Disorders Of Sexual Differentiation Research Articles

Posterior Sagittal Approach for Nonanorectal Malformation: Widening Spectrum.

Posterior sagittal is a very well accepted approach in the treatment of anorectal malformations. This approach provides good access and exposure through the perineum to the deep pelvic structures. It reduces risk of injury to important structures as dissection remains in midline. To access feasibility of posterior sagittal approach for non-anorectal malformation indications and to widen the spectrum. We present a series of 10 cases of non-anorectal malformations operated by this approach for 4 years. Six patients included in the study were of Disorders of Sexual Differentiation with pseudovagina, three of Y duplication of the urethra, and one of cervical atresia. All patients had good results. Posterior sagittal approach is feasible, safe with minimal bleeding, and no postoperative incontinence. It can safely be used for non-anorectal indications.

An approach to the management and care of an individual with 46, XX ovotesticular disorder of sexual differentiation

Ovotesticular disorder of sexual differentiation (OT-DSD) is a rare condition defined by the presence of both testicular and ovarian elements in the same individual. Definitive diagnosis is made based on histological assessment of the gonad/s confirming both ovarian and testicular components. In this paper, we describe how a diagnosis of 46XX, OT-DSD was made in a 20-year-old individual with enlarged breasts and ambiguous genitalia. The initial impression was congenital adrenal hyperplasia (CAH) based on 46, XX karyotype and absence of testes on physical examination and imaging. However, biochemical tests were inconsistent with CAH, hence a more probable diagnosis of 46, XX OT-DSD was considered. The patient suffered from gender dysphoria and after extensive counseling, he decided to undergo gender-affirming surgery: laparoscopic excision of the left gonad, subtotal hysterectomy, bilateral mastectomy, and a masculinizing genitoplasty. Histopathology of the left gonad revealed an ovotestes which confirmed the diagnosis of 46, XX OT-DSD.

Adolescent females with 46, XY Disorders of Sexual Differentiation

Disorders of sex development are congenital conditions where chromosomal, gonadal and anatomical sex of an individual is atypical. The sex of an individual is governed by chromosomal complement, which in turn decides the development of bi-pontential gonad and differentiation of external as well as internal genitalia into a definitive human sex either male or female. Though this is the general plan of sex development, most of the times in spite of being normal chromosomal complement, the gonadal and/ or genital sex is discordant leading to conditions known as disorders of sex development. Depending upon the chromosomal complement, these conditions are classified as (a) sex chromosome DSD (b) 46, XY DSD and (c) 46, XX DSD. Though most of the DSDs present at infancy with genital ambiguity and other clinical features, some of these conditions may not present or get recognized until adolescence and presenting as lack of pubertal development or primary amenorrhea. This leads to a social stigma to the patient as well as the family members and proper counselling and management of these cases can be improved by understanding the molecular pathology of these conditions. This review helps to understand the molecular genetics of 46, XY DSD in adolescent females who present as lack of puberty and primary amenorrhea.

Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3β-hydroxysteroid dehydrogenase type 2 deficiency accounts for less than five percent of all CAH cases. We report two Moroccan twins from a spontaneous triplet pregnancy. The 46,XY newborn exhibited a disorder of sexual differentiation (DSD) with hypo virilization, while the 46,XX newborn had normal female external genitalia. In the first week of life, they showed hyponatremia and primary adrenal insufficiency with a slight 17OHP elevation and increased DHEAS and renin levels. The aCGH-SNP analysis disclosed a 8.36 Mb long contiguous stretch of homozygosity (LCSH) on chromosome 1p13.2-p11.2 including the candidate HSD3B2 gene, a LCSH of 7.3 Mb on 14q31.1-q32.11, and a 7 Mb duplication on 10q22.3-q23.2. Clinical exome sequencing revealed the biallelic c.969T > G (p.Asn323Lys) HSD3B2, likely pathogenic, variant in both of the affected twins. This case emphasizes the importance of a prompt molecular diagnosis performed through the combination of aCGH and clinical exome, both for establishment of correct therapy and for follow-up, as the newborns also carry a genomic rearrangement with possible clinical implications.

