Sexual Development最新文献

{"title":"One-Step Leaping Evolution from an Autosomal Pair to the Heteromorphic Sex Chromosomes.","authors":"Ikuo Miura, Foyez Shams, Tariq Ezaz, Mitsuaki Ogata","doi":"10.1159/000542537","DOIUrl":"10.1159/000542537","url":null,"abstract":"<p><strong>Background: </strong>Sex chromosomes evolve from an autosomal pair after the acquisition of a sex-determining gene. The primary sex chromosomes are homomorphic in both sexes and often undergo heteromorphism in either sex (XY in males or ZW in females) in association with chromosome rearrangements such as inversion, which creates a non-recombining region, called a stratum. Then, multiple strata may form by sequential inversions and extend the non-recombining region, where gene divergence accelerates, and degeneration of the Y or W chromosome progressively occurs.</p><p><strong>Summary: </strong>In contrast to the conventional theory, we propose a shortcut in heteromorphic sex chromosome evolution, where an autosomal pair directly evolves into a heteromorphic sex chromosome pair. We illustrate this with two frog cases where Y chromosome or autosome, which is morphologically inverted, was introgressed from another species through interspecific hybridization, instantly forming a new heteromorphic sex chromosome pair. This event resulted in a distinct non-recombining region immediately after hybridization.</p><p><strong>Key messages: </strong>The introduction of an inverted chromosome from a different species may be associated with benefits in morphology, breeding behavior, hybrid viability, sex determination, and recovery of the sex ratio of the hybrids. We discuss the molecular mechanisms driving preferential mutations in the introduced, inverted chromosome through interspecific hybridization.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"1-9"},"PeriodicalIF":2.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Testicular Descent: Recent Findings and Future Prospects in Canine Cryptorchidism.","authors":"Paulina Krzeminska","doi":"10.1159/000542245","DOIUrl":"10.1159/000542245","url":null,"abstract":"<p><strong>Background: </strong>Canine cryptorchidism, manifested by an abnormal testicular position, poses significant health risks and reproductive challenges in affected males. Despite a high prevalence, estimated at up to 10% in the canine population, a comprehensive understanding of its pathogenesis remains elusive. Studies in human cryptorchids and knockout mice have identified key factors involved in testicular descent, including INSL3, RXFP2, and AR. To date, only three DNA variants, found in the RXFP2, HMGA2, and KAT6A genes, have been associated with canine cryptorchidism.</p><p><strong>Summary: </strong>This review briefly summarizes current knowledge on testicular descent and the factors that regulate this process, based on cryptorchidism in humans and mice. It also highlights recent findings related to canine cryptorchidism, focusing on the INSL3, HMGA2, and KAT6A genes. The most significant results are discussed, with an emphasis on the role of the epididymis in testicular descent. This report presents insights that may facilitate further research aiming to broaden our understanding of canine cryptorchidism pathogenesis.</p><p><strong>Key messages: </strong>DNA polymorphism in the KAT6A gene, associated with changes in global H3K9 acetylation, as well as the DNA methylation pattern in the INSL3 gene, suggest that further research should strongly focus on epigenetic modifications. In addition, the development of the epididymo-testicular junction and the link between cryptorchidism prevalence and dog size should be further investigated.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"1-13"},"PeriodicalIF":2.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting p38α and -β MAPK Affects Testis Development in the Marsupial Tammar Wallaby.","authors":"Monika R Paranjpe, Patrick G S Grady, Hongshi Yu, Andrew J Pask, Rachel J O'Neill, Geoff Shaw, Marilyn B Renfree","doi":"10.1159/000541896","DOIUrl":"10.1159/000541896","url":null,"abstract":"<p><strong>Introduction: </strong>The MAPK genes are critical for gonadal differentiation in eutherian mammals, but their role in marsupial mammals is unknown. Characterisation and phylogenetic analyses of the tammar wallaby MAPK genes show these genes are highly conserved with their orthologues in mammalian and non-mammalian species.