Phenotypic variability and management of patients with mosaic monosomy X and Y chromosome material: a case series.

BACKGROUND: we aim to discuss the origin and the differences of the phenotypic features and the management care of rare form of disorder of sex development due to Mosaic monosomy X and Y chromosome materiel. METHODS: We report our experience with patients harboring mosaic monosomy X and Y chromosome material diagnosed by blood cells karyotypes and cared for in our department from 2005 to 2022. RESULTS: We have included five infants in our study. The current average age was 8 years. In four cases, the diagnosis was still after born and it was at the age of 15 years in one case. Physical examination revealed a variable degree of virilization, ranging from a normal male phallus with unilateral ectopic gonad to ambiguous with a genital tubercle and bilateral not palpable gonads in four cases and normal female external genitalia in patient 5. Karyotype found 45, X/46, XY mosaicism in patient 1 and 2 and 45, X/46, X, der (Y) mosaicism in patient 3, 4 and 5. Three cases were assigned to male gender and two cases were assigned to female. After radiologic and histologic exploration, four patients had been explored by laparoscopy to perform gonadectomy in two cases and Mullerian derivative resection in the other. Urethroplasty was done in two cases of posterior hypospadias. Gender identity was concordant with the sex of assignment at birth in only 3 cases. CONCLUSION: Because of the phenotypic heterogeneity of this sexual disorders and the variability of its management care, then the decision should rely on a multidisciplinary team approach.

"I've had constant fears that I'll get cancer": the construction and experience of medical intervention on intersex bodies to reduce cancer risk.

PURPOSE: This paper examines the subjective experience of medical interventions on intersex bodies to reduce cancer risk. METHODS: Twenty-five individuals with intersex variations took part in semi-structured interviews, analysed through thematic discourse analysis. RESULTS: Intersex bodies were positioned as inherently sick and in need of modification, with cancer risk legitimating surgical and hormonal intervention. This resulted in embodied shame, with negative impacts on fertility and sexual wellbeing. However, many participants resisted discourses of bio-pathologisation and embraced intersex status. Some medical interventions, such as HRT, were perceived to have increased the risk of cancer. Absence of informed consent, and lack of information about intersex status and the consequences of medical intervention, was positioned as a human rights violation. This was compounded by ongoing medical mismanagement, including health care professional lack of understanding of intersex variations, and the objectification or stigmatization of intersex people within healthcare. The consequence was non-disclosure of intersex status in health contexts and lack of trust in health care professionals. CONCLUSIONS: The legitimacy of poorly-evidenced cancer risk discourses to justify medical intervention on intersex bodies needs to be challenged. Healthcare practitioners need to be provided with education and training about cultural safety practices for working with intersex people.

Long-term outcomes in non-CAH 46,XX DSD.

Differences/disorders of sex development (DSD) comprise a large group of rare congenital conditions. 46,XX DSD, excluding congenital adrenal hyperplasia (CAH), represent only a small number of these diseases. Due to the rarity of non-CAH 46,XX DSD, data on this sex chromosomal aberration were confined to case reports or case series with small numbers of patients. As the literature is still relatively sparse, medical data on the long-term effects of these pathologies remain scarce. In this review, we aim to provide an overview of current data on the long-term follow-up of patients with non-CAH 46,XX DSD, by covering the following topics: quality of life, gender identity, fertility and sexuality, global health, bone and cardiometabolic effects, cancer risk, and mortality. As non-CAH 46,XX DSD is a very rare condition, we have no accurate data on adult QoL assessment for these patients. Various factors may contribute to a legitimate questioning about their gender identity, which may differ from their sex assigned at birth. A significant proportion of gender dysphoria has been reported in various series of 46,XX DSD patients. However, it is difficult to give an accurate prevalence of gender dysphoria and gender reassignment in non-CAH 46,XX DSD because of the rarity of the data. Whatever the aetiology of non-CAH 46,XX DSD, fertility seems to be impaired. On the other hand, sexuality appears preserved in 46,XX men, whereas it is impaired in women with MRKH syndrome before treatment. Although there is still a paucity of data on general health, bone and cardiometabolic effects, and mortality, it would appear that the 46,XX DSD condition is less severely affected than other DSD conditions. Further structured and continued multi-center follow-up is needed to provide more information on the long-term outcome of this very rare non-CAH 46,XX DSD condition.