RF02 | PMON309 Two Siblings with p.Arg92Trp Variant in NR5A1 Presenting with Testicular Disorder of Sexual Differentiation

Abstract Introduction Disorders of sexual differentiation (DSD) are conditions of abnormal chromosomal development leading to atypical gonadal and anatomic sexual characteristics. We present the case of two siblings with 46, XX testicular DSD due to a mutation in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1). While there is extensive literature about pathogenic variants of this gene, this is the first variant that has been shown to cause DSD in XX individuals, rather than XY. Case presentation This is the case of a sibling pair with male phenotype and history of hypospadias and hypogonadism in the setting of 46, XX karyotype. Sibling A presented with hypospadias at birth and hypergonadotropic hypogonadism in childhood, initially managed with testosterone. Testicular biopsy revealed bilateral germ cell aplasia with degeneration of seminiferous tubules. Sibling B presented at age 8 with precocious puberty. He had a history of hypospadias and cryptorchidism at birth. Gonadotropins and testosterone levels were prepubertal. Testicular biopsy showed only Sertoli cells. Their adrenal gland and thyroid function was normal, their bone age was advanced. FISH was negative for the SRY gene in both cases, no ovaries or mullerian structures found in pelvic imaging. DSD genetic panels were sent, resulting positive for the R92W variant in NR5A1. Neither of them have intellectual disability; however, sibling B has attention deficit and hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Family history is remarkable for two uncles that have been unable to conceive. Their mother had oligomenorrhea and difficulty conceiving, typical presentation of a female carrier of this mutation. Discussion and conclusions The majority of DSD in individuals with a 46, XX karyotype are due to congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency, however, mutations in NR5A1 have been among the most frequently identified genetic causes of gonadal development disorders and are associated with a wide phenotypic spectrum. NR5A1 is an essential transcription factor that regulates target genes crucial for normal reproductive physiology and endocrine function, controlling several steps of adrenal and gonadal development. While there is extensive literature about the phenotype caused by variants of NR5A1 in XY individuals, the recurrent heterozygous p.Arg92Trp NR5A1 variant R92W that our patients have, is the only one that has been shown to cause DSD in XX individuals, with variable degrees of testis development. It has previously been described, however, in women with primary ovarian insufficiency (POI). Morevariants of this gene will continue to arise, playing a pivotal role in reproductive endocrinology. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Development of the human ovary: Fetal through pubertal ovarian morphology, folliculogenesis and expression of cellular differentiation markers

A definition of normal human fetal and early postnatal ovarian development is critical to the ability to accurately diagnose the presence or absence of functional ovarian tissue in clinical specimens. Through assembling an extensive histologic and immunohistochemical developmental ontogeny of human ovarian specimens from 8 weeks of gestation through 16 years of postnatal, we present a comprehensive immunohistochemical mapping of normal protein expression patterns in the early fetal through post-pubertal human ovary and detail a specific expression-based definition of the early stages of follicular development. Normal fetal and postnatal ovarian tissue is defined by the presence of follicular structures and characteristic immunohistochemical staining patterns, including granulosa cells expressing Forkhead Box Protein L2 (FOXL2). However, the current standard array of immunohistochemical markers poorly defines ovarian stromal tissue, and additional work is needed to identify new markers to advance our ability to accurately identify ovarian stromal components in gonadal specimens from patients with disorders of sexual differentiation.

From Conception to Adulthood: The Impact of Androgens on Abnormalities of Male Genital Development and Size

Androgens play a critical role in male development starting in utero. In a 46XY male patient, testosterone plays a significant role in the development of the internal genitalia while external genitalia formation is largely dependent on the conversion of testosterone to dihydrotestosterone (DHT). Testosterone is important for testicular descent and later, the onset of puberty. Defects in the production of testosterone, the conversion of testosterone to DHT, or within the androgen receptor can lead to a variety of pediatric urological conditions including micropenis, cryptorchidism, hypospadias, and disorders of sexual differentiation. Supplementation with testosterone is the standard of care for the treatment of micropenis and is used to increase glans size and reduce complications before hypospadias repair. Unfortunately, patients with a 5-alpha reductase deficiency will respond sub-optimally to testosterone supplementation and instead may benefit from DHT supplementation.

