After given due consideration to the need of the original hyperandrogenic regulations and the constant pressure from society upon the International Association of Athletics Federation’s (hereafter IAAF) to take action against the presumed unfair competitive edge which such an athlete posed, it cannot be said that a female athlete’s natural levels of testosterone should be considered prejudicial in cases where such an excess is naturally produced within the athlete’s body. Any regulation that impedes upon the rights and freedoms of an athlete must be drafted in a manner that bears the highest degree of credibility and evidence, including the support of several cross-examinations of the evidential value before the promulgation thereof. The IAAF’s hyperandrogenic regulations fail to meet this extrinsic threshold and instead announces it in the absence of trailed and proven factual scientific evidence. The CAS board identified a lack of legality due to insufficient scientific evidence presented by the IAAF in order to justify the need of such regulations. This study found that Hyperandrogenic athletes faced numerous accounts of prejudice as a result of the regulations and the enforcement thereof by the IAAF. After the CAS panel established that several of the Hyperandrogenic athlete’s rights were infringed upon by the regulations, in an attempt to evade legal consequences, the IAAF withdrew the hyperandrogenic regulations leading to the abolishment of all legal proceedings linked thereto. The IAAF then retaliated months later with the publication of their DSD regulations. After facing an immense amount of critique by professionals globally, a communal consensus was reached that the DSD regulation was even weaker than its pre-successor. This study firstly investigates the scientific evidence, both in manner and in the hypothesis, presented by the IAAF in support of their DSD regulations. Secondly, it will criticise the legitimacy of the Bermon test and its publication in the British Journal of Sport Medicine (hereinafter the BJSM). Comparisons are made between hyperandrogenism and collateral cases involving similar medical conditions. Attention has also been drawn to the legal recourse currently available to affected athletes. Hereinafter, opinions and suggestions will be made as to an appropriate, and a law-abiding way as to how hyperandrogenism should be regulated. / Dissertation (LLM)--University of Pretoria, 2019. / Procedural Law / LLM (Research) / Unrestricted

No description available.

No description available.

This thesis explores some of the themes and issues that social workers may wish to consider when investigating and addressing matters pertaining to wellness in individuals with sex-variances. Foundational literature includes writings by John Money, the Chicago Consensus, and the clinical guidelines of the Intersex Society of North America. A three pillars model is introduced as a potential means for fostering better understanding and diversity in relation to sex, gender, and sexuality. Semi-structured interviews surrounding wellness are conducted with four individuals who have sex-variances. Interview results are analysed using Interpretative Phenomenological Analysis. Recommendations are put forth in a manner designed to allow social workers to work collaboratively with individuals who have sex-variances and their families, as well as with other medical and health professionals who provide services thereof. The analyses and recommendations presented in this thesis are situated within a context of evidence-based anti-oppressive practice.

Le développement du sexe est un processus fondamental et versatile qui forme la morphologie, la physiologie et le comportement des animaux. Le processus de développement sous-jacent est composé de la détermination et de la différentiation du sexe. Les mécanismes de détermination du sexe sont souvent génétiques et nommés gènes de détermination du sexe. A l’heure actuelle, parmi les gènes de détermination connus, trois familles de gènes nommément sox, dmrt and les facteurs TGF-ß gouvernent ce processus de développement.Comme exception à cette règle, sdY « sexually dimorphic on the Y » n’appartient à aucune de ces familles puisqu’il provient d’une duplication/évolution d’un gène ancestral de l’immunité, c’est-à-dire d’un facteur lié à l’interféron, irf9. sdY est le gène maître de la détermination du sexe chez les salmonidés, un groupe de poissons incluant des espèces tel que la truite arc-en-ciel et le saumon Altantique. L’étude présentée avait pour but de premièrement caractériser les propriétés de la protéine SdY. Deuxièment, l’étude a pour but de comprendre comment SdY pouvait entraîner la différentiation testiculaire. Les résultats pris dans leur ensemble proposent que SdY pourrait entraîner la différentiation testiculaire chez les salmonidés en interagissant avec un facteur prédominant de la voie femelle. / Sexual development is a fundamental and versatile process that shapes animal morphology, physiology and behavior. The underlying developmental process is composed of the sex determination and the sex differentiation. The initial triggers are often genetics called sex determining genes. To date, among the known sex determining genes, three gene families namely sox, dmrt and TGF-ß factors govern this developmental program. As exception to this rule, sdY “sexually dimorphic on the Y” does not belong to one of these families as it comes from the duplication / evolution of an ancestor gene related to immunity, i.e., the interferon related factor 9, irf9.sdY is the master sex determining gene in salmonids, a group of fishes that include species such as rainbow trout and Atlantic salmon. The present study was aimed to firstly characterize the features of SdY protein. Results indicate that SdY is predominantly localized in the cytoplasm, composed of a ß-sandwich core surrounded by three a-helices as well specific characteristics conferring a putative protein-protein interaction site. Secondly, the study was aimed to understand how SdY could trigger testicular differentiation. Altogether results propose that SdY would trigger testicular differentiation in salmonids by interacting with a prominent female factor.