Intersex Pretenders.

False claims of having an intersex condition have been observed in print, video, Internet media, and in live presentations. Claims of being intersexed in publicly accessible media were examined and evidence that they were false was considered sufficiently conclusive in 37 cases. Falsity was most often detected due to medical implausibility and/or inconsistency, but sometimes also using information from third-party or published sources. The majority, 26/37, of cases were natal males; 11/37 were natal females. Almost all (34/37) were transgendered, living, or aspiring to live, in their non-natal sex or as socially intergender. The most commonly claimed diagnosis was ovotesticular disorder ("true hermaphroditism") due to chimerism, an actually uncommon cause of authentic intersexuality. Motivations for pretending to be intersexed were inferred from statements and behaviors and were varied. Some such pretenders appear to be avoiding the external or internalized stigma of an actual transgendered condition. Some appear, similarly to persons with factitious disorder, to be seeking attention and/or the role of a sick, disadvantaged, or victimized person. Some showed evidence of paraphilia, most frequently autogynephilia, and, in several cases, paraphilic diaperism. For some cases, such claims had been accepted as authentic by journalists or social scientists and repeated as true in published material.

Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster.

Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvement of non-coding regulation in this process remains unclear. Here we show that the deletion of a single microRNA cluster, miR-17~92, induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayed in XY knockout gonads, which develop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.

Testicular differentiation in 46,XX DSD: an overview of genetic causes.

In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of SRY to the X chromosome or an autosome. In the absence of SRY, other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.

[Differences in sexual development-S2k guideline update]. / Varianten der Geschlechtsentwicklung ­ Aktualisierung der S2k-Leitlinie.

BACKGROUND: Human beings with a difference in sexual development (DSD) often underwent gender reassignment surgery during early childhood. However, the medical decision was often not congruent with the gender identity that affected persons developed later on. OBJECTIVES: To represent the interests of affected persons, an interdisciplinary guideline in cooperation with support groups was written. MATERIALS AND METHODS: The revision of the first version of the guideline, published in 2016, was edited by 18 professional societies and working groups as well as 3 support groups. A literature search was performed for each of the 12 chapters. Recommendations and statements created by the working groups were voted on during four consensus conferences. RESULTS: The guideline highlights the right of self-determination of affected persons. In this context, new legal requirements are reported. Other than necessary primary diagnostics, medical procedures should be postponed. Most important is the psychological support of parents and patients. Tumor risk of the gonads and protection of fertility are analyzed and discussed in detail. CONCLUSION: The content of the guideline represents a paradigm shift in dealing with human beings with a difference of sexual development. Projects as DSD Care and Empower-DSD help to promote the practical implementation of the guideline's recommendations.

[Genetic analysis for a female carrying idic(Y)(p11.32) with Disorders of sex development].

OBJECTIVE: To explore the genetic basis for a patient with Disorders of sex development (DSD). METHODS: A female patient who had presented at the Linyi People's Hospital due to primary amenorrhea on April 6, 2022 was selected as the study subject. Conventional chromosomal karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), fluorescence quantitative PCR and Sanger sequencing were carried out for the patient. RESULTS: The patient, a 14-year-old female, had featured short statue, multiple nevi, and primary amenorrhea. She was found to have a karyotype of 46,X,idic(Y)(p11.3)[59]/45,X[39]/47,X,idic(Y)(p11.3)×2[2]. The result of FISH assay was 46,X,der(Y).ish idic(Y)(p11.3)(SRY+)[59]/45,X[39]/47,X,der(Y)×2.ish idic(Y)(p11.3)(SRY+)[2]. That of CMA was arr[GRCh37](X)×1,(Y)×0-1,arr[GRCh37]Yp11.32(118552_472090)×1. The patient had no deletion in the AZF region of Y chromosome, and was negative for variant of SRY gene. Combining the above results, her molecular karyotype was determined as mos 46,X,idic(Y)(p11.32)[59]/45,X[39]/47,X,idic(Y)(p11.32)×2[2].ish 46,X,idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[59]/45,X(DXZ1+,DYZ1-,DYZ3-,SRY-)[39]/47,X,der(Y)×2.ish idic(Y)(p11.32)(DXZ1+,DYZ1++,DYZ3++,SRY+)[2].arr[GRCh37](X)×1, (Y)×0-1，arr[GRCh37]Yp11.32(118552_472090)×1. The patient was diagnosed with mosaicism DSD with idic(Y)(p11.32). CONCLUSION: The abnormal mosaicism karyotype probably underlay the DSD in this patient.