The Combination of Chromosomal Reorganization and Inherited Point Mutation Has Led to the Development of a Rare Clinical Phenotype in a Patient with Disorder of Sex Differentiation and Neuromuscular Pathology

The Combination of Chromosomal Reorganization and Inherited Point Mutation Has Led to the Development of a Rare Clinical Phenotype in a Patient with Disorder of Sex Differentiation and Neuromuscular Pathology

Characterization of a cohort of pediatric patients with Congenital Adrenal Hyperplasia

Observational descriptive longitudinal study. Medical records from the pediatric endocrinology outpatients from four institutions in Medellín, Colombia were reviewed. Sociodemographic, clinical (type of CAH, salt-wasting crisis, associated endocrinopathies), labora tory (17-hydroxyprogesterone, testosterone, dehydroepiandrosterone sulfate, androstenedione, cor tisol, and adrenocorticotropic hormone) variables were analyzed. A descriptive statistical analysis was carried out. 132 patients (65% female) were included. The median age at diagnosis was 2 months, 44.7% neonatal diagnosis. Seventy-nine children with classical salt-wasting CAH, 31 with simple virilizing, and 22 with non-classical form were documented. Median 17-OHP at diagnosis was 4820 ng/dl. Sexual differentiation disorder was presented in 47% of patients and 48% presented with adrenal crisis (AC) at diagnosis; the median age of the first AC was 15 days. Ninety-three patients required fludrocortisone and 32 patients presented AC after diagnosis and treatment. Median height/ age (last appointment): -0.49 SD, difference between bone and chronological age: 26 months. More than 60% of patients had elevated androstenedione and/or testosterone at the last appointment. Sociodemographic and clinical characteristics are similar to those reported in the literature. In 48% of patients, AC was the initial manifestation, making neonatal screening important, as it would allow an early diagnosis. We found virilization in 71% of women in our study. A CAH should be suspected in a newborn with different genitalia.

Clinical observation of gonadal dysgenesis with surgical correction

Anomalies of sexual development, despite their low prevalence, are relevant both due to the rapid expansion of diagnostic capabilities at the genetic and genetic levels, and due to increasing attention to the social adaptation of such patients. This article is devoted to the description of clinical observation of a rare form of sexual rosette anomalies – Swyer syndrome, which consists in the underdevelopment male gonads in persons with 46XY karyotype. The most common and studied cause of male gonadal dysgenesis is a SRY gene mutation, which is responsible for testicular development. So far, several point mutations in genes involved in the development of male gonads have been identified. Genes are located in both autosomes and both sex chromosomes. One of the newest pathogenetic mechanisms of this syndrome is a MYRF gene mutation. The main consequence of this mutation is a violation of myelination, its role in disorders of sex differentiation has recently been shown. Patients with Swyer syndrome at birth have phenotypic traits of the female sex. Delayed sexual development is registered in adolescence; ultrasound reveals a hypoplasia of the uterus, gonads in the form of fibrous bands. Clinical observation of a 27-year-old patient with complaints of lack of menstruation, coarsening of the voice and facial hair growth is present. Examination revealed the female type structure of the external genitalia, clitoral hypertrophy, vaginal aplasia, 46XY genotype, MYRF mutation. Surgery was performed. It included cystoscopy (free urethra, ureteral stenting), laparoscopy (uterus and ovaries in the pelvic cavity are not visualized, gonads are found at the level of the inguinal ring and removed), transperitoneal tunneling of the vagina, dissection of the vertical membrane of the vagina, removal of the clitoris, resection of the labia minora. Patient underwent complete physiological and social adaptation 6 months after operation.

