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The illegal ivory trade remains a prime threat to elephant populations. Identification of ivory is crucial for combating illicit ivory trading. Studies have demonstrated that FTIR spectroscopy is one of the most suitable techniques for identifying ivory and its products. However, this technique could not have been fully utilized due to the lack of a reference IR spectral library/database. In light of this, the present study aimed to develop the FTIR spectral library for Asian elephant ivory. We collected eight Asian elephant ivory (n = 8) samples from our institute repository and recorded the FTIR spectrum. Further, based on the biochemical composition of ivory, we identified various characteristics, functional groups, and their respective wavenumbers. Furthermore, we used the FTIR spectrum of Asian elephant ivory as a reference to identify the fifteen carvings (n = 15) suspected to be of Asian elephant ivory. The results revealed that samples 1 -13 are visibly identical to the FTIR spectrum of Asian elephant ivory; in contrast, samples 14 and 15 do not match the FTIR spectrum of Asian elephant ivory. Hence, it is confirmed that out of fifteen samples, thirteen are likely to be of Asian elephant ivory origin. To confirm this finding, we employed the PLS-DA analysis. The result showed an R Square value of 0.9 for calibration and 0.75 for validation, and the model exhibited 100% accuracy in classifying the original and fake ivory samples. The results confirmed that FTIR combined with chemometrics analysis was useful for identifying ivory and fake materials. To validate the FTIR results, we extracted the DNA from suspected samples 1–15 and amplified elephant-specific D-loop and Sry (sex-determining region on the Y chromosome) genes. Subsequently, the PCR amplicons were examined on a 2.5% agarose gel and observed for samples 1–13, one band at 137 bp (for D-loop) and another at 97 bp (for Sry). These results indicated that samples 1–13 are of elephant origin, whereas samples 14 and 15 are not of elephant origin. To confirm this finding, the PCR amplicons (D-loop) from nine samples (1–9) were sequenced, and % similarity was analyzed. The results showed 96.6 to 100% similarity to the Mammuthus primigenius, Elephas maximus indicus, and Loxodonta africana. The primers (D-loop and Sry) used in this study are elephant-specific and do not distinguish the elephant species. Overall, DNA-based results supported the results from FTIR analysis and confirmed that the suspected samples 1–13 are of elephant origin and 14 and 15 are not of elephant origin. The current study has demonstrated the identification of ivory substitutes through FTIR spectral library for Asian elephant ivory, which is rapid, cost-effective, and has excellent potential for forensic analysis.Article Highlights: The FTIR spectral library was developed for Asian elephant ivory. The suspected elephant carvings were identified using the FTIR spectral library of Asian elephant ivory. The FTIR results were confirmed through PCR amplification of elephant-specific D-loop and Sry genes. [ABSTRACT FROM AUTHOR]

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer. [ABSTRACT FROM AUTHOR]

Abstract The illegal ivory trade remains a prime threat to elephant populations. Identification of ivory is crucial for combating illicit ivory trading. Studies have demonstrated that FTIR spectroscopy is one of the most suitable techniques for identifying ivory and its products. However, this technique could not have been fully utilized due to the lack of a reference IR spectral library/database. In light of this, the present study aimed to develop the FTIR spectral library for Asian elephant ivory. We collected eight Asian elephant ivory (n = 8) samples from our institute repository and recorded the FTIR spectrum. Further, based on the biochemical composition of ivory, we identified various characteristics, functional groups, and their respective wavenumbers. Furthermore, we used the FTIR spectrum of Asian elephant ivory as a reference to identify the fifteen carvings (n = 15) suspected to be of Asian elephant ivory. The results revealed that samples 1 -13 are visibly identical to the FTIR spectrum of Asian elephant ivory; in contrast, samples 14 and 15 do not match the FTIR spectrum of Asian elephant ivory. Hence, it is confirmed that out of fifteen samples, thirteen are likely to be of Asian elephant ivory origin. To confirm this finding, we employed the PLS-DA analysis. The result showed an R Square value of 0.9 for calibration and 0.75 for validation, and the model exhibited 100% accuracy in classifying the original and fake ivory samples. The results confirmed that FTIR combined with chemometrics analysis was useful for identifying ivory and fake materials. To validate the FTIR results, we extracted the DNA from suspected samples 1–15 and amplified elephant-specific D-loop and Sry (sex-determining region on the Y chromosome) genes. Subsequently, the PCR amplicons were examined on a 2.5% agarose gel and observed for samples 1–13, one band at 137 bp (for D-loop) and another at 97 bp (for Sry). These results indicated that samples 1–13 are of elephant origin, whereas samples 14 and 15 are not of elephant origin. To confirm this finding, the PCR amplicons (D-loop) from nine samples (1–9) were sequenced, and % similarity was analyzed. The results showed 96.6 to 100% similarity to the Mammuthus primigenius, Elephas maximus indicus, and Loxodonta africana. The primers (D-loop and Sry) used in this study are elephant-specific and do not distinguish the elephant species. Overall, DNA-based results supported the results from FTIR analysis and confirmed that the suspected samples 1–13 are of elephant origin and 14 and 15 are not of elephant origin. The current study has demonstrated the identification of ivory substitutes through FTIR spectral library for Asian elephant ivory, which is rapid, cost-effective, and has excellent potential for forensic analysis. Graphical abstract

Abstract Background Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism. Case presentation A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig’ cell tumour and a chronic endometritis in both uterine horns. Conclusions Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats.

