Sexual Development最新文献

Introduction: The transcription factors Forkhead Box L2 (FOXL2) and SRY-Box Transcription Factor 9 (SOX9), among others, are required for embryonic ovarian and testicular differentiation, respectively. In patients with complete androgen insensitivity syndrome (CAIS), the testes are usually undescended and may show histological changes similar to those sometimes seen in patients with undescended testes (UDT). The aim of this study was to explore the expression of FOXL2 and SOX9 in testes from patients with CAIS and UDT.

Methods: Immunohistochemical staining with FOXL2 and SOX9 was performed on samples from 13 patients with CAIS and 20 with UDT.

Results: In addition to nuclear SOX9 expression in intratubular Sertoli cells, FOXL2 expression was present in stromal cells in eight of nine patients with CAIS and in one of 20 with UDT. Moreover, FOXL2 expression was found in the rete testis in three of nine samples that included this region.

Conclusion: Expression of the ovarian-specific marker FOXL2 in regions of the testes of patients with CAIS and UDT has not previously been documented and suggests partial activation of the female pathway within these testes. Further research is needed, including FOXL2 protein expression studies in larger series, and molecular studies, e.g. transcriptome analysis, to understand the pathophysiology and clinical significance of these novel findings.

Background Sexual size dimorphism (SSD), i.e., size difference between sexes, is common in fishes and spans from negligible to extreme body size differences, with both female‑ and male‑biased directions. While evolutionary drivers behind SSD such as sexual selection, fecundity selection and natural selection are increasingly well understood, our understanding of the underlying mechanisms of how sex‑specific growth trajectories develop is less clear. Summary Here we review recent findings of such mechanisms in fishes and reveal that SSD arises from an interplay of sex-linked and autosomal genetic factors. In teleosts, master sex-determining genes and growth regulators such as dmrt1/dmY, sdY, amhr2by, gdf6Y and gsdfY play key roles, while quantitative trait loci (QTL) influence growth and maturation, further contributing to SSD. Essential sex-specific regulation of hormones across brain, pituitary, liver and gonad determines SSD directionality. Epigenetic mechanisms, such as DNA methylation and non-coding RNA further modulate gene expression in growth and reproductive pathways. We identify the basic mechanisms, highlight knowledge gaps, and propose that multi-omics approaches can disentangle sex effects from dimorphism-specific regulation, linking together endocrine, genetic and epigenetic drivers. Key Messages 1. At the mechanistic level, SSD results from an interplay of genetic, endocrine and environmental influences. 2. Sex chromosomes and autosomal loci form the genetic architecture that shapes growth differences between males and females. 3. The somatotropic axis, involving GH/IGF signaling, together with the actions of sex steroids, serves as a central effector system underlying SSD in fish. 4. Epigenetic mechanisms help establish and maintain sex-specific gene expression programs, but integrative multi‑omic approaches are needed to uncover causal relationships and phenotypic plasticity in SSD.

Background: The management of 46,XY DSD is challenging due to genetic heterogeneity and phenotypic variability. This study aimed to characterize the clinical and genetic findings in patients with 46,XY DSD, using a targeted NGS panel for molecular evaluation.

Methods: A targeted DSD gene panel covering 31 genes was applied in 112 patients with nonsyndromic 46, XY DSD. Forty-six patients had previously tested negative for AR and SRD5A2 by Sanger sequencing. Patients were clinically categorized into disorders of gonadal development, androgen synthesis or action. Variant classification was performed according to the ACMG criteria.

Results: Among the 38 variants detected, 32 were pathogenic or likely pathogenic. Nineteen variants (50%) were novel. A molecular diagnosis was established in 31 patients (27.7%) and inclusion of previously diagnosed cases would have increased the overall diagnostic yield to 43.8%. The HSD17B3 variants were the most common, followed by NR5A1and LHCGR. In eight patients, the genetic findings led to reclassification of their clinical diagnosis, particularly in those initially suspected to have a disorder of androgen action.

Conclusion: NGS is a valuable diagnostic tool in the evaluation of 46,XY DSD, offering improved diagnostic yield. For patients without molecular diagnosis, more comprehensive genomic analyses, including non-coding regions, are required.