Demayo Sandra

Introduction: Usual sex determination and differentiation occurs progressively during the period of embryonic development, involving chromosomal differentiation, gonadal differentiation, and somatic or genital differentiation. Swyer syndrome is a disorder of sex chromosomes and sexual differentiation characterized by 46, XY pure gonadal dysgenesis in a phenotypically female person with primary amenorrhea, and a complete absence of functioning gonadal tissue. Gonadal malignancy occurs in 10-30% of cases, so gonadectomy is indicated at the time of diagnosis. The treatment includes, in addition to the gonadectomy, hormone replacement therapy, and psychological support. Objective: To present a case diagnosed and managed in our institution, in addition to reviewing the recent literature about this rare condition, but with a strong physical, psychological and social impact. Methods: Analysis of clinical history of a patient with Swyer's Syndrome, diagnostic and therapeutic management. Bibliographic review. Presentation of the clinical case: An 18-year-old patient attends our hospital presenting primary amenorrhea. She presents BMI: 22; Tanner stage PH III BD III, gynecological examination with vulva and vagina with normal characteristics. Hormone profile requested: FSH 96.8 mU/ml, LH 32.9 mU/ml, Estradiol <25 pg/ml; Total testosterone 0.15 ng/ml. TV ultrasound shows a hypoplastic uterus of 23x11x29 mm, ovaries are not visualized, and a heterogeneous solid image of 22x23x24 mm in the left adnexal region. 46XY karyotype. In the presence of these results, a diagnosis of Swyer's syndrome is made, so an MRI was requested, which shows a uterus of 14x20x26 mm, ovaries are not visualized, a solid lobulated oval image of 23x33x47 mm poorly vascularized standing out in the left adnexal region and free inguinal canals. It was decided to perform exploratory laparoscopy and gonadectomy. The intraoperative findings were: intrapelvic hypoplastic uterus, uterine tubes without any particularities, enlarged left gonad of approximately 3x4 cm pearly white with a hard elastic consistency, and a fibrous band in the right adnexa. Bilateral adnexectomy was performed, obtaining as a histological result well-differentiated left dysgerminoma SALL4 +, OCT3/4 +, negative Inhibin and CD 117 +, and right streak gonad. Conclusions: In the presence of a person with primary amenorrhea and absence or poor development of secondary sex characteristics, Swyer's syndrome should be suspected, and pertinent studies should be requested to arrive at the diagnosis. It is essential to perform gonadectomy at the time of diagnosis due to the risk of malignant transformation. The importance of a multidisciplinary approach and psychological accompaniment of patients and relatives is highlighted.

Diseases of the endocrine system in children in Ukraine and specialized care to pediatric patients in 2021

The article provides information on the specialized medical care to children of various ages with endocrine pathology in Ukraine in the year 2021 and presents analysis of its dynamics over the past 8—10 years, based on the data of the official statistics of the Ministry of Health of Ukraine and Ukrainian databases of children with the rare (orphan) endocrine diseases. Information is provided on the provision of pediatric endocrinologists in various regions of Ukraine, the state of inpatient care by region, the indicators of neonatal screening for congenital hypothyroidism and congenital adrenal hyperplasia, and the incidence of endocrine pathology in children under 1 year of age.The article contains data on the dynamics of the prevalence of diabetes mellitus (DM) in children, its various types, malignant diseases of the endocrine glands, in particular thyroid cancer, a database of children with disorders of sexual differentiation (DSD), etc.It is noted that according to the register of children with DM in 2021, 11 193 patients under the age of 18 (15.0 per 10,000 child population) were registered, including 11 014 (14,74) children receiving insulin therapy (with DM type 1, other types of DM with the need for insulin treatment), 51 with DM type 2, 69 children with neonatal DM, of which the diagnosis was genetically confirmed in 40, and MODY was genetically confirmed in 59 children. The prevalence of DM among children aged 0—18 in 2021 increased by 46.2 % compared to 2012. The fastest growing prevalence and incidence of diabetes was among children under 6 years of age.Children with DSD undergo a detailed cytogenetic examination in the world’s leading genetic laboratories by specialists of the Department of Pediatric Endocrinology of the Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine. The database included 682 DSD patients, in particular with chromosomal DSD — 357 (52.3%, in particular 303 patients with Turner syndrome); 46, XY DSD — 119 patients (17.5%); 46,XX — 206 patients (30.2%) (of which 185 patients with DSD due to congenital adrenal hyperplasia).

A novel variant luteinizing hormone receptor in the first transmembrane helix of two homozygous Iranian patients: case report

BackgroundLeydig cell hypoplasia (LCH) is a rare autosomal recessive endocrine syndrome that affects the normal development of male external genitalia in 46, XY individuals and is one of the causes of disorder of sexual differentiation (DSD) in males. The responsible gene of LCH is LHCGR which is located on the chromosome 2 and its various mutations lead to different degrees of the disease ranging from micropenis to complete XY DSD.Case presentationIn this study, we have investigated the clinical presentation and molecular findings of two siblings with complete male LCH and XY DSD. This is the first detailed report of individuals with LCH from Iran. It aimed to study the molecular and clinical characteristics of two sisters with type 1 LCH. Whole exome sequencing was used for these patients to find the underlying genetic cause of the disease. Our Iranian DSD patients had external genitalia (normal labia major and minor, the external opening of the urethra beneath the clitoris) and bilateral testicular tissues in the inguinal region, which were removed by surgical exploration.ConclusionsGenetic sequencing showed the homozygous variants of the LHCGR gene in the patients, a novel duplication variant in exon 11, c.1091dupT -or pLeu365Profs*5. This mutation is described as likely pathogenic. We think that this case report can widen the genotypic spectrum of the LHCGR variants. Moreover, this study emphasizes the significant rule of Whole Exome Sequencing in differentiating various causes of disorder of sexual differentiation.

