH (n = 57, 80.3%) and GCH (n = 14, 19.7%). The mean age at the time of diagnosis was 2.7 years with a median of 3 months. Thirty-nine (54.9%) children had karyotype testing done. The median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3–8.9) and 8.3 years (3.6–12.1), respectively (p=0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. There were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. The most common presenting symptom was ambiguous genitalia, which was present in 66 (93.0%) patients either in isolation or in association with other symptoms. An ambiguous genitalia was initially observed by the patient's mother in 51.6% of 62 cases despite the high rate (84.7%) of delivery in hospital. Seventeen (23.9%) of the cases had a gender reassignment at final diagnosis. A psychologist/psychiatrist or counselor was involved in the management of 23.9% of the patients. Conclusion The commonest presumed cause of DSD was ovotesticular DSD in contrast to western studies, which found CAH to be more common. Investigation of DSD cases is expensive and needs to be supported. We would have liked to do molecular genetic analysis outside the country but financial challenges made it impossible. A network for detailed diagnostics in resource-limited countries would be highly desirable. There is a need to train health care workers and medical students for early diagnosis. Psychological evaluation should be carried out for all patients at diagnosis and support given for families.

Late-onset vanishing testis-like syndrome in a 38,XX/38,XY agonadic pig (Sus scrofa).

Here we describe the case of a pig with intersex traits including ambiguous external genitalia, sex chromosome abnormalities and a late-onset vanishing testis-like syndrome. It was identified shortly after birth by presenting a predominantly female phenotype with two large scrotal masses resembling testes. The karyotype is 38,XX (53%)/38,XY (47%). Sex steroid levels were undetectable at 1 and 7 months old, whereas circulating cortisol levels were typical. DNA studies excluded gene alterations in sex-determining region Y (SRY), dosage-sensitive sex reversal-congenital adrenal hypoplasia critical region on the X chromosome protein 1 (DAX1), SRY-related high mobility group-box gene 9 (SOX9), nuclear receptor subfamily 5, group a, member 1 (NR5A1), nuclear receptor subfamily 3, group c, member 4 (NR3C4) and steroid 5-alpha-reductase 2 (SRD5A2). At 8 months of age the XX/XY pig evinced delayed growth; however, the most striking phenotypic change was that the testes-like structures completely vanished in a 2-3-week period. The internal genitalia were found to consist of a portion of a vagina and urethra. No fallopian tubes, uterus or remnants of Wolffian derivatives were observed. More importantly, no testes, ovaries, ovotestis or gonadal streaks could be identified. The XX/XY sex chromosome dosage and/or overexpression of the DAX1 gene on the X chromosome in the presence of a wild-type SRY gene may have caused this predominantly female phenotype. This specimen represents an atypical case of 38,XX/38,XY chimeric, ovotesticular disorder of sex development associated with agonadism.

Outcome of feminizing genital reconstruction in female sex assigned disorder of sex development in a low-income country

Summary Background In patients with disorders of sex development (DSD), surgical/medical treatments are undertaken after sex assignment to ensure congruent bodily appearance and function. Genital reconstruction in these patients can be daunting with varied outcome. Understanding these outcomes is imperative, more especially in a developing country where added challenges exist. Objective This study evaluates the outcome of genital surgery in patients with DSD assigned female sex. Methods A retrospective analysis of 25 cases of female sex assigned DSD managed in two tertiary centers in southeast Nigeria was performed. Data of these cases were collected from the case notes, discharge summaries, and theater records. IBM SPSS Statistics Data Editor, version 21, was used for data entry and analysis. Results The patients presented at median age of 12 months (range 2 days–30 years), with 15 (60%) cases reared as female and 10 (40%) reared as male before presentation. The predominant phenotype was phallus with empty fused/unfused labioscrotum and urethra opening in the labioscrotum or perineum in 21 (84%) patients. Evaluation revealed features suggestive of 46XX DSD in 21 (84%) patients, ovotesticular DSD in two (8%), and androgen insensitivity in two (8%). A total of 10 cases required sex reassignment after evaluation. Overall, 24 of the 25 cases had feminizing genital procedures. After a median follow-up period of 2 years (range 2 months–8 years), six (25%) cases developed procedure-related complications, three (12.5%) had social maladjustment, and two (8.3%) patients reported features of gender dysphoria. Discussion The procedures of feminizing genitoplasty in this study did not differ from the established procedure. However, as a result of challenges of delayed presentation, inadequate early management, sociocultural factors, and a lack of facilities for full evaluation, some cases may require sex reassignment and more daunting reconstructive procedures. This may give rise to less than optimal outcome. The study was limited by the retrospective nature, small number of cases, and the short duration of follow-up of the cases. Conclusion Feminizing genital procedures for DSD in our setting may be associated with procedure-related complications and non-surgical complications. Improving surgical technique and addressing the challenges of delayed presentation and fixation on male gender may improve overall outcome. The operative procedures and the outcome are summarized in the following table. Feminizing genital procedures and the outcome in the female sex assigned DSD patients Procedure n (%) Surgical complications Psychosocial sequelae Nil Surgical wound infection Vaginal stenosis *Social maladjustment Gender dysphoria Clitoroplasty and vulvoplasty 12 (48%) 12 0 0 0 0 Clitoroplasty, vulvoplasty, and prepubertal cutback vaginoplasty 5 (20%) 1 0 4 1 1 Clitoroplasty, vulvoplasty, and postpubertal cutback vaginoplasty 3 (12%) 0 0 0 2 1 Orchidectomy, clitoroplasty, labioscrotal reduction vulvoplasty, and colon substitution vaginoplasty 2 (8%) 1 1 0 0 0 Orchidectomy, clitoroplasty, labioscrotal reduction vulvoplasty, and awaiting colon substitution vaginoplasty 2 (8%) 1 1 0 0 0 No procedure (parents refused assigned gender) 1 (4%) – – – – – Total 25 15 2 4 3 2 ∗CAIS, complete androgen insensitivity syndrome