O distúrbio da diferenciação sexual que resulta em ambiguidade genital na criança, denominado atualmente de Anomalias da Diferenciação Sexual (ADS), tem se constituído como um problema e um desafio aos profissionais que tratam desses casos. Apesar de existir um número considerável de estudos sobre o tema, ainda não há um consenso sobre sua extensão, manejo e repercussões para os pacientes e seus pais. Este estudo buscou investigar as representações de mães e pais, de crianças com ADS, sobre a identidade de gênero de seus filhos. Foram entrevistados 3 mães e 3 pais de filhos nascidos com ADS, de diferentes idades. A entrevista narrativa e a análise de conteúdo foram utilizadas, respectivamente, como forma de coleta e análise dos dados. Os resultados mostraram que, tanto mães quanto pais, atribuem fundamental importância à anatomia da genitália como critério para definição da identidade sexual da criança, base sobre a qual se constitui, ao longo de seu desenvolvimento, a identidade de gênero da mesma. O estudo também possibilitou o levantamento e discussão de outros aspectos considerados importantes na opinião das mães e dos pais entrevistados como, por exemplo, o impacto emocional do diagnóstico quando do nascimento da criança, a investigação etiológica, o tratamento da ADS, o manejo médico e questões acerca do futuro dos filhos com ADS, que foram discutidos na pesquisa. / The disorders of sexual diferentiation which result from genital ambiguity in children, nowadays called Disorders of Sex Development (DSD), have become a problem and a challenge for the professional team who deals with these cases. Besides a large number of articles about this issue, there is no consensus about its extension, management and repercussion for patients and their parents. This study investigated the representations of gender identity of mothers and fathers of children with DSD. Three mothers and three fathers of children of different ages with DSD were interviewed. Narrative Interview and Content Analysis were used, respectively, as procedures of data collection and data analysis. The results showed that both mothers and fathers assigned fundamental importance to the genital anatomy as a criterion for sexual identity definition based on which gender identity will develop. In addition, this study also highlighted others aspects considered as important by the interviewed parents, such as the emotional impact of the diagnosis at birth and during the etiological investigation and treatment, the medical management, and issues about their children with DSD future.