Recommendations for 46,XX Congenital Adrenal Hyperplasia Across Two Decades: Insights from the North American Differences of Sex Development Clinician Survey.

Several aspects of clinical management of 46,XX congenital adrenal hyperplasia (CAH) remain unsettled and controversial. The North American Disorders/Differences of Sex Development (DSD) Clinician Survey investigated changes, over the last two decades, in clinical recommendations by specialists involved in the management of newborns with DSD. Members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology participated in a web-based survey at three timepoints: 2003-2004 (T1, n = 432), 2010-2011 (T2, n = 441), and 2020 (T3, n = 272). Participants were presented with two clinical case scenarios-newborns with 46,XX CAH and either mild-to-moderate or severe genital masculinization-and asked for clinical recommendations. Across timepoints, most participants recommended rearing the newborn as a girl, that parents (in consultation with physicians) should make surgical decisions, performing early genitoplasty, and disclosing surgical history at younger ages. Several trends were identified: a small, but significant shift toward recommending a gender other than girl; recommending that adolescent patients serve as the genital surgery decision maker; performing genital surgery at later ages; and disclosing surgical details at younger ages. This is the first study assessing physician recommendations across two decades. Despite variability in the recommendations, most experts followed CAH clinical practice guidelines. The observation that some of the emerging trends do not align with expert opinion or empirical evidence should serve as both a cautionary note and a call for prospective studies examining patient outcomes associated with these changes.

Healthcare communication satisfaction and psychosocial outcomes in adolescents and young adults with differences of sex development.

OBJECTIVES: We examined: (1) healthcare communication satisfaction and psychosocial outcomes (resilience, QoL, and psychological adjustment) in adolescents and young adults (AYA) with differences of sex development (DSD), (2) differences in psychosocial outcomes between those who were highly satisfied and those who were less satisfied, and (3) group differences between adolescents (ages 12-17) and young adults (ages 18-26) regarding associations with healthcare communication and psychosocial outcomes. METHODS: AYA with DSD across four study sites reported on satisfaction with healthcare communication and psychosocial outcomes. Analyses included descriptive statistics (aim 1), independent samples t-tests (aim 2), and Pearson's correlations (aim 3). RESULTS: Participants reported high levels of satisfaction with healthcare communication. Higher healthcare communication satisfaction was associated with greater resilience (p = .01), better QoL (p = .02), and fewer internalizing problems (p = .04). For adolescents, higher healthcare communication satisfaction was associated with better psychosocial outcomes (p values ranging from.01-.04). No significant associations were found in the young adult group. CONCLUSIONS: Satisfaction with healthcare communication is related to positive psychosocial outcomes in adolescents with DSD. PRACTICE IMPLICATIONS: These data underscore the importance of optimizing communication with families, engaging AYA in early and ongoing discussions about their care, and including psychosocial providers in DSD care.

Cuerpos desgener[iz]ados: rescatando las experiencias de personas intersex como usuarias del sistema de salud público Chileno / Corpos desgener[iz]ados: resgatando as experiências de pessoas intersexuais como usuárias do sistema público de saúde chileno / Desgener[iz]ated bodies: rescuing the experiences of intersex people as users of the Chilean public health system