Introduction: The Y chromosome-linked gene sult1st6y (a homolog of the estrogen sulfotransferase gene) has recently been identified in Thunnus, a genus characterized by an XX/XY sex determination system. This study examined whether sult1st6y is a sex-determining gene in bluefin tuna (Thunnus orientalis).

Methods: The expression of sult1st6y was examined using polymerase chain reaction analyses and in situ hybridization. Sult1st6y expression in masculinized XX testes produced by aromatase inhibitor administration and the expression profile of the sult1st6y mutant, which was produced using CRISPR/Cas9, were examined.

Results: Sult1st6y was specifically expressed in XY gonads during sex differentiation. The onset of sult1st6y expression preceded that of other genes promoting sex differentiation. Sult1st6y expression was not detected in masculinized XX testes, indicating that gonads can differentiate into testes without sult1st6y if estrogens are depleted. The Sult1st6y mutant XY gonad showed a gene expression pattern similar to that of wild-type XX gonads.

Conclusion: Our results collectively suggest that sult1st6y is at the top of the molecular cascade that regulates gonadal sex differentiation. Sult1st6y may trigger testicular differentiation by deactivating estrogens, although its biochemical activity should be examined. This study provides evidence that sult1st6y is a major candidate sex-determining gene in tuna.

In the article "Sexual Dimorphic Expression of Dmrt1 in Adult Japanese Gecko (Gekko japonicus)" [Sex Dev. 2025;19(1-6):39-50; https://doi.org/10.1159/000548987] by Ping et al., the 1st author's name should correctly read "Jun Ping."

Introduction: Previous research has shown substantial variation in sexual dimorphism of facial structure and skin color across human populations. This study investigates sexual dimorphism in both facial shape and skin color in understudied populations from the Horn of Africa - Somalis and Ethiopians - focusing on the relationship between facial morphology and pigmentation traits.

Methods: Standardized frontal and profile photographs were collected from participants and analyzed using geometric morphometrics. Sexual shape dimorphism (SShD) was calculated by projecting each individual's facial shape onto a vector connecting average male and female shapes in Procrustes-aligned morphospace; higher values indicate more masculine morphology. Sexual color dimorphism (SCoD) was computed similarly, by projecting individual skin color values (from forehead and cheeks) onto a vector defined by average male-female difference in the CIE Lab* color space. Trajectory analysis and Bayesian hierarchical modelling were performed to examine associations between SShD and SCoD.

Results: Significant sexual dimorphism was detected in both facial shape and skin color across both populations. Male faces tended to be more robust and darker, while female faces were more gracile and lighter-skinned. However, despite group-level sex differences, individual-level associations between facial structure and skin pigmentation were weak or absent. Somali participants exhibited greater dimorphism in skin color compared to Ethiopians, while facial shape dimorphism remained consistent between groups.

Conclusion: Both target populations revealed significant sexual dimorphism in both structural and pigmentation facial traits. However, in contrast to previous findings reported in certain West African populations, we found no statistically reliable association between these two traits at the individual level. This decoupling may indicate distinct evolutionary or ecological pressures shaping morphological and pigmentation traits. Our findings suggest that no universal trade-off or consistent relationship exists between morphological and pigmentation components of sexual dimorphism across human populations.

Introduction: Sexual conflict is pervasive and can favor the evolution of differential gene expression patterns between males and females. The evolution of such sex-biased expression patterns is constrained by pleiotropic functions of differentially expressed genes, such as widespread expression across tissues.

Methods: We investigated sex-biased gene expression and its relationship to tissue specificity in reproductive and somatic organs in the Northern pipefish, Syngnathus fuscus, a polygynandrous species with extreme paternal care and no evidence of sex chromosomes - conditions ripe for intra-locus sexual conflict.

Results: We found patterns of sex-biased expression in the gonads, liver, and gills of the Northern pipefish, with the largest number of sex-biased genes identified in the gonads. In general, sex-biased genes were only more tissue-specific in the reproductive tissues (gonads), but not in either of the somatic tissues (liver or gills). Sex-biased genes with evidence of branch-specific selection were also more tissue specific.

Discussion: We highlight the potential for different sex-specific selection pressures to be acting on each tissue type as there were widespread differences in the protein classes represented by sex-biased genes across both organs and sexes, although sex-biased genes did not experience stronger episodic selection than unbiased genes. Furthermore, our results support the hypothesis that broad expression can constrain the molecular evolution of a gene. The work presented here supports the potential for sex-biased gene expression to act as a mechanism for phenotypic differentiation between the sexes and increases our knowledge of patterns of gene expression in an unusual group of fishes.