Special edition of the SAMJ devoted to cell and gene therapy.

Ancient Hebrew literature as well as the New Testament differentiate between castrated eunuchs and congenital eunuchs. Congenital eunuchism is very rare today, and assuming that this was also the case in classical times, we investigated possible reasons why congenital eunuchs feature prominently. We discuss the probability that the concept 'congenital eunuchism' might in ancient times have included effeminate men who, according to cultural views on 'maleness' and androgyny, were almost equated with eunuchs. The causes of congenital hypogonadism are reviewed in order to attempt clarification of the condition of Favorinus, a congenital eunuch in the second century AD. We suggest that although he might have been a true hermaphrodite, as suggested by some authors, it is more likely that he had one of the following conditions: functional prepubertal castrate syndrome, testicular gonadotrophin insensitivity, selective gonadotrophin deficiency or Reifenstein's syndrome.

Influence of some etiological factors on development of gynecological patholo-gy and infertility of cats

The article provides an overview of professional literature on reproductive studies of cats, the definition of the main factors influencing the development of infertility in cats: hormonal changes, lack of sufficient stimulus during pairing, leading to ovulation, inability to fuse, ovarian cyst, chronic inflammatory processes in reproductive organs systems, infections, some parasites or the simplest, hereditary problems, including chromosomal abnormalities (genetic or congenital defects such as pseudoharmophioditis, true hermaphroditism, mosaicism, infantilism, freemantry) described congenital aplasia of the ovaries, trauma affecting the reproductive organs. The conditions of detention that considerably affect the reproductive system are considered. It has been established that insufficient stimulation is one of the most common causes of infertility, which is relevant for cats because they are characterized by induced ovulation. Most animals with an abnormal set of sex chromosomes are infertile, treatment methods have not been developed. Inadequate feeding is perhaps the most important cause of infertility in cats. The connection between lack and (or) excess in the diet of Calcium, Phosphorus, Iodine, Cobalt, Cuprum, Manganese, other macro-and micro elements, and inability to reproduce is established. The role of microorganisms in the emergence of infertility of cats of infectious diseases (leukemia, infectious peritonitis, panleukopenia, chlamydia, toxoplasmosis) is considered. Extension of the intraperitoneal period arises from the stage of the anestrus. Such clinical picture is observed in cats older than 8 years with hypothyroidism and hyperadrenocorticism, obesity and cachexia, the appointment of drugs with antinuclear activity. Among gynecological diseases in cats, the most common diseases are pyometra, endometritis and vaginitis. It has been established that the most frequently diagnosed diseases of the uterus of female dogs and cats are cystular hyperplasia of the endometrium in combination with the pythometer, data on the etiopathogenesis of these diseases is given. The scientific data on the application of ultrasound diagnostics, hormonal level studies, vaginal cytology, the use of hysterosalpingography, x-ray for more accurate diagnostics of causes of infertility of cats are given.

Association between polymorphisms in the SOX9 region and canine disorder of sex development (78,XX; SRY-negative) revisited in a multibreed case-control study.

Testicular or ovotesticular disorders of sex development (DSD) in individuals with female karyotype (XX) lacking the SRY gene has been observed in several mammalian species, including dogs. A genetic background for this abnormality has been extensively sought, and the region harboring the SOX9 gene has often been considered key in canine DSD. Three types of polymorphism have been studied in this region to date: a) copy number variation (CNV) in a region about 400 kb upstream of SOX9, named CNVR1; b) duplication of SOX9; and c) insertion of a single G-nucleotide (rs852549625) approximately 2.2 Mb upstream of SOX9. The aim of this study was thus to comprehensively analyze these polymorphisms in a large multibreed case-control cohort containing 45 XX DSD dogs, representing 23 breeds. The control set contained 57 fertile females. Droplet digital PCR (ddPCR) was used to study CNVR1 and the duplication of SOX9. Fluorescent in situ hybridization (FISH) was used to visualize copy numbers on a cellular level. The Sanger sequencing approach was performed to analyze the region harboring the G-insertion. We confirmed that CNVR1 is highly polymorphic and that copy numbers varied between 0 and 7 in the case and control cohorts. Interestingly, the number of copies was significantly higher (P = 0.038) in XX DSD dogs (mean = 2.7) than in the control females (mean = 2.0) but not in all studied breeds. Duplication of the SOX9 gene was noted only in a single XX DSD dog (an American Bully), which had three copies of SOX9. Distribution of the G-nucleotide insertion was similar in the XX DSD (frequency 0.20) and control (frequency 0.14) cohorts. Concluding, our study showed that CNVR1, located upstream of SOX9, is associated with the XX DSD phenotype, though in a breed-specific manner. Duplication of the SOX9 gene is a rare cause of this disorder in dogs. Moreover, we did not observe any association of G-insertion with the DSD phenotype. We assume that the genetic background of XX DSD can be different in certain breeds.