Introducción: La intersexualidad comprende condicionesinfrecuentes donde una persona nace con una anatomíasexual diferente del binario hombre-mujer; esto suponehabitar un cuerpo fuera de lo inteligible y estigmatizado.Históricamente, desde la heteronorma, el modelo biomédicoha buscado normalizarles quirúrgicamente para asignarprecoz y arbitrariamente un sexo-género armónico con lagenitalidad. Desde los Derechos Humanos, estas prácticasson cuestionadas por colectivos Intersex.Materiales y método: Estudio de caso, entre años 2019 y2020; técnica de entrevista en profundidad a dos usuariosadultos de los Policlínicos de Urología y Endocrinología de unhospital público en Santiago, Chile; se utilizó la fenomenologíade Husserl para comprender la experiencia en el sistema desalud de las personas intersex. El análisis de la informaciónse basó en la propuesta de Colaizzi.Resultados: Se reconocieron unidades de significado principalese imbricadas, cuyas esencias permitieron describir el fenómenode: ser niño y habitar el espacio hospitalario, vivir con lacondición actualmente, y la experiencia de utilizar el sistemade salud siendo adulto.Conclusiones: Se identificaron diversas estrategias de agenciatanto en el espacio hospitalario como el cotidiano, medianteun proceso personal y silencioso de aprendizajes sobre lasimplicancias de ser intersexual.(AU)

Introduction: Intersexuality includes extremely rareconditions where a person is born with a sexual anatomydifferent from the male-female binary; this supposesinhabiting a body outside the intelligible, configuringa stigma. Historically and from the heteronorm, thebiomedical model has sought to surgically normalizethem in order to precociously and arbitrarily assigna gender in harmony with genitality. From HumanRights, these practices have been questioned byIntersex groups.Materials and method: During the years 2019 and2020, case studies were carried out through in-depthinterviews with two adult users of the Urology andEndocrinology Polyclinics of a public hospital atSantiago, Chile; Husserl's phenomenology was usedto visualize the phenomenon according to how it isexperienced by the subjects who carry it, using theprocedure described by Colaizzi as an informationanalysis plan.Results: Main and overlapping units of meaning wererecognized, whose essences allowed describing thephenomenon of: being a child and inhabiting thehospital space, currently living with the condition,and the experience of using the health system as anadult, with new and own meanings.Conclusions: Various agency strategies were identifiedboth in the hospital space and in everyday life, througha personal and silent process of learning about theimplications of being intersex.(AU)

Introdução: Intersexo compreende condições rarasem que uma pessoa nasce com uma anatomia sexualdiferente do binário masculino-feminino; Isso significahabitar um corpo fora do que é inteligível e estigmatizado.Historicamente, a partir da heteronormação, o modelobiomédico buscou normalizá-los cirurgicamente paraatribuir precoce e arbitrariamente um sexo-gêneroharmônico com a genitalidade. A partir dos DireitosHumanos, essas práticas são questionadas por gruposintersexuais.Materiais e método: Estudo de caso, entre os anos de2019 e 2020; técnica de entrevista em profundidadecom dois usuários adultos das Policlínicas de Urologiae Endocrinologia de um hospital público de Santiago,Chile; A fenomenologia de Husserl foi utilizada paracompreender a experiência de pessoas intersexuaisno sistema de saúde. A análise das informações foibaseada na proposta de Colaizzi.Resultados: Reconheceram-se unidades de significadoprincipais e sobrepostas, cujas essências permitiramdescrever o fenômeno de: ser criança e habitar oespaço hospitalar, viver atualmente com a condição e aexperiência de usar o sistema de saúde na fase adulta.Conclusões: Foram identificadas várias estratégiasde agenciamento tanto no hospital como na vidaquotidiana, através de um processo pessoal e silenciosode aprendizagem sobre as implicações de ser intersexo.(AU)

Arguments for a ban on pediatric intersex surgery: A dis/analogy with Jehovah witness blood transfusion.

This article argues for a ban on the performance of medically unnecessary genital normalizing surgeries as part of assigning a binary sex/gender to infants with intersex conditions on the basis of autonomy, regardless of etiology. It does this via a dis/analogy with the classic case in bioethics of Jehovah Witness (JW) parents' inability to refuse life-saving blood transfusions for their minor children. Both cases address ethical medical practice in situations where parents are making irreversible medical decisions on the basis of values strongly held, identity, and relationship-shaping values-such as religious beliefs or beliefs regarding the inherent value of binary sex/gender-amidst ethical pluralism. Furthermore, it takes seriously-as we must in the intersex case-that the restriction of parents' right to choose will likely result in serious harms to potentially large percentage of patients, their families, and their larger communities. I address the objection that parents' capacity to choose is restricted in the JW case on the basis of the harm principle or a duty to nonmaleficence, given that the result of parent choice would be death. I provide evidence that this is mistaken from how we treat epistemic uncertainty in the JW case and from cases in which clinicians are ethically obligated to restrict the autonomy of nonminor patients. I conclude that we restrict the parents' right to choose in the JW case-and should in the case of pediatric intersex surgery-to secure patient's future autonomy.