O distúrbio da diferenciação sexual que resulta em ambiguidade genital na criança, denominado atualmente de Anomalias da Diferenciação Sexual (ADS), tem se constituído como um problema e um desafio aos profissionais que tratam desses casos. Apesar de existir um número considerável de estudos sobre o tema, ainda não há um consenso sobre sua extensão, manejo e repercussões para os pacientes e seus pais. Este estudo buscou investigar as representações de mães e pais, de crianças com ADS, sobre a identidade de gênero de seus filhos. Foram entrevistados 3 mães e 3 pais de filhos nascidos com ADS, de diferentes idades. A entrevista narrativa e a análise de conteúdo foram utilizadas, respectivamente, como forma de coleta e análise dos dados. Os resultados mostraram que, tanto mães quanto pais, atribuem fundamental importância à anatomia da genitália como critério para definição da identidade sexual da criança, base sobre a qual se constitui, ao longo de seu desenvolvimento, a identidade de gênero da mesma. O estudo também possibilitou o levantamento e discussão de outros aspectos considerados importantes na opinião das mães e dos pais entrevistados como, por exemplo, o impacto emocional do diagnóstico quando do nascimento da criança, a investigação etiológica, o tratamento da ADS, o manejo médico e questões acerca do futuro dos filhos com ADS, que foram discutidos na pesquisa. / The disorders of sexual diferentiation which result from genital ambiguity in children, nowadays called Disorders of Sex Development (DSD), have become a problem and a challenge for the professional team who deals with these cases. Besides a large number of articles about this issue, there is no consensus about its extension, management and repercussion for patients and their parents. This study investigated the representations of gender identity of mothers and fathers of children with DSD. Three mothers and three fathers of children of different ages with DSD were interviewed. Narrative Interview and Content Analysis were used, respectively, as procedures of data collection and data analysis. The results showed that both mothers and fathers assigned fundamental importance to the genital anatomy as a criterion for sexual identity definition based on which gender identity will develop. In addition, this study also highlighted others aspects considered as important by the interviewed parents, such as the emotional impact of the diagnosis at birth and during the etiological investigation and treatment, the medical management, and issues about their children with DSD future.

O distúrbio da diferenciação sexual que resulta em ambiguidade genital na criança, denominado atualmente de Anomalias da Diferenciação Sexual (ADS), tem se constituído como um problema e um desafio aos profissionais que tratam desses casos. Apesar de existir um número considerável de estudos sobre o tema, ainda não há um consenso sobre sua extensão, manejo e repercussões para os pacientes e seus pais. Este estudo buscou investigar as representações de mães e pais, de crianças com ADS, sobre a identidade de gênero de seus filhos. Foram entrevistados 3 mães e 3 pais de filhos nascidos com ADS, de diferentes idades. A entrevista narrativa e a análise de conteúdo foram utilizadas, respectivamente, como forma de coleta e análise dos dados. Os resultados mostraram que, tanto mães quanto pais, atribuem fundamental importância à anatomia da genitália como critério para definição da identidade sexual da criança, base sobre a qual se constitui, ao longo de seu desenvolvimento, a identidade de gênero da mesma. O estudo também possibilitou o levantamento e discussão de outros aspectos considerados importantes na opinião das mães e dos pais entrevistados como, por exemplo, o impacto emocional do diagnóstico quando do nascimento da criança, a investigação etiológica, o tratamento da ADS, o manejo médico e questões acerca do futuro dos filhos com ADS, que foram discutidos na pesquisa. / The disorders of sexual diferentiation which result from genital ambiguity in children, nowadays called Disorders of Sex Development (DSD), have become a problem and a challenge for the professional team who deals with these cases. Besides a large number of articles about this issue, there is no consensus about its extension, management and repercussion for patients and their parents. This study investigated the representations of gender identity of mothers and fathers of children with DSD. Three mothers and three fathers of children of different ages with DSD were interviewed. Narrative Interview and Content Analysis were used, respectively, as procedures of data collection and data analysis. The results showed that both mothers and fathers assigned fundamental importance to the genital anatomy as a criterion for sexual identity definition based on which gender identity will develop. In addition, this study also highlighted others aspects considered as important by the interviewed parents, such as the emotional impact of the diagnosis at birth and during the etiological investigation and treatment, the medical management, and issues about their children with DSD future.