</p><p><strong>Methods: </strong>We cultured sexually indifferent tammar gonads in the presence of p38α and -β MAPK inhibitor, SB202190.</p><p><strong>Results: </strong>SB202190 downregulated SOX9 and AMH levels in XY-treated gonads when compared to controls, similar to the effects of oestrogen on the MAPK pathway in males. In contrast, XX gonads treated with the SB202190 inhibitor showed no change in mRNA expression between the control and treated gonads for any of the markers tested.</p><p><strong>Conclusions: </strong>This study confirms that components of the MAPK pathway drive testis differentiation via the key downstream genes SOX9 and AMH in marsupials as is observed in eutherian mammals.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"1-15"},"PeriodicalIF":2.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal Hydrocolpos in Bardet-Biedl Syndrome due to a Novel Frameshift Indel in the BBS10 Gene.","authors":"Maria Helena Palma Sircili, Rafael Loch Batista, Enoch Quindere de Sá Barreto, Solange Paiva Bueno, Anna Flávia Figueredo Benedetti, Flora Ladeira Craveiro, Raquel Matinez Ramos, Marcelo Praxedes Monteiro Filho, Sorahia Domenice, Berenice Bilharinho Mendonca, Francisco Tibor Dénes","doi":"10.1159/000541137","DOIUrl":"10.1159/000541137","url":null,"abstract":"<p><strong>Introduction: </strong>Hydrocolpos, a rare condition characterized by cystic dilatation of the vagina, can arise from various etiologies, including isolated imperforate hymen and vaginal atresia. Genetic conditions, such as Bardet-Biedl syndrome (BBS), may also manifest with hydrocolpos as part of urogenital malformations.</p><p><strong>Methods: </strong>We present a case of neonatal hydrocolpos associated with BBS. Sequencing of 19 BBS genes was performed to elucidate the genetic basis of the syndrome.</p><p><strong>Results: </strong>Genetic analysis revealed a novel frameshift indel variant (c.1543_1546dup p.Thr516Argfs*7) in the BBS10 gene. This finding expands the spectrum of BBS mutations and underscores the importance of genetic evaluation in patients with hydrocolpos, particularly when associated with additional clinical features suggestive of syndromic etiology.</p><p><strong>Conclusion: </strong>Pediatric urologists should maintain a high index of suspicion for underlying genetic conditions, including BBS, in neonates presenting with hydrocolpos, given the potential for more severe associated complications such as renal and retinal diseases, obesity, and polydactyly.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"1-6"},"PeriodicalIF":2.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prelims","authors":"","doi":"10.1159/000534834","DOIUrl":"https://doi.org/10.1159/000534834","url":null,"abstract":"","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":"92 1","pages":"67 - 70"},"PeriodicalIF":2.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"","doi":"10.1159/000529654","DOIUrl":"https://doi.org/10.1159/000529654","url":null,"abstract":"","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":"16 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49593078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare Case of a Turner Syndrome Patient with Metastatic Dysgerminoma and No Y-Chromosomal Material with Pathogenic Variants Found in KIT and MTOR.","authors":"Camilla Mains Balle, Christine Gaasdal Kassentoft, Jolinda Iris van Heusden, Michael Knudsen, Line Raaby, Claus Højbjerg Gravholt","doi":"10.1159/000536236","DOIUrl":"10.1159/000536236","url":null,"abstract":"<p><strong>Introduction: </strong>The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations thereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for the malignant transformation of gonadoblastoma in the dysgenetic gonad.</p><p><strong>Methods: </strong>We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of the tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants.</p><p><strong>Results: </strong>No Y-chromosomal material was detected in either tumor or blood. Whole exome-sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis 7 months after the initial diagnosis.</p><p><strong>Conclusion: </strong>Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomal material. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"203-210"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons Learned from 17 Years of Multidisciplinary Care for Differences of Sex Development Patients at a Single Indonesian Center.","authors":"Sultana M H Faradz, Nurin Listyasari, Agustini Utari, Mahayu Dewi Ariani, Achmad Zulfa Juniarto, Ardy Santosa, Annastasia Ediati, Tuula K Rinne, Dineke Westra, Hedi Claahsen-van der Grinten, Frank H de Jong, Stenvert L S Drop, Katie Ayers, Andrew Sinclair","doi":"10.1159/000534085","DOIUrl":"10.1159/000534085","url":null,"abstract":"<p><strong>Background: </strong>Our multidisciplinary team (MDT) is a large specialized team based in Semarang, Indonesia, that cares for a wide variety of pediatric and adult individuals with differences of sex development (DSD) from across Indonesia. Here, we describe our work over the last 17 years.</p><p><strong>Methods: </strong>We analyzed phenotypic, hormonal, and genetic findings from clinical records for all patients referred to our MDT during the period 2004-2020.</p><p><strong>Results: </strong>Among 1,184 DSD patients, 10% had sex chromosome DSD, 67% had 46,XY DSD, and 23% had 46,XX DSD. The most common sex chromosome anomaly was Turner syndrome (45,X) (55 cases). For patients with 46,XY DSD under-masculinization was the most common diagnosis (311 cases), and for 46,XX DSD, a defect of Müllerian development was most common (131 cases) followed by congenital adrenal hyperplasia (CAH) (116 cases). Sanger sequencing, MLPA, and targeted gene sequencing of 257 patients with 46,XY DSD found likely causative variants in 21% (55 cases), with 13 diagnostic genes implicated. The most affected gene codes for the androgen receptor. Molecular analysis identified a diagnosis for 69 of 116 patients with CAH, with 62 carrying variants in CYP21A2 including four novel variants, and 7 patients carrying variants in CYP11B1. In many cases, these genetic diagnoses influenced the clinical management of patients and their families.</p><p><strong>Conclusions: </strong>Our work has highlighted the occurrence of different DSDs in Indonesia. By applying sequencing technologies as part of our clinical care, we have delivered a number of genetic diagnoses and identified novel pathogenic variants in some genes, which may be clinically specific to Indonesia. Genetics can inform many aspects of DSD clinical management, and while many of our patients remain undiagnosed, we hope that future testing may provide answers for even more.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"170-180"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Novel Heterozygous Variants in RecA2 Domain of DHX37 Cause 46,XY Gonadal Dysgenesis and Testicular Regression Syndrome.","authors":"Hao Yang, Xiuqi Ma, Hongjuan Tian, Jinna Yuan, Dehua Wu, Guanping Dong, Qian Liu, Junfen Fu","doi":"10.1159/000534086","DOIUrl":"10.1159/000534086","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenic variants in DEAH-box RNA helicase DHX37 are one of the major causes of 46,XY gonadal dysgenesis and testicular regression syndrome (TRS). To date, only 13 different missense variants have been reported. We report two additional cases with different clinical presentations carrying two novel variants in the DHX37 gene.</p><p><strong>Case presentation and results: </strong>Case 1 (4.4-year-old boy) presented with significant micropenis and cryptorchidism and was diagnosed as TRS. Case 2 (13.5-year-old girl) had a 46,XY karyotype with female external genitalia and was diagnosed as GD. Two novel DHX37 variants affecting the RecA2 domain, p.G478R and p.L627F, were identified in these cases. Both variants identified in the probands were also present in their unaffected mother.</p><p><strong>Conclusion: </strong>Our findings broaden the variant spectrum of DHX37 in 46,XY differences of sex development (DSD) individuals.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":" ","pages":"198-202"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts of the 11th I-DSD Symposium.","authors":"","doi":"10.1159/000539511","DOIUrl":"https://doi.org/10.1159/000539511","url":null,"abstract":"<p><p>Abstracts of the 11th I-DSD Symposium.</p>","PeriodicalId":49536,"journal":{"name":"Sexual Development","volume":"17 Suppl 1 ","pages":"1-123"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}