Psychological support for individuals with differences of sex development (DSD).

OBJECTIVE: Congenital conditions with atypical development of chromosomal, gonadal, or anatomic sex characteristics are referred to as Differences of Sex Development (DSD). Psychosocial care is recommended to be an integral part of clinical management for individuals with DSD. Few studies have examined the perceived need for, utilization of and the opinions of individuals with DSD regarding psychological support. METHODS: This cross-sectional study was part of a European multicentre study in 14 different medical centres in six countries. In total, 1040 individuals with DSD participated in a patient-reported outcome questionnaire asking about experiences and opinions regarding psychological support in DSD care. RESULTS: A majority of the participants reported that they had not received psychological support, in childhood and/or adolescence (70.6%, n = 692) nor in adulthood (67.9%, n = 661). Need for psychological support in childhood and/or adolescence was reported by 51.3% (n = 503), need for psychological support in adulthood, was reported by 49.5% (n = 482). The majority (80.2%; n = 718) agreed with the statement that people with DSD should always be offered psychological support. According to 78.7% (n = 697) of the participants, parents of children with DSD should always be offered psychological support. CONCLUSION: Our findings support the existing consensus that psychological support should be an integral part of DSD care. The discrepancy between received and perceived need for psychological support suggests that individuals with DSD experience barriers to access mental health care services. Psychosocial and psychological services for children, adolescents and adults should therefore be available and offered throughout the lifespan to individuals with DSD.

Sex Reassignment Surgery, Marriage, and Reproductive Rights of Intersex and Transgender People in Sunni Islam.

The traditional gender binary constitutes an integral aspect of Islamic social ethics, which has a pivotal role in shaping religious obligations, legal proceedings, and interpersonal judgments within Muslim communities. Within the familial sphere, this gender binary underscores fundamental responsibilities encompassing parenthood, filial duties, and inheritance rights. Recent years have witnessed a growing challenge to the traditional concept of the gender binary within Islamic societies. This shift is driven by increasing social libertarianism that emphasizes gender fluidity and individual choice. Hence, this article aims to critically scrutinize evolving discussions and controversies about the rights of intersex and transgender individuals, particularly issues relating to sex reassignment or gender-affirming surgery, marriage, and reproduction, from the perspective of the Sunni tradition of Islam. To support the various interpretations and insights presented here, a comprehensive and rigorous analysis is carried out on various religious texts and scholarly sources to elucidate the theological and jurisprudential positions on gender issues. It is thus concluded that Shariah offers greater flexibility in the treatment of intersex individuals compared to those with gender dysphoria because the intersex condition is viewed as a physical impairment that is not the choice of the afflicted individual. By contrast, in the case of individuals with gender dysphoria, they are willfully attempting to change their recognized biological sex, that God had naturally given to them at birth. Therefore, it is recommended that such transgender individuals deserve respectful psychological and social rehabilitation with help and guidance from religious authorities, their families, and communities.

46,XX disorder of sex development associated with skin abnormalities due to homozygous R-Spondin 1 loss of function mutation.

A child, who was reared as male, presented in his early childhood to the endocrine clinic with penoscrotal hypospadias which was noticed at birth. On examination, he had both gonads in the scrotal sacs with complete scrotal fusion, rugosities and chordee with a single opening. He had increased palmoplantar skin desquamation. As an initial part of the workup, karyotyping was done, which was 46,XX. To rule out the most common cause of 46,XX disorder of sex development (DSD) in phenotypical males (SRY - Sex Determining Region Y gene - translocation), fluorescent in situ hybridisation for SRY was done, which was negative. Whole exome sequencing revealed a homozygous loss of function mutation in the R-Spondin1 gene. Here we report a rare case of 46,XX DSD with loss of function mutation in the R-Spondin1 gene associated with skin abnormalities.