Paediatric endocrine disorders at a tertiary hospital in Lagos, Nigeria

Background: The global increase in paediatric endocrine disorders (PED) is thought to be a result of multiple factors including changing lifestyles, environmental pollution and increasing awareness and diagnostic capabilities. Studies on the prevalence of paediatric endocrine disorders in the developing world are few. A preliminary audit of PED at the Lagos State University Teaching Hospital two years ago revealed type 1 diabetes mellitus as the commonest diagnosis. Since then many more children with PED continue to be referred from various centres.Objective: The aim of the present study was to describe the burden and pattern paediatric endocrine disorders over a three-year period.Subjects and Methods: Records of patients who presented in the paediatric endocrine unit between March 2017 and March 2020 were reviewed and relevant data on age at presentation, sex and diagnosis were extracted.Results: A total of 172 patients representing 0.45% of the total paediatric patients seen within the period. There were more females 90(52.3%) than males 79(45.9%) and three patients (1.7%) presented with disorders of sexual differentiation. Age of presentation ranged between 11 days and 16 years with mean of 6.27 ± 4.5 years. The commonest groups of endocrine disorders were disorders of pancreas/lipids-diabetes (n=33, 19.2%), pubertal disorders (n=25, 14.5%) and thyroid disorders (n=24, 14.0%).Conclusion: Our unit witnessed a comparatively larger case-load of PEDs compared to earlier reports from other parts of Nigeria. Diabetes mellitus, pubertal and thyroid disorders constituted the commonest paediatric endocrine disorders encountered.

Complete Androgen Insensitivity Syndrome: Primary Amenorrhoea of Rare Variety

Androgen insensitivity syndrome is an X linked disorder of male sexual differentiation caused by mutation affecting the androgen receptor gene Xq 11-12 resulting in decreased peripheral responsiveness to circulating androgens, with variable phenotypic expression.

Yolk Sac Tumor in an Infant with Androgen Insensitivity Syndrome: A Case Report and Review of the Literature

Background: Androgen insensitivity syndrome (AIS) is a disorder of sexual differentiation caused by complete or partial resistance to the biological action of androgens. The common malignant tumors associated with this syndrome are seminomas. However, the risk of malignancy in childhood remains low. Case Report: A 8-month-old child with a female phenotype and a 46, XY karyotype, presented with bilateral inguinal hernia. The patient underwent right radical inguinal orchiectomy with high ligation of the spermatic cord and laparoscopic percutaneous extra-peritoneal herniorrhaphy. Final pathology confirmed a pure yolk sac tumor (YST) from the right testis. Androgen receptor (AR) gene mutation was found in the children. The follow-up ultrasonography shown no recurrence, with serum AFP returned to normal within 3 months. Conclusion: The case we presented is relatively infrequent in the literature with yolk sac tumor in a AIS children presented with a palpable lump inguinal region.

Disorders of Sexual Differentiation: A Clinicopathological and Histological Study

Introduction: The term ‘Disorders of Sexual Differentiation’ (DSD) is defined as a congenital discrepancy between external genitalia, gonadal and chromosomal sex. The Chicago consensus based on the primary genetic defect is used for current nomenclature and classification. A child with DSD, if identified and treated early, may grow to become a well-adjusted, functional member of the society. Patients with DSD carry a low but definite risk of developing germ cell tumours which necessitates a histological analysis in all cases. Aim: To describe the clinicopathological features of individuals with DSD and to classify the available cases according to the Chicago consensus which is based on karyotype and histopathology. Materials and Methods: The study was a retrospective descriptive study done at a tertiary referral centre in South India, for a period of four months from May to August 2016. Case charts and histopathology slides of cases received in the department of Pathology from January 2011 to May 2016 were included and reviewed. Cases where the histopathology slides/blocks were not retrievable/difficult to assess due to technical issues were excluded. Case charts and slides were reviewed retrospectively with a view to classify as per karyotypic or histological classification. The slides were reviewed by two pathologists to help in the classification wherever possible. Statistical measures like mean and percentages were used to describe the results. Results: A total of 22 cases of DSD were studied for which karyotype was available in 13 cases. Common clinical presentations were primary amenorrhoea, cryptorchidism and ambiguous genitalia. Age at presentation varied from nine months to 30 years. The initial diagnosis based on karyotype, clinical findings, hormonal assays and imaging were concordant with the final diagnosis in 11 cases. In two cases, histopathology was essential in arriving at a definitive diagnosis. Of the 13 cases with karyotype reports available, five were sex chromosome DSD, five were 46XY DSD and three were 46XX DSD. Gonadoblastoma was seen in three cases. Conclusion: Histopathological examination together with karyotype plays a crucial role in proper categorisation of disorders of sexual differentiation. A multidisciplinary team approach for early diagnosis and management of DSD is essential for the psychosexual development of these individuals.