Simple Summary: Phan Rang sheep is a term used to collectively refer to the sheep raised in the central Vietnam provinces of Ninh Thuan and Binh Thuan. Given the extreme weather conditions of their habitat, Phan Rang sheep are assumed to be heat-resilient. With climate change's mounting challenges, the sheep have become a focus of government-led breeding and conservation initiatives. However, there is a critical knowledge gap regarding the sheep's genetic information, including their origins, diversity, population structure, and genetics, as well as the morphological basis of their adaptive traits. This gap has hindered the development of breeding programs and genetic resource conservation efforts. In an effort to contribute to filling this knowledge gap, we employed a two-fold approach to investigate Phan Rang sheep's morphometrics and genetic lineages. First, we collected body conformational data to facilitate the quick identification of purebred individuals. Secondly, we collected and analyzed the mitochondrial DNA control region (D-loop) and the Y chromosome SRY and SRYM18 sequences to elucidate the maternal and paternal lineages of the sheep. Of the sheep analyzed for the D-loop, approximately one-third belonged to haplogroup A, while the remainder belonged to haplogroup B. For the paternal lineage, two main Y haplotypes, H5 and H6, were identified. Overall, the findings supported the hypothesis of dual origins for the Phan Rang sheep. The Phan Rang sheep, considered the sole indigenous breed of Vietnam, are primarily concentrated in the two central provinces of Ninh Thuan and Binh Thuan, with Ninh Thuan accounting for more than 90% of the country's sheep population. These provinces are known for their high temperatures and frequent droughts. The long-standing presence of the Phan Rang sheep in these regions suggests their potential resilience to heat stress—a trait of increasing interest in the face of global climate change. Despite the breed's significance, a critical knowledge gap hinders conservation and breeding programs. To address this, our study employed a two-pronged approach. First, we collected body conformational data to aid in breed identification. Second, we analyzed mitochondrial DNA (D-loop) and Y chromosome markers (SRY and SRYM18) to elucidate the maternal and paternal lineages. Among the 68 Phan Rang sheep analyzed for their D-loop, 19 belonged to mitochondrial haplogroup A, while 49 belonged to haplogroup B. The haplogroups can be subdivided into 16 unique haplotypes. All 19 rams surveyed for their paternal lineages belonged to haplotypes H5 and H6. These findings strongly support the hypothesis of dual origins for the Phan Rang sheep. This study presents the first genetic data for the Phan Rang breed, providing crucial insights for future research and conservation efforts. [ABSTRACT FROM AUTHOR]

Background: Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism. Case presentation: A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig' cell tumour and a chronic endometritis in both uterine horns. Conclusions: Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats. [ABSTRACT FROM AUTHOR]

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Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer.

This study aimed to determine the kinship and genetic diversity between Limousin and Madrasin cattle based on the sex determining region-Y (SRY) gene. SRY gene is used in the analysis of genetic diversity for sex determination based on the paternal pathway (Y chromosome). The DNA samples used for this study were 10 frozen straw of Limousin cattle and 10 samples of Madrasin cattle. The method used in this research was a descriptive analysis by duplex polymerase chain reaction and analyzing the results of the SRY gene sequencing of limousine cattle and Madrasin cattle. In the present study, we showed that the SRY gene of Madrasin cattle and Limousine cattle could be amplified with SRY F and SRY R primers with a PCR product length of 318 bp. Based on these results, Madura, Limousin, and Madrasin cattle had similarities based on the SRY gene (paternal pathway). [ABSTRACT FROM AUTHOR]

The reproductive efficiency improvements that can be achieved in bovine herds highly depend on the male, as the bulls account for approximately 80% of the gene pool. Likewise, age can impact the sires' reproductive efficiency through its seminal quality, which is strongly influenced by the bull's sexual maturity. The study aimed to assess the bull's age effect on the X and Y chromosomes-bearing spermatozoa ratio in semen. Sixteen Brahman bulls (Bos indicus) were grouped into two age range and their reproductive capacity was assessed. Genomic DNA was extracted from a single collection of semen to quantify by qPCR (quantitative polymerase chain reaction) the PLP and SRY genes, used as sexual chromosome markers, and autosomal GAPDH as the reference gene. The values obtained were compared using the delta Ct (2-Ct) method and validated with the use of a commercial sample of semen sexed for the X chromosome. The SRY gene had a proportion of 43% in bulls of 4-5 years of age and 32% in the group of 9-10 years, while the proportions of the PLP gene were 57% in bulls of 4-5 years and 68% in the 9-10 years group. This deviation from the expected ratio (1:1) in bulls of nine and ten years old with a preponderance of the X chromosome content might suggest a possible influence of age in the sex chromosome proportions in the spermatozoa; however, these results were not statistically significant. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer and the fifth cause of cancer-related deaths worldwide with a poor 5-year survival. SOX family genes play a role in the processes involved in cancer development such as epithelial–mesenchymal transition (EMT), the maintenance of cancer stem cells (CSCs) and the regulation of drug resistance. We analyzed the expression of SOX2-OT, SOX6, SOX8, SOX21, SOX30 and SRY genes in HNSCC patients using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, to assess their biological role and their potential utility as biomarkers. We demonstrated statistically significant differences in expression between normal and primary tumor tissues for SOX6, SOX8, SOX21 and SOX30 genes and pointed to SOX6 as the one that met the independent diagnostic markers criteria. SOX21 or SRY alone, or the panel of six SRY-related genes, could be used to estimate patient survival. SRY-related genes are positively correlated with immunological processes, as well as with keratinization and formation of the cornified envelope, and negatively correlated with DNA repair and response to stress. Moreover, except SRY, all analyzed genes were associated with a different tumor composition and immunological profiles. Based on validation results, the expression of SOX30 is higher in HPV(+) patients and is associated with patients’ survival. SRY-related transcription factors have vast importance in HNSCC biology. SOX30 seems to be a potential biomarker of HPV infection and could be used as a prognostic marker, but further research is required to fully understand the role of SOX family genes in HNSCC.

The Phan Rang sheep, considered the sole indigenous breed of Vietnam, are primarily concentrated in the two central provinces of Ninh Thuan and Binh Thuan, with Ninh Thuan accounting for more than 90% of the country’s sheep population. These provinces are known for their high temperatures and frequent droughts. The long-standing presence of the Phan Rang sheep in these regions suggests their potential resilience to heat stress—a trait of increasing interest in the face of global climate change. Despite the breed’s significance, a critical knowledge gap hinders conservation and breeding programs. To address this, our study employed a two-pronged approach. First, we collected body conformational data to aid in breed identification. Second, we analyzed mitochondrial DNA (D-loop) and Y chromosome markers (SRY and SRYM18) to elucidate the maternal and paternal lineages. Among the 68 Phan Rang sheep analyzed for their D-loop, 19 belonged to mitochondrial haplogroup A, while 49 belonged to haplogroup B. The haplogroups can be subdivided into 16 unique haplotypes. All 19 rams surveyed for their paternal lineages belonged to haplotypes H5 and H6. These findings strongly support the hypothesis of dual origins for the Phan Rang sheep. This study presents the first genetic data for the Phan Rang breed, providing crucial insights for future research and conservation efforts.

In forensic odontology, Amelogenin and Sex-Determining Region on Y chromosome genes are commonly used for sex identification. Nevertheless, the amplification of both of these genes encounters limitations in determining sex, primarily due to deletions observed in certain racial groups and the influence of genetic disorders on these genes. This research aims to assess the precision of simultaneously amplifying both genes using multiplex polymerase chain reaction on samples derived from teeth that have been subjected to various forensic conditions. In this study, a total of 70 teeth, comprising 35 males and 35 females, were utilized, and all samples underwent genetic analysis to determine sex following exposure to different forensic scenarios. The findings revealed that both the quantity and quality of genetic material were reduced when exposed to harsh environmental conditions. Notably, the amplification of the sex-determining region on the Y chromosome gene outperformed the amplification of Amelogenin and achieved a sex-determination accuracy rate of 100%. In conclusion, dental pulp serves as a valuable source of genetic material even after exposure to diverse environmental conditions, and it can effectively be used for sex estimation purposes.