Disorders of Sex Development: Experience at a Tertiary Care Hospital in Bangladesh.

In newborns, it is an emergency to decide the appropriate sex for rearing and eventual prevention associated metabolic disturbances. The birth of a baby with ambiguous genitalia inevitably precipitates a crisis for the baby and its family. This retrospective analysis of hospital data was designed to determine the chromosomal and etiological diagnosis of children presented with suspected disorders of sex development (DSD) according to the newer DSD consensus document. We retrospectively analyzed the available medical records of all patients admitted into the inpatient departments of Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh from January 2014 to December 2019, and all patients with the diagnosis of DSD in the hospital record were initially selected for the study. A total of 60 admitted cases with a disorder of sex development were classified according to the new DSD classification. 46XX DSD were 63.3% (n=38), 46XY DSD were 33.3% (n=20), sex chromosome DSD were 3.3% (n=2). Among 38 cases of 46XX DSD, the most common cause was congenital adrenal hyperplasia (97.0%, n=37), one was 46XX testicular DSD. However, among 46XY DSD cases, partial androgen insensitivity/5α-reductase deficiency (50.0%, n=10) was most common disorder. Other causes of 46XY DSD included congenital adrenal hyperplasia (20.0%, n=4), testosterone synthesis defect (20.0%, n=4), testicular regression syndrome (n=1) and persistent Mullerian duct syndrome (n=1). Sex chromosome disorders are mixed gonadal dysgenesis (n=1), chimeric ovotesticular DSD (n=1). In this study, 46XX DSD was the commonest of all, showing the predominance of congenital adrenal hyperplasia, especially salt-losing type. Early detection and prompt treatment may help reduce mortality and morbidity from these acute life-threatening conditions.

[Clinicopathological analysis of gonadal differentiation of sex development disorder].

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

One-stage surgical case management of a two-year-old Arabian horse affected by male-pseudo hermaphroditism.

A two-year-old Arabian horse presented for abnormal external genitalia and dangerous stallion-like behavior was diagnosed with disorder of sexual development (DSD), also known as intersex/hermaphroditism. Standing 1-stage surgical procedure performed under sedation, and local anesthesia to concurrently eliminate stallion-like behavior, risk of neoplastic transformation of intraabdominal gonads, and to replace ambiguous external genital with a functional, and cosmetically more acceptable anatomy. Step-1) Laparoscopic abdominal exploration and gonadectomy; Step-2) Rudimentary penis resection and perineal urethrostomy. The horse tolerated surgery well (combined surgery time 185 min) with no complications. At macroscopic examination of the gonads, they resembled hypoplastic testis-like tissues. Microscopic examination confirmed presence of seminiferous tubules, Leydig and Sertoli/granulosa cells. Cytogenetic evaluation revealed a 64,XX karyotype, SRY-negative. The stallion-like behavior subsided within days post-operatively. Long-term follow-up revealed the genitoplasty site healed without urine scalding or urethral stricture. The owner satisfaction was excellent and the horse could be used post-surgery as an athlete.

Sperm function is required for suppressing locomotor activity of C. elegans hermaphrodites.

Sex differences in sex-shared behavior are common across various species. During mating, males transfer sperm and seminal fluid to females, which can affect female behavior. Sperm can be stored in the female reproductive tract for extended periods of time and used to fertilize eggs. However, the role of either sperm or embryo production in regulating female behavior is poorly understood. In the androdioecious nematode C. elegans, hermaphrodites produce both oocytes and sperm, enabling them to self-fertilize or mate with males. Hermaphrodites exhibit less locomotor activity compared to males, indicating sex difference in behavioral regulation. In this study, mutants defective in the sperm production and function were examined to investigate the role of sperm function in the regulation of locomotor behavior. Infertile hermaphrodites exhibited increased locomotor activity, which was suppressed after mating with fertile males. The results suggest that sperm, seminal fluid, or the presence of embryos are detected by hermaphrodites, leading to a reduction in locomotor activity. Additionally, females of closely related gonochoristic species, C. remanei and C. brenneri, exhibited reduced locomotor activity after mating. The regulation of locomotion by sperm function may be an adaptive mechanism that enables hermaphrodites lacking sperm or embryo to search for mates and allow females to cease their search for mates after mating.