A 35-year-old father with persistent Mullerian duct syndrome and seminoma of the right undescended testis: a rare case report

BackgroundA persistent Müllerian duct syndrome is a rare disorder of sexual differentiation characterized by the presence of the female reproductive system in a normal male.Case presentationHerein, we report a case of a 35-year-old father with persistent Müllerian duct syndrome and seminoma in the right undescended testis. The exploratory laparotomy was performed and revealed a mass in the right undescended testis and Müllerian duct structures.ConclusionsFor patients with cryptorchidism and inguinal hernia, the persistent Müllerian duct syndrome should be considered, and radiological evaluation of the genitourinary system is recommended for early diagnosis of persistent Müllerian duct syndrome. The persistent Müllerian duct syndrome is usually detected during a surgical operation, and it is considered a risk factor for developing testicular malignancies.

Koro Presenting in the Prodromal Phase of Schizophrenia in a Patient With Klinefelter Syndrome

Klinefelter syndrome (KS), a disorder of abnormal sexual differentiation, is characterized by the presence of an excess X chromosome in males (47, XXY). KS is associated with various neuropsychiatric manifestations such as anxiety, depression, schizotypy, and frank psychosis. Psychosocial factors including stigma and poor coping or psychobiological comorbidities due to neuroendocrine mechanisms have been posited to explain these symptoms. We report the case of a young male with an anxious temperament who presented with the culture-bound neurosis of Koro, which evolved into schizophrenia. The patient also had gender dysphoria and significant social anxiety. The report highlights the implications of anxious traits leading to developing culture-bound neurosis in the prodromal phase of schizophrenia in a patient with KS and its influence on treatment strategies. Integrated psychopharmacological, psychological, and psychosocial interventions are required to promote recovery in patients with KS.

Analyses of Molecular Characteristics and Enzymatic Activities of Ovine HSD17B3.

Simple SummaryMutations of 17β-hydroxysteroid dehydrogenase type3 (HSD17B3) gene cause disorder of sex differentiation (DSD). In this study, the open reading frame sequence of ovine HSD17B3 was revealed, and the effects of amino acid substitution on ovine and human HSD17B3 enzymatic activities were evaluated. Although ovine HSD17B3 has a conserved amino acid sequence, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitution of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. Similarly, substitution of these amino acids of human HSD17B3 for those in ovine also did not affect the enzymatic activities. However, enzymatic activities declined in the missense mutations of the HSD17B3 gene associated with DSD, which occurred in the conserved amino acids between both species. 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) converts androstenedione (A4) into testosterone (T), which regulates sex steroid production. Because various mutations of the HSD17B3 gene cause disorder of sex differentiation (DSD) in multiple mammalian species, it is very important to reveal the molecular characteristics of this gene in various species. Here, we revealed the open reading frame of the ovine HSD17B3 gene. Enzymatic activities of ovine HSD17B3 and HSD17B1 for converting A4 to T were detected using ovine androgen receptor-mediated transactivation in reporter assays. Although HSD17B3 also converted estrone to estradiol, this activity was much weaker than those of HSD17B1. Although ovine HSD17B3 has an amino acid sequence that is conserved compared with other mammalian species, it possesses two amino acid substitutions that are consistent with the reported variants of human HSD17B3. Substitutions of these amino acids in ovine HSD17B3 for those in human did not affect the enzymatic activities. However, enzymatic activities declined upon missense mutations of the HSD17B3 gene associated with 46,XY DSD, affecting amino acids that are conserved between these two species. The present study provides basic information and tools to investigate the molecular mechanisms behind DSD not only in ovine, but also in various mammalian species.