Orientadores: Andréa Trevas Maciel-Guerra, Vera Lúcia Gil da Silva Lopes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T23:41:30Z (GMT). No. of bitstreams: 1 Latuf_JulianadePaulo_M.pdf: 2398402 bytes, checksum: cbd1c5c98ab12541607b0be2b5ca8120 (MD5) Previous issue date: 2013 / Resumo: Quadros de ambiguidade genital e esterilidade com cariótipo 46,XY podem ser devidos a mosaico com linhagem 45,X não detectável no cariótipo em linfócitos de sangue periférico. Quando essa linhagem não é detectada, esses indivíduos deixam de ser investigados em relação a uma série de problemas clínicos. Este trabalho teve como objetivo verificar se a hibridação in situ com fluorescência (FISH) em células de mucosa oral poderia ser empregada para detectar criptomosaicismo com linhagem 45,X em indivíduos com cariótipo 46,XY. A casuística foi composta por 19 homens saudáveis com idades entre 20 e 30 anos e cinco pacientes com distúrbios da diferenciação do sexo (DDS) com idades entre 5 e 23 anos, quatro com mosaico 45,X/46,XY e um com disgenesia testicular 46,XY associada a déficit de crescimento. Após confirmar que os jovens saudáveis tinham cariótipo 46,XY em 50 metáfases de linfócitos de sangue periférico, foi realizada análise por FISH com sondas específicas para os cromossomos X e Y em 1.000 núcleos interfásicos de linfócitos de sangue periférico e 1.000 de mucosa oral, seguida de comparação da proporção de núcleos contendo apenas o sinal do cromossomo X nos dois tecidos. A mesma análise foi feita nos cinco pacientes com DDS. A distribuição da proporção dos núcleos interfásicos de linfócitos e mucosa oral contendo apenas o sinal do X nos jovens saudáveis foi compatível com a distribuição normal, e número superior a 12:1.000 em linfócitos e 13:1.000 em mucosa oral devem ser considerados indicativos de mosaicismo em nosso laboratório. A frequência desses núcleos nos dois tecidos não diferiu significativamente (p=0,6855). Nos cinco pacientes com DDS a frequência de núcleos contendo apenas o sinal do X diferiu significativamente da observada em indivíduos normais em linfócitos (p=0,0008) e mucosa oral (p=0,0008). No paciente com cariótipo prévio 46,XY a linhagem 45,X foi confirmada por FISH em metáfases, e em um dos casos de mosaicismo foram detectadas linhagens celulares adicionais. Também não houve diferença significativa entre a frequência de núcleos contendo apenas o sinal do X nos dois tecidos desses pacientes (p=0,3750). Estes resultados indicam que a pesquisa de mosaicismo com linhagem 45,X em indivíduos com DDS ou esterilidade e cariótipo 46,XY pode ser feita por meio de FISH em mucosa oral, com vantagens evidentes em termos de custo e rapidez, além de ser feita a partir de tecido obtido de modo não invasivo / Abstract: Ambiguous genitalia and sterility with a 46,XY karyotype may be due to mosaicism with a 45, X karyotype not detectable in peripheral blood lymphocytes. When this cell line is not detected, these individuals fail to be investigated over a range of clinical problems. This study aimed to verify whether fluorescence in situ hybridization (FISH) in cells from buccal smear could be employed to detect cryptomosaicism with a 45,X cell line in individuals with a 46,XY karyotype. The sample consisted of 19 healthy men aged 20 to 30 years and five patients with disorders of sex development (DSD) aged 5 to 23 years, four with mosaicism 45,X/46,XY and one with testicular dysgenesis 46, XY associated with growth deficiency. After confirming that the healthy young men had a 46,XY karyotype in 50 metaphases from peripheral blood lymphocytes, FISH analysis with probes specific for chromosomes X and Y was done in 1,000 nuclei from peripheral blood lymphocytes and 1,000 from buccal smear, followed by comparison of the proportion of nuclei containing only the signal of the X chromosome in these tissues. The same analysis was performed in five patients with DDS. The distribution of the proportion of interphase nuclei of lymphocytes and buccal smear containing only the X signal in healthy young was consistent with normal distribution; a number greater than 12:1,000 in lymphocytes and 13:1,000 in buccal smear should be considered indicative of mosaicism in our laboratory. The frequency of these nuclei in both tissues did not differ significantly (p = 0.6855). In patients with DDS the frequency of nuclei containing only the X signal differed significantly from that observed in normal individuals both in lymphocytes (p = 0.0008) and buccal smear (p = 0.0008). In the patient with a prior 46,XY karyotype, a 45,X cell line was confirmed by FISH in metaphases, and in one case of mosaicism additional cell lines were detected. There was also no significant difference between the frequency of nuclei containing only the X signal in the two tissues of these patients (p = 0.3750). These results indicate that investigation of mosaicism with 45,X cell line in individuals with 46,XY DSD or sterility can be done by FISH in cells from buccal smear, with obvious advantages in terms of cost and speed, using a tissue obtained noninvasively / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas

Les anomalies du développement sexuel recouvrent un spectre phénotypique large. Les hommes XX présentent dans la majorité des cas un développement testiculaire normal, lié à la présence SRY sur un des chromosomes X. Dans 10% des cas, aucune cause n’est retrouvée. Chez les femmes, l’origine de l’insuffisance ovarienne prématurée (IOP) n’est identifiée que dans 20% des cas. L’objectif de cette thèse a été d’identifier de nouveaux mécanismes moléculaires impliqués dans le développement gonadique, testiculaire et ovarien, ainsi que dans son fonctionnement. L’étude d’une cohorte de patients DSD 46,XX SRY négatifs a mis en évidence une duplication de la région RevSex dans un désert génique en amont de SOX9 chez quatre patients. Ceci a permis de redéfinir la région minimale impliquée dans l'activation de l'expression de SOX9 à une taille maximale de 41.9 kb et de proposer un mécanisme permettant cette expression chez des hommes XX. Le séquençage d’exome chez dix patients de la cohorte n’a pas mis en évidence de mutations dans des gènes d’intérêts. L’ensemble de ces résultats pose la question du rôle des régions régulatrices dans la survenue des DSD.L’analyse d’une cohorte de patientes ayant une IOP a permis d'identifier des délétions incluant le gène CPEB1. Des études précédentes chez la souris ont montré son implication dans le développement folliculaire. Le séquençage du gène CPEB1 dans la cohorte n'a pas mis en évidence de mutation pathogène. Ce travail a permis de montrer que la délétion impliquant le gène CPEB1est une cause rare mais récurrente d'IOP et concerne environ 1% des patientes. Une microdélétion contenant le gène CASP3 un gène de la voie des caspases impliquée dans la régulation du pool folliculaire a également été identifiée chez une patiente. L'ensemble de ces résultats montre l'intérêt de l'étude génétique des patients présentant une anomalie du développement de la gonade ou de son fonctionnement par des techniques d'étude globale du génome. / Disorders of Sex Development (DSD) can be identified in new-born and during infancy but also in adults because of infertility. Most 46,XX testicular DSD have a normal testicular development due to the presence of the SRY gene at the tip of one of their X chromosome. However, the genetic causes of 46,XX-SRY negative testicular DSD remain poorly defined. In women, disorders of gonadal development can be responsible for primary ovarian insufficiency (POI) and genetic causes are identify in only 20% of cases. The aim of this thesis was to identify molecular mechanisms involved in gonadal development and in its functioning. The cohort study of 46,XX testicular DSD identified four patients with a duplication in the previously reported RevSex region located about 550 kb upstream of SOX9. One duplication allowed us to refine the minimal region associated with 46,XX-SRY negative DSD to a 40.7–41.9 kb element. Exome sequencing of 10 patients from the cohort did not show any mutation in genes implicated in DSD or in new candidate genes. These results raise questions about the role of the regulatory sequences in the onset of DSD.The cohort study of POI patients identified three patients carrying a microdeletion including CPEB1 a good candidate gene for POI as study in mice showed the implication of CPEB1 in follicular development. Sequencing CPEB1 gene did not identified any mutation. Therefore, heterozygous deletion of CPEB1 gene leading to haploinsufficiency could be responsible for POI in humans. This microdeletion is rare but recurrent and was identified in about 1% of patients with POI. Another microdeletion containing CASP3 gene that belongs to the caspase family, which is implicated in the regulation of the follicular pool, was identified in a patient. Further studies are needed to confirm the role of CASP3 in POI. These results demonstrate the importance of genetic study of patients presenting with DSD or POI using whole genome techniques.