46, XX male syndrome is a rare disorder of sex development, which usually has a 46, XX chromosome karyotype and positive sex-determining region Y gene (SRY), normal external genitalia and male phenotype. Most of them come to hospital due to adult infertility. The patients with SRY negative 46, XX male syndrome are often accompanied by external genital malformations, and most of them seek the treatment because of abnormal sexual development at young age. A case of SRY negative 46, XX male syndrome was reported in this paper. The development of external genitalia and secondary sexual characteristics in this patient were normal male type. The chromosome karyotype was 46, XX, while SRY was negative and AZF region was deleted. The hypergonadotropin hypogonadism and azoospermia were diagnosed. As for the fertility requirement of this patient, artificial insemination by donor was recommended. [ABSTRACT FROM AUTHOR]

Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) with mild external genital abnormalities may be diagnosed after puberty. Here, we report a case of 46,XY complete gonadal dysgenesis with a novel missense variant in sex-determining region Y (SRY), diagnosed after primary amenorrhea. A 15-yr-old patient presented to our gynecology department with a chief complaint of amenorrhea. The patient was diagnosed with a 46,XY karyotype, and SRY gene positivity. Gonadotropin levels were high, whereas testosterone levels were low. A pelvic magnetic resonance imaging (MRI) revealed a hypoplastic uterus; however, no gonads could be identified. Laparoscopy revealed bilateral streak gonads, fallopian tube-like structures, and the uterus. The gonads were removed based on the risk of gonadal malignancy. Comprehensive genetic analysis of DSD revealed a previously unreported SRY variant, c.271A>T, p.Ser91Cys, and in silico analysis predicted the variant to be pathogenic. The patient was diagnosed with 46,XY complete gonadal dysgenesis with a novel missense variant in SRY. The patient continued female hormone replacement therapy and experienced breast enlargement and cyclic menstruation. Determining the etiology of DSD can be difficult, causing anxiety in patients and their families. In addition to surgical scrutiny, genetic analysis is important to aid in diagnosis and reassure patients and their families. [ABSTRACT FROM AUTHOR]

We report a case of a fetus with 46,XX testicular disorder of sex development detected prenatally. This fetus was found abnormally due to non‐invasive prenatal testing. Amniocentesis revealed SRY gene on the X chromosome of the fetus. The related literature was reviewed, and the advantages and limitations of various prenatal diagnostic techniques were discussed. The combination of non‐invasive prenatal testing and various prenatal diagnostic techniques has enabled more fetuses with sex reversal to be detected. [ABSTRACT FROM AUTHOR]

The presence of intersexuality in goat breeds is one of the most popular, and challenging issues. Therefore, understanding the genetic complexity of this phenomenon at the DNA level may help to discover the molecular mechanisms of sexual differentiation in this species. A solution to this problem is proposed in the development of a DNA test using sex-determination candidate genes. With this motivation, the main goal of the present report was to identify the pseudohermaphrodite polled goats based on ZFX and SRY sexdetermination candidate gene findings. Overall, data were collected from 11 individuals (4 females, 4 males, and 3 anatomically female goats (intersex) were chosen for PCR analysis using ZFX and SRY specific primers sequence. For this reason, genomic DNA extraction and PCR amplification were done according to routinely available laboratory protocol. Two ZFX and SRY-specific primer sets were applied for PCR amplification. Interestingly, our results were re-confirmed, and PCR products were amplified by ZFX primer yielding a band of 445 bp in both female and intersex goats. Furthermore, SRY expressed 169 bp in both male and intersex goats. In summary, these results suggest that SRY candidate gene may provide insight into the factors affecting the intersexuality issue in goat breeds. [ABSTRACT FROM AUTHOR]

The process of sex determination (SD) and sex differentiation (Sd) with associated sex-specific behaviour in teleosts is brought about by genetic factors and environmental factors under the influence of chemical messengers. SD is initiated by inherited genes, which in turn influence Sd by the production of hormones. To understand the plasticity of SD in fishes, the functional role of genes must be clearly elucidated. During early development, the dimorphic expression of male and female are mediated by the differentially sexualized brain. In mammals, SD region (SDR) on the Y chromosome (SRY) can be considered as male-specific copy of SOX3 and in the absence of SRY in teleosts suggests SD might be regulated by alternate genes. DM (doublesex/mab)-related genes, AMH (anti-mullerian hormone), TGF-b (transforming growth factor beta), GSDF (gonadal soma derived growth factor) and other genes (around 18) located in chromosomes of teleosts are found to be responsible for SD. The SD gene, sdY (sexually dimorphic on the Y chromosome) has been detected in more than 15 salmonid species, and in medaka and tilapia SD system is governed by heterogametic mechanism. In mullet, Mugil cephalus Dor et al. identified 27 SDR genes and suggested to be potential candidate genes for SD. Recently whole-genome sequencing data were produced from mullet and assembled into a draft genome sequence in which >30 loci are potentially associated with SD. Further analysis is required to know the involvement of each sex-biased gene for its functional influence on sex. Investigators attempted to know the sex-linkage group in tilapia and found that 2 linkage group i.e. LG1 and LG22 show SD loci, whereas in mullet it was documented that LG8 is the SD loci. Rigorous study with all male population(YY) or knockout of male marker gene, might give conclusive understanding on SD in future. The review highlights the absence of genomic understanding of SD and SDR genes for futuristic direction of research.