Introduction: Sex-specific genotype and early organization can influence the expression of sexually dimorphic traits in vertebrates. We tested these hypotheses in male-typical behaviour and rapid change to bright colouration in the veiled chameleon (Chamaeleo calyptratus) with XX/XY sex chromosomes.

Methods: Hormonal manipulations included castration with and without testosterone replacement and testosterone administration in females.

Results: Long-term testosterone treatment induced male-typical sexual behaviour and an ability to switch to bright colouration in females, while castration suppressed these traits in males. These observations document that elevated testosterone alone is sufficient for the expression of these traits in both males and females. Surprisingly, high testosterone levels led to indiscriminate courtship behaviour, with frequent mating attempts directed at conspecifics regardless of their sex and testosterone level in both home cages and neutral arenas. This unexpected behaviour suggests that visual cues, such as body and head-casque size, may not reliably guide sex recognition during short distance encounters.

Conclusion: The dependence of the male-typical sexual behaviour and colour change on the elevated androgen levels contrast sharply with earlier results on skeletal traits (body size and head-casque size), which are fully developed in castrated males, demonstrating that the ontogeny of the sex-typical phenotype involves different mechanisms in the emerging model species of chameleons.

Introduction: The SOX9 gene encodes a transcription factor that acts downstream of the Y-linked SRY gene and plays a pivotal role in fetal testis development. Duplication of SOX9 or its regulatory sequences is a known cause of testicular or ovotesticular disorder of sex development (DSD) in chromosomal females (XX DSD). Numerous reports have described canine XX DSD, characterized by virilization (e.g., enlarged clitoris) and the presence of testes or ovotestes. This study aimed to identify SOX9 variants in a cohort of French Bulldogs with XX (SRY-negative) DSD.

Methods: In total, 27 DSD dogs were studied, including 19 with abdominal, spermatogenetically inactive testes; four with inactive testis and ovotestis; one with inactive testis and ovary; one with ovotestes; and in two dogs, histological analysis could not be performed. Moreover, 24 control females of the same breed, all with normal external female genitalia, were included.

Results: Three known DNA variants were identified in SOX9: a 3 bp insertion/deletion (CCT/---, rs852828782), a T>C SNP (rs22704771) in the 5' UTR, and an intronic T>G SNP (rs9183825). These variants were rare, and their distribution was similar in both cohorts. Additionally, the number of SOX9 gene copies was assessed using ddPCR. A single XX DSD case with additional skeletal malformations carried three copies of SOX9, while all other cases and control females had two copies.

Conclusion: We conclude that SOX9 duplication is a rare cause of XX DSD in French Bulldogs, and that the identified sequence variants in this gene are not associated with the disorder.

Introduction: Gonadal development and reproduction are under the control of the endocrine system, which acts along the brain-pituitary-gonad (BPG) axis. Besides well-known regulators of the BPG axis, such as the gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, the anti-Müllerian hormone (Amh) came into the focus of research on the BPG axis. Amh is expressed differently in the gonads of dominant and subordinate Nile tilapia (Oreochromis niloticus) males and could be involved in the regulation of the differently developed gonads. In addition, the regulatory networks and the control of gene expression depend on microRNAs (miRNAs), an often not considered epigenetic mechanism in hormonal research.

Methods: We used a long-term, stable social hierarchy of Nile tilapia males as an experimental system to identify differentially expressed (DE) miRNAs in the testes of dominant and subordinate animals. A Dual-Luciferase Reporter Assay and in vitro analysis of amh expression in primary testis cells were used to demonstrate predicted interactions.

Results: We identified 23 DE miRNAs in the testes of dominant and subordinate males and predicted the targets in the pools of DE genes. Using these data, we placed the identified GO terms and KEGG pathways in the context of differently developed gonads under social control. The most DE miRNA, oni-miR-499, is upregulated in the testes of dominants and regulates amh expression.

Conclusion: We conclude that oni-miR-499 affects testis development via amh expression in Nile tilapia. Many miRNAs and biological processes identified in our study could be conserved mechanisms of testis development.