True Hermaphroditism in a Dog: A Case Report

Bu calismada, gercek hermafrodit bir kopek anlatilmistir. Vulvasindan disariya dogru cikan buyuk bir kitle olan 8 aylik melez bir kopek kisirlastirma operasyonu icin arastirma merkezimize getirildi. Fiziksel muayenelerde os klitorisin varligi ve bunun bazalinde uretral deligin oldugu saptandi. Teshis ve tedavi amaciyla hayvana ovariohysterectomie operasyonu uygulandi. Her iki gonadal doku ve uterus patolojik incelemeler icin laboratuvara gonderildi. Mikroskobik incelemeler, sag gonadin hem testis gibi seminifer tubuller hem de ovaryum gibi primer folikuller icerdigini gosterdi. Serum progesteron, 17β-ostradiol ve testosteron duzeyleri sirasiyla 0,188 ng/ml, 23,61 pg/ml, 1,008 ng/ml olarak olculdu. Kopekte her iki gonadal dokunun ayni anda bulunmasi nedeniyle olgunun bir gercek hermafrodismus olgusu oldugu kanisina varildi.

Molecular epidemiology of human papillomaviruses from cervical samples in Ethiopia: A systematic review

Disorders of sex development (DSDs) are congenital malformations defined as discrepancies between sex chromosomes and phenotypical sex. Testicular or ovotesticular XX DSDs are frequently observed in female dogs, while monogenic XY DSDs are less frequent. Here, we applied whole genome sequencing (WGS) to search for causative mutations in XX DSD females in French Bulldogs (FB) and American Staffordshire Terries (AST) and in XY DSD Yorkshire Terries (YT). The WGS results were validated by Sanger sequencing and ddPCR. It was shown that a missense SNP of the PADI6 gene, is significantly associated with the XX DSD (SRY-negative) phenotype in AST (P = 0.0051) and FB (P = 0.0306). On the contrary, we did not find any associated variant with XY DSD in YTs. Our study suggests that the genetic background of the XX DSD may be more complex and breed-specific.

COMBINATIVE VARIABILITY IN THE TREMATODAS

Objective: To study the combinational variability in trematodes based on micromorphological studies of their gametogenesis and fertilization.Trematodes: Fasciola hepatica, Opisthorchis felineus, Clonorchis sinensis, Paragonimus westermani were obtained by dissecting animals. Trematode marites were fixed in 10% neutral formalin. The treatment was carried out according to the histological method. The material was embedded in paraffin. Sections of 5–6 microns thick were stained using histological methods of staining: hematoxylin Carazzi-eosin, gallocyanin, azur-eosin according to Romanovsky-Giemsa. 400 histological specimens were manufactured; studied under a light microscope and took photomicrographs.Trematodes are characterized by true hermaphroditism. In each individual of the trematode, the sex glands are well developed – the testes and ovaries, in which the processes of gametogenesis take place: spermatogenesis and ovogenesis. As a result of gametogenesis, due to meiotic crossing-over, genetic material recombines, and trematode sex cells are formed with a unique genome. Two trematodes participate in fertilization, which, mating, fertilize each other in a cross way (simultaneous fertilization). As a result, the genetic material of each trematode is updated and a new generation of individuals with a new genotype ripens in each of them. The constant updating of the trematode genomes forms the basis of combinational variability and ensures the prosperity of species.

Ovotesticular Disorder of Sex Development: A Rare Case of Lateral Subtype 45X/46XY kariotype Diagnosed in Adulthood

A 53-year-old male referred to our centre because of hypergonadotropic hypogonadism detected during urological follow-up for urethral lithiasis. Physical examination showed short stature, micropenis, ambiguous external genitalia, and normal secondary sexual characteristics. Karyotype: 45 × 0/46XY. Abdominal MRI revealed the presence of uterus-like structure, right annex, and left testes without prostate. He underwent laparoscopic removal of dysgenetic tissues; histologic examination confirmed the presence of little uterus, fallopian tubes, little atrophic ovary, and vaginal tract; left testes was atrophic with sclero-jalinosis of seminal tubes and Leydig's cells hyperplasia. Testosterone replacement therapy was started after surgery and prostate became MRI visible after 2 years.