Polygenic sex determination (PSD) is defined as the determination of sexual phenotype by the combined action of two or more genes at independently inherited loci in one individual. PSD should not be ascribed to multiple alleles at the same sex determination (SD) locus that may be polymorphic in the population, elements of a common biochemical pathway, and to multiple sex chromosomes that are polymorphic in a population, or neo-sex chromosomes or sex chromosome chains when sexual development of the individuum is triggered by one SD locus. A consistent nomenclature that adheres to accepted definitions of genes and alleles is recommended. Evolutionary theory predicts that PSD is an unstable state. Documented cases of PSD are rare. Those examined are best explained by transitionary stages during sex chromosome turnover or aberrant situations in hybrids between species with different sex chromosomes. Genetic sex determination (SD) in most vertebrates is controlled by a single master sex gene, which ensures a 1:1 sex ratio. However, more complex systems abound, and several have been ascribed to polygenic SD (PSD), in which many genes at different loci interact to produce the sexual phenotype. Here we examine claims for PSD in vertebrates, finding that most constitute transient states during sex chromosome turnover, or aberrant systems in species hybrids. To avoid confusion about terminology, we propose a consistent nomenclature for genetic SD systems. [ABSTRACT FROM AUTHOR]

Mechanisms that regulate sexual chromosome distribution in the canine ejaculate are not quite understood with no data about both its variation over time and the effect on reproductive parameters. With the aim to deepen these aspects, ten purebred male dogs, aged between 1.5 and 8.5 years, underwent digito-digital semen collection every three months throughout one year. A quantitative real-time PCR method was used to measure the sperm-sex ratio. The sperm-sex ratio was slightly female-biased without a significant difference throughout the year, albeit with some individual dynamic fluctuation over time. The total number of spermatozoa (P < 0.05) but not serum testosterone concentration nor the age of the dog was related to the sperm-sex ratio. In particular, dogs with a lower spermatozoa rate showed a greater number of spermatozoa in the ejaculate than dogs with a higher rate. A decreasing trend of X spermatozoa rate was also observed in dogs younger than 5 years of age. Quantitative real-time PCR proved to be an accurate, practical, and reliable method for determining the sperm-sex ratio in dogs. Further studies on a large scale could help to deepen the factors involved in the sperm-sex ratio and consequently in the offspring-sex ratio, opening new frontiers in canine andrology. [ABSTRACT FROM AUTHOR]

The expression of sex determining region of the Y chromosome (Sry) in the fetal gonads is important for male development. In a mouse model of disorders of sex development (C57BL/6 (B6)- XYPOS), the gonadal phenotype and the timing of Sry expression differ due to differences among B6 substrains as the genetic background. Since differences in Sry expression among B6 substrains have been speculated, the present study examined Sry expression in B6J, B6JJmsSlc, and B6NCrl mice. These substrains differed in the number of Sry-expressing cells in the gonads of embryonic mice at each developmental stage, with B6NCrl having more than the other strains. The substrains differed also in the number of Sry-expressing cells between the left and right gonads, with B6J and B6NCrl, but not B6JJmsSlc, showing left gonad-dominant Sry expression. Substrain differences existed also in the distribution of Sry-expressing cells in the medial and lateral directions of gonads. In addition, in the left gonad-dominant Sry-expressing substrains B6J and B6NCrl, the medial and central regions of the left gonad had more Sry-expressing cells than those of the right gonad. Substrains of B6 mice have not always been considered in sex differentiation studies. In the present study, however, we observed substrain differences in the number of Sry-expressing cells, left-right distribution, and medial/lateral distribution during the early stages of gonadal development in B6 mice. Therefore, future studies on sex differentiation in B6 mice should consider substrain differences. [ABSTRACT FROM AUTHOR]

During mammalian development, gonadal sex determination results from the commitment of bipotential supporting cells to Sertoli or granulosa cell fates. Typically, this decision is coordinated across the gonad to ensure commitment to a single organ fate. When unified commitment fails in an XY mouse, an ovotestis forms in which supporting cells in the center of the gonad typically develop as Sertoli cells, while supporting cells in the poles develop as granulosa cells. This central bias for Sertoli cell fate was thought to result from the initial expression of the drivers of Sertoli cell fate, SRY and/or SOX9, in the central domain, followed by paracrine expansion to the poles. However, we show here that the earliest cells expressing SRY and SOX9 are widely distributed across the gonad. In addition, Sertoli cell fate does not spread among supporting cells through paracrine relay. Instead, we uncover a center-biased pattern of supporting cell precursor ingression that occurs in both sexes and results in increased supporting cell density in the central domain. Our findings prompt a new model of gonad patterning in which a density-dependent organizing principle dominates Sertoli cell fate stabilization. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the most common movement disorder and is caused by the loss of dopaminergic neurons in the substantia nigra. The first motor symptoms of PD begin to appear when more than 60% of dopaminergic neurons are already lost. Although the etiology of PD is not fully understood, PD is believed to result from the complex interactions between genetic and environmental factors. Previous studies demonstrated that men are at least 1.5 times more likely to develop PD than women. The current kulstudy aimed to investigate whether SRY, a chromosome gene, plays a role in the pathogenesis of PD using in silico methods. Material and Method The mRNA expression of SRY in different human tissues was analyzed using the Human Protein Atlas (HPA). The interactions between SRY and PD-related genes were analyzed using the STRING and GeneMANIA databases. The JASPAR database was used to determine the putative binding sites of SRY in the promoter regions of some PD-related genes. Finally, the BioGRID and GeneMANIA databases were used to identify the key genes that interact with SRY. Results In silico analyses revealed that there are SRY binding sites in the promoter regions of some PD-associated genes and that SRY can regulate androgen receptor (AR) signaling. Conclusion These findings suggest that SRY may play a role in the pathogenesis of PD and may thus serve as a molecular target for developing new therapeutic strategies against PD. [ABSTRACT FROM AUTHOR]

The aim of this study was sex-detection of nexborn rabbits with molecular-genetics analyses of SRY (specific region of Y chromosome) sequence. This region is present only in male animals, in females is missing. We analysed 16 newborn rabbits (native in two litters of females lines P91 and M91) by using polymerase chain reaction with specific primers. PCR product was visualised at 3% agarose gel. SRY – PCR fragment (242 bp) was detected in 8 animals, 8 animals had no fragment present. All young were evaluated according to outer genitals at 3 weeks of age. This technology provides partly selective tool for categorization of the females and males in further reproductive process. Both sexes of newborn rabbits can be used for control of production of special enzymes under genetic control of the gonosomes and also in human medicine for aplication of xenoimplatates

Abstract Background Permanent progression of paternal age and development of reproductive medicine lead to increase in number of children conceived with assisted reproductive techniques (ART). Although it is uncertain if ARTs have direct influence on offspring health, advanced paternal age, associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT), more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development, majority of which are associated with the SRY gene. Case presentation We report a case of a non-invasive prenatal testing and ultrasound sex discordance in a 46,XY karyotype female fetus with an SRY pathogenic variant, who was conceived through an intracytoplasmic sperm injection (ICSI) due to severe oligozoospermia of the father. Advanced mean age of ICSI patients is associated with risk of de novo mutations and monogenic disorders in the offspring. Additionally, ICSI patients have higher risk to harbour infertility-predisposing mutations, including mutations in the SRY gene. These familial and de novo genetic factors predispose ICSI-conceived children to congenital malformations and might negatively affect reproductive health of ICSI-patients’ offspring. Conclusions Oligozoospermic patients planning assisted reproduction are warranted to undergo genetic counselling and testing for possible inherited and mosaic mutations, and risk factors for de novo mutations.

Simple Summary: Freemartinism is the most common type of disorder of sex development (DSD) in heifers; it is caused by the formation of placental anastomoses between heterosexual twin fetuses and the transfer of masculine factors produced by the testes of the male co-twin to the female fetus. The abnormal development of external genitalia is commonly observed in such heifers, but it cannot be assumed that each heifer with ambiguous genitalia is an example of freemartinism. We genetically analyzed five DSD heifers, and four appeared to be freemartins, as revealed by the presence of XX/XY leukocyte chimerism. The fifth heifer had a normal XX sex chromosome complement and lacked the Y-chromosome-derived genes (SRY, ZFY and AMELY) in blood cells. This heifer was extensively studied through genetic, anatomical, and histological approaches. Postmortem anatomical and histological analysis showed the presence of normal ovaries, oviducts, and uterus, while three Y-linked genes (SRY, ZFY, and AMELY) were detected in DNA isolated from these organs. In conclusion, we suggest that among virilized heifers, there are, besides freemartins with XX/XY leukocyte chimerism, also cases with XX/XY chimerism in internal genitalia, the etiology of which remains unknown. Five DSD heifers underwent genetic analysis in the present study. We cytogenetically analyzed in vitro cultured leukocytes and searched for SRY, AMELX/AMELY and ZFX/ZFY genes in leukocytes and hair follicles, finding that four of the studied heifers were freemartins (XX/XY leukocyte chimerism). The fifth case had an underdeveloped vulva localized ventrally and cranially to the mammary gland, a normal female sex chromosome complement (60,XX) in the leukocytes, and a lack of Y-chromosome-derived genes in the leukocytes and hair follicles. Postmortem anatomical examination of this heifer revealed the presence of normal ovaries with follicles, uterus, and oviducts, but molecular detection of the SRY, ZFX, ZFY,AMELX, and AMELY genes in these organs indicated the presence of a cell line carrying the Y chromosome. Further analysis of twelve microsatellite markers revealed the presence of additional variants at six loci in DNA samples derived from the reproductive organs; XX/XY chimerism was thus suspected in these samples. On the basis of the detection of AMELY (Y-linked) versus AMELX (X-linked) and SOX9 (autosomal) versus AMELY genes by droplet digital PCR (ddPCR), the Y/X and Y/autosome ratios were evaluated; they indicated the presence of XX and XY cell lines in the reproductive tissues. Our study showed that XX/XY chimerism can be present in the internal reproductive organs of the virilized heifers with a normal female set of sex chromosomes (60,XX) and a lack of Y-chromosome-derived genes in the leukocytes. The etiology of this phenomenon remains unknown. [ABSTRACT FROM AUTHOR]

The elucidation of molecular genetic mechanisms in the development of rare inherited diseases is crucial in understanding the processes of pathogenesis, improving the diagnosis and treatment of patients. The aim of our study was to determine the nature of genetic defects in a patient who showed signs of dysfunction of sexual development in combination with neuromuscular pathology. The study included: clinical and genealogical examination, ultrasonographic examination, electroneuromyography, study of biochemical parameters in serum: hormones and enzymes, molecular cytogenetic study using the FISH method, whole exome sequencing of the patient's DNA analysis, bioinformatiсal analysis. The patient showed signs of primary (hypergonadotropic) hypogonadism and polyneuropathic changes in the lower extremities (axonal-demyelinating). It was found that these clinical characteristics of the patient's phenotype do not agree with any description of the clinical phenotype registered in the OMIM International Database. According to the results of molecular cytogenetic study in the patient's karyotype, an unbalanced translocation of the Yp11.3 region containing the SRY gene to the short arm region of the X chromosome Xp22.33 with the formation of a derivative chromosome X was detected. On another side, the results of whole exome sequencing of the patient's genomic DNA revealed the presence of a homozygous mutation chr5: 131165096 C>G (c.110 G>C, p.Arg37Pro) in the HINT1 gene. Thus, it can be concluded that the phenotype with signs of disorders of sex differentiation in combination with axonal neuropathy with myotonia is due to two independent pathogenetic factors - unbalanced translocation of the SRY gene sequence on the chromosome X during paternal spermatogenesis and inheritance of the HINT1 gene homozygous missense mutation (c.110 G>C, p.Arg37Pro). These results support the effectiveness of a combination of molecular cytogenetic research methods and the results of high-performance WES to elucidate the molecular mechanisms of pathogenesis in patients with rare clinical phenotypes. [ABSTRACT FROM AUTHOR]

The process of sex determination (SD) and sex differentiation (Sd) with associated sex-specific behaviour in teleosts is brought about by genetic factors and environmental factors under the influence of chemical messengers. SD is initiated by inherited genes, which in turn influence Sd by the production of hormones. To understand the plasticity of SD in fishes, the functional role of genes must be clearly elucidated. During early development, the dimorphic expression of male and female are mediated by the differentially sexualized brain. In mammals, SD region (SDR) on the Y chromosome (SRY) can be considered as male-specific copy of SOX3 and in the absence of SRY in teleosts suggests SD might be regulated by alternate genes. DM (doublesex/mab)-related genes, AMH (anti-mullerian hormone), TGF-b (transforming growth factor beta), GSDF (gonadal soma derived growth factor) and other genes (around 18) located in chromosomes of teleosts are found to be responsible for SD. The SD gene, sdY (sexually dimorphic on the Y chromosome) has been detected in more than 15 salmonid species, and in medaka and tilapia SD system is governed by heterogametic mechanism. In mullet, Mugil cephalus Dor et al. identified 27 SDR genes and suggested to be potential candidate genes for SD. Recently whole-genome sequencing data were produced from mullet and assembled into a draft genome sequence in which >30 loci are potentially associated with SD. Further analysis is required to know the involvement of each sex-biased gene for its functional influence on sex. Investigators attempted to know the sex-linkage group in tilapia and found that 2 linkage group i.e. LG1 and LG22 show SD loci, whereas in mullet it was documented that LG8 is the SD loci. Rigorous study with all male population(YY) or knockout of male marker gene, might give conclusive understanding on SD in future. The review highlights the absence of genomic understanding of SD and SDR genes for futuristic direction of research. [ABSTRACT FROM AUTHOR]

SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms. The discovery of the master sex-determining gene SRY in 1990 was pivotal for the understanding of how testis development is initiated in mammals. With this discovery, an entire family of SOX factors were uncovered that play crucial roles in cell fate decisions during development. The importance of SOX genes in human reproductive development is evident from the various disorders of sex development (DSD) upon loss or overexpression of SOX gene function. Here, we review the roles that SOX genes play in gonad development and their involvement in DSD. We start with an overview of sex determination and differentiation, DSDs, and the SOX gene family and function. We then provide detailed information and discussion on SOX genes that have been implicated in DSDs, both at the gene and regulatory level. These include SRY, SOX9, SOX3, SOX8, and SOX10. This review provides insights on the crucial balance of SOX gene expression levels needed for gonad development and maintenance and how changes in these levels can lead to DSDs. [ABSTRACT FROM AUTHOR]

SRY is the Y‐chromosomal gene that determines male sex development in humans and most other mammals. After three decades of study, we still lack a detailed understanding of which domains of the SRY protein are required to engage the pathway of gene activity leading to testis development. Some insight has been gained from the study of genetic variations underlying differences/disorders of sex determination (DSD), but the lack of a system of experimentally generating SRY mutations and studying their consequences in vivo has limited progress in the field. To address this issue, we generated a mouse model carrying a human SRY transgene able to drive testis determination in XX mice. Using CRISPR‐Cas9 gene editing, we generated novel genetic modifications in each of SRY's three domains (N‐terminal, HMG box, and C‐terminal) and performed a detailed analysis of their molecular and cellular effects on embryonic testis development. Our results provide new functional insights unique to human SRY and present a versatile and powerful system in which to functionally analyze variations of SRY including known and novel pathogenic variants found in DSD. [ABSTRACT FROM AUTHOR]

Abstract Background We analyzed a combined segment (2032-bp) of the sex-determining region and the testis-specific protein of the Y-chromosome (Y-DNA) gene to clarify the gene flow and phylogenetic relationships of the long-tailed macaques (Macaca fascicularis) in Southeast Asia. Phylogenetic relationships were constructed using the maximum likelihood, Bayesian inference, and the median-joining network from a total of 164 adult male M. fascicularis from 62 localities in Malaysia, including sequences from the other regions from previous studies. Results Based on Y-DNA, we confirm the presence of two lineages of M. fascicularis: the Indochinese and Sundaic lineages. The Indochinese lineage is represented by M. fascicularis located northwards of the Surat Thani-Krabi depression region and is introgressed by the Macaca mulatta Y-DNA. The Sundaic lineage is free from such hybridization event, thus defined as the original carrier of the M. fascicularis Y-DNA. We further revealed that the Sundaic lineage differentiated into two forms: the insular and the continental forms. The insular form, which represents the ancestral form of M. fascicularis, consists of two haplotypes: a single homogenous haplotype occupying the island of Borneo, Philippines, and southern Sumatra; and the Javan haplotype. The more diverse continental form consists of 17 haplotypes in which a dominant haplotype was shared by individuals from southern Thai Peninsular (south of Surat Thani-Krabi depression), Peninsular Malaysia, and Sumatra. Uniquely, Sumatra contains both the continental and insular Y-DNA which can be explained by a secondary contact hypothesis. Conclusions Overall, the findings in this study are important: (1) to help authority particularly in Malaysia on the population management activities including translocation and culling of conflict M. fascicularis, (2) to identify the unknown origin of captive M. fascicularis used in biomedical research, and; (3) the separation between the continental and insular forms warrants for the treatment as separate management units.

Background: Permanent progression of paternal age and development of reproductive medicine lead to increase in number of children conceived with assisted reproductive techniques (ART). Although it is uncertain if ARTs have direct influence on offspring health, advanced paternal age, associated comorbidities and reduced fertility possess significant risks of genetic disorders to the offspring. With a broad implementation of a non-invasive prenatal testing (NIPT), more cases of genetic disorders, including sex discordance are revealed. Among biological causes of sex discordance are disorders of sexual development, majority of which are associated with the SRY gene.Case Presentation: We report a case of a non-invasive prenatal testing and ultrasound sex discordance in a 46,XY karyotype female fetus with an SRY pathogenic variant, who was conceived through an intracytoplasmic sperm injection (ICSI) due to severe oligozoospermia of the father. Advanced mean age of ICSI patients is associated with risk of de novo mutations and monogenic disorders in the offspring. Additionally, ICSI patients have higher risk to harbour infertility-predisposing mutations, including mutations in the SRY gene. These familial and de novo genetic factors predispose ICSI-conceived children to congenital malformations and might negatively affect reproductive health of ICSI-patients' offspring.Conclusions: Oligozoospermic patients planning assisted reproduction are warranted to undergo genetic counselling and testing for possible inherited and mosaic mutations, and risk factors for de novo mutations. [ABSTRACT FROM AUTHOR]

The sex-determining region of the Y chromosome, Sry/SRY, is an initiation factor for testis development in both humans and mice. Although the functional compatibility between murine SRY and human SRY was previously examined in transgenic mice, their equivalency remains inconclusive. Because molecular interaction and timeline of mammalian sex determination were mostly described in murine experiments, we generated a mouse model in which Sry was substituted with human SRY to verify the compatibility. The mouse model had the human SRY open reading frame at the locus of murine Sry exon 1— Sry (SRY) mice—and was generated using the CRISPR/Cas9 system. The reproductive system of the mice was analyzed. The expression of human SRY in the fetal gonadal ridge of Sry (SRY) mice was detected. The external and internal genitalia of adult Sry (SRY) mice were similar to those of wild-type females, without any significant difference in anogenital distance. Sry (SRY) mice obtained gonads, which were morphologically considered as ovaries. Histological analysis revealed that the cortical regions of gonads from adult Sry (SRY) mice contained few follicles. We successfully replaced genes on the Y chromosome with targeted genome editing using the CRISPR/Cas9 system. Because the Sry (SRY) XY mice did not develop testis, we concluded that human SRY was insufficient to drive testis development in mouse embryos. The difference in response elements and lack of glutamine-rich domains may have invalidated human SRY function in mice. Signal transduction between Sry / SRY expression and Sox9 / SOX9 activation is possibly organized in a species-specific manner. [ABSTRACT FROM AUTHOR]

Abstract Background Sex determination can be useful in forensic casework, such as in mass disasters, transportation accidents, and cases of a missing person or sexual assault. The remnants of the body can be traced by DNA of the victim, using samples from various sources such as teeth, oral epithelial tissue, and saliva. Main body The review aimed to describe research in forensic dentistry with DNA source from the oral region and methods of the applied DNA analysis. A search in PubMed, Google Scholar, and Scopus electronic databases from 2009 to 2019 was conducted to include studies according to PRISMA guidelines. Ten studies were eligible for the review. Genetic markers originated from dentin, dental pulp, saliva, or epithelial cells from buccal tissue and prosthesis. The applied DNA analysis methods were PCR, real-time PCR, and nested PCR. Conclusions The published articles mostly showed successful DNA extraction and sex determination, but the rate of success declined as the sample source underwent manipulation to mimic the forensic conditions. Amelogenin, SRY, and DYS14 were reliable indicators for sex determination. Molecular analysis has proved to be efficient and accurate, but the daily forensic practice must select the most appropriate method according to the available body remnants.

Abstract Background The commonly used laboratory rat, Rattus norvegicus, is unique in having multiple Sry gene copies found on the Y chromosome, with different copies encoding amino acid variations that influence the resulting protein function. It is not clear which Sry genes are expressed at the onset of testis differentiation or how their expression correlates with that of other genes in testis-determination pathways. Methods Here, two independent E11–E14 developmental RNAseq datasets show that multiple Sry genes are expressed at E12–E13. Results The identified copies expressed during testis initiation include Sry4A, Sry1, and Sry3C, which are conserved in every strain of Rattus norvegicus with genomes sequenced to date. Conclusions This work represents a first step in defining the complex environment of rat testis differentiation that can open the door for generating sex reversal model systems using embryo manipulation techniques that have been available in the mouse but not the rat.

Rhodioloside has been shown to protect cells from hypoxia injury, and bone marrow mesenchymal stem cells have a good effect on tissue repair. To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury, a rat model of spinal cord injury was established using the Infinite Horizons method. After establishing the model, the rats were randomly divided into five groups. Rats in the control group were intragastrically injected with phosphate buffered saline (PBS) (5 μL). PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm. Rats in the rhodioloside group were intragastrically injected with rhodioloside (5 g/kg) and intramuscularly injected with PBS. Rats in the mesenchymal stem cell (MSC) group were intramuscularly injected with PBS and intramuscularly with MSCs (8 × 106/mL in a 50-μL cell suspension). Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs. Rats in the rhodioloside + Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside. One week after treatment, exercise recovery was evaluated with a modified combined behavioral score scale. Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue. Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord. Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord. The results showed that: (1) compared with the other groups, the rhodioloside + Ad-HIF-MSC group exhibited the highest combined behavioral score (P < 0.05), the most recovered tissue, and the greatest number of neurons, as indicated by Pischingert’s methylene blue staining. (2) Compared with the PBS group, HIF-1 protein expression was greater in the rhodioloside group (P < 0.05). (3) Compared with the Ad-HIF-MSC group, Sry mRNA levels were higher in the rhodioloside + Ad-HIF-MSC group (P < 0.05). These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue. This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine, China (approval No. 2015KYLL029) in June 2015.

Consanguineous marriages cause rare blended phenotypes in common geographies and the emergence of different homozygous diseases in the same family. In this article, a family in which different rare mechanisms come together as a result of consanguineous marriage is presented. A 2-yearold proband with a blended phenotype with sex development disorder and coenzyme Q10 deficiency has psychomotor retardation, micropenis, undescended testicles, dysmorphic findings, hypotonia, and the gonads have a bilateral testicular appearance and are located in the inguinal canal. In the patient's brother, who previously died due to hydrocephalus, a non-sense homozygous variant c.1051C>T p.(Arg351*) was detected in the 7th exon of the NM_001134830 transcript of the AHI1 gene. The patient's cytogenetic analysis result is: 46,XX,ish,der(X)t(X;Y)(p22.3;p11.2)(SRY+). In the molecular karyotyping analysis performed due to hypotonia, psychomotor retardation and dysmorphic findings; a change of 2.1 Mb in size was detected in the Xp22.33p22.32 region and 3.1 Mb in size in the Yp11.2 region. This change is 46,XX sex reversal 1; it has been associated with SRXX1 (OMIM number:#400045) disease. In the subsequent whole exome analysis, a c.437T>G (Phe146Cys) missense homozygous probable pathogenic variant was detected in the NM_016035 transcript in the 5th exon of the COQ4 gene, which explains other clinical findings. In primary deficiency of coenzyme Q10 (OMIM number: #616276), which is a lipid component of the mitochondrial respiratory chain, symptoms vary; hypotonia, decreased coQ levels in muscle tissue, regression in psychomotor development, seizures, and increased serum lactate levels are observed. It is generally lethal in the first years of life, and in this respect, it is thought that the clinical findings of the proband will contribute to the literature with their milder course. To our knowledge, there is no other case in the literature reporting a sexual development anomaly or primary CoQ10 deficiency. [ABSTRACT FROM AUTHOR]

In vertebrates, gonadal sex determination is the process by which transcription factors drive the choice between the testicular and ovarian identity of undifferentiated somatic progenitors through activation of 2 different transcriptional programs. Studies in animal models suggest that sex determination always involves sex-specific transcription factors that activate or repress sex-specific genes. These transcription factors control their target genes by recognizing their regulatory elements in the non-coding genome and their binding motifs within their DNA sequence. In the last 20 years, the development of genomic approaches that allow identifying all the genomic targets of a transcription factor in eukaryotic cells gave the opportunity to globally understand the function of the nuclear proteins that control complex genetic programs. Here, the major transcription factors involved in male and female vertebrate sex determination and the genomic profiling data of mouse gonads that contributed to deciphering their transcriptional regulation role will be reviewed. [ABSTRACT FROM AUTHOR]

Mammalian male sex differentiation is triggered during embryogenesis by the activation of the Y-linked testis-determining gene SRY. Since insufficient or delayed expression of SRY results in XY gonadal sex reversal, accurate regulation of SRY is critical for male development in XY animals. In humans, dysregulation of SRY may cause disorders of sex development. Mouse Sry is the most intensively studied mammalian model of sex determination. Sry expression is controlled in a spatially and temporally stringent manner. Several transcription factors play a key role in sex determination as trans-acting factors for Sry expression. In addition, recent studies have shown that several epigenetic modifications of Sry are involved in sex determination as cis-acting factors for Sry expression. Herein, we review the current understanding of transcription factor- and epigenetic modifier-mediated regulation of SRY/Sry expression. [ABSTRACT FROM AUTHOR]

The mammalian Y chromosome has evolved in many species into a specialized chromosome that contributes to sex development among other male phenotypes. This function is well studied in terms of protein-coding genes. Less is known about the noncoding genome on the Y chromosome and its contribution to both sex development and other traits. Once considered junk genetic material, noncoding RNAs are now known to contribute to the regulation of gene expression and to play an important role in refining cellular functions. The prime examples are noncoding genes on the X chromosome, which mitigate the differential dosage of genes on sex chromosomes. Here, we discuss the evolution of noncoding RNAs on the Y chromosome and the emerging evidence of how micro, long, and circular noncoding RNAs transcribed from the Y chromosome contribute to sex differentiation. We briefly touch on emerging evidence that these noncoding RNAs also contribute to some other important clinical phenotypes in humans. [ABSTRACT FROM AUTHOR]

The rare condition 46, XY disorders of sex development (DSDs) is characterized by the female phenotype and male karyotype. We aimed to describe the genetic basis of 46, XY DSDs in nine patients and the genotype–phenotype relationships of the genes involved. Targeted next-generation sequencing (NGS) was used to analyze the underlying hereditary etiology in nine female patients with 46, XY DSDs. In silico analyses were used to predict the effects of novel variants on the protein function of the identified genes. Primary amenorrhea with the absence of puberty, inguinal hernia, and clitoridauxe were common complaints. All enrolled patients had a differential etiology by genetic testing, and five novel genetic variants involved in four genes (SRY, AR, NR5A1, and LHCGR) were identified. A novel nonsense variant of SRY c.51C > G was found in XY patients without testicles. Two novel heterozygous variants, i.e. c.265A > T (Ile89Leu) and c.422T > C (Val141Ala), of the LHCGR gene were found in male pseudo-hermaphroditism. We expanded the genetic mutation spectrum and described in detail the genotype–phenotype relationships of 46, XY DSDs. DNA sequencing for SRY should be a priority in female patients with 46, XY DSDs. NGS is useful for clarifying genetic pathogenesis and could provide a basis for clinical diagnosis and treatments of patients with 46, XY DSDs. [ABSTRACT FROM AUTHOR]

For the first time, a comparative study of haplotype and nucleotide diversity, genetic differentiation, and phylogeny of Tuvan woolly (two populations, n = 34) and Mongolian cashmere goats (five populations, n = 94) was carried out on the basis of polymorphisms of the hypervariable region of the mtDNA D‑loop and the SRY gene. An intrabreed, including interpopulation, analysis was carried out in comparison with the reference sequences of goats of other breeds. A high level of genetic diversity of the studied samples was revealed. The assessment of molecular variance showed that the main contribution to the genetic diversity of the studied breeds is made by intrapopulation diversity (98.84%) and only 1% is due to interbreed differences. The most common among Mongolian and Tuvan goats was haplogroup A of mtDNA; individuals belonging to haplogroups C and F were also found; other haplogroups (B, D, and G) were not found in these samples. Most of the males of the Mongolian breed on the basis of the SRY gene polymorphism had haplotypes Y1A (66.7%) and Y2A (25%); in the populations of Altai Ulaan and Three Beauties, individuals with a rare haplotype Y2B (8.3%) were identified. All studied males of the Tuvan breed of goats belonged to the Y2A haplotype. [ABSTRACT FROM AUTHOR]

Fragmentary bone in disaster victim identification is reliant on a robust and objective method. Current methods employing traditional phenotypic analysis for sex estimation of forensic fetal remains are limited and often not possible due to the lack of distinctive cranial and pelvic traits. Thus, a molecular sex estimation method optimized for bone samples would enhance current techniques. Sternal rib samples were dissected from unclaimed perinatal decedents, presenting at varied stages of decomposition and unconfirmed circumstances of death, who were admitted to the Johannesburg Forensic Pathology Service (JFPS) and included in the Johannesburg Forensic Paediatric Collection (JFPC). A molecular protocol was designed and optimized using genomic DNA from SW480 cells and five individuals of unknown provenance and known sex (estimated during medicolegal autopsy) by targeting the X-linked G6PD and Y-linked SRY genes. The sex estimated at autopsy was confirmed using the optimized protocol. Nine (9) unidentified individuals were included and assigned sex based on the method described. The development of a sex typing protocol targeting the G6PD and SRY loci provides a new PCR method for sex estimation of human remains from 25 mg of bone fragment.

Abstract Background 46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques. Case presentation We identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of the SRY gene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygous DAX1 mutation (c.498G > A, p.R166R), which was not previously reported in SRY-negative XX males. Conclusions We proposed that this synonymous DAX1 mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended for SRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.

Abstract Background Brain sexual differentiation is sculpted by precise coordination of steroid hormones during development. Programming of several brain regions in males depends upon aromatase conversion of testosterone to estrogen. However, it is not clear the direct contribution that Y chromosome associated genes, especially sex-determining region Y (Sry), might exert on brain sexual differentiation in therian mammals. Two species of spiny rats: Amami spiny rat (Tokudaia osimensis) and Tokunoshima spiny rat (T. tokunoshimensis) lack a Y chromosome/Sry, and these individuals possess an XO chromosome system in both sexes. Both Tokudaia species are highly endangered. To assess the neural transcriptome profile in male and female Amami spiny rats, RNA was isolated from brain samples of adult male and female spiny rats that had died accidentally and used for RNAseq analyses. Results RNAseq analyses confirmed that several genes and individual transcripts were differentially expressed between males and females. In males, seminal vesicle secretory protein 5 (Svs5) and cytochrome P450 1B1 (Cyp1b1) genes were significantly elevated compared to females, whereas serine (or cysteine) peptidase inhibitor, clade A, member 3 N (Serpina3n) was upregulated in females. Many individual transcripts elevated in males included those encoding for zinc finger proteins, e.g. zinc finger protein X-linked (Zfx). Conclusions This method successfully identified several genes and transcripts that showed expression differences in the brain of adult male and female Amami spiny rat. The functional significance of these findings, especially differential expression of transcripts encoding zinc finger proteins, in this unusual rodent species remains to be determined.

We have used the four core genotypes (FCG) mouse model, which allows a distinction between effects of gonadal secretions and chromosomal complement, to determine when sex differences in the immune system first appear and what influences their development. Using splenic T cell number as a measure that could be applied to neonates with as yet immature immune responses, we found no differences among the four genotypes at postnatal day 1, but by day 7, clear sex differences were observed. These sex differences were unexpectedly independent of chromosomal complement and similar in degree to gonadectomized FCG adults: both neonatal and gonadectomized adult females (XX and XY) showed 2-fold the number of CD4+ and 7-fold the number of CD8+ T cells versus their male (XX and XY) counterparts. Appearance of this long-lived sex difference between days 1 and 7 suggested a role for the male-specific perinatal surge of testicular testosterone. Interference with the testosterone surge significantly de-masculinized the male CD4+, but not CD8+ splenic profile. Treatment of neonates demonstrated elevated testosterone limited mature cell egress from the thymus, whereas estradiol reduced splenic T cell seeding in females. Neonatal male splenic epithelium/stroma expressed aromatase mRNA, suggesting capacity for splenic conversion of perinatal testosterone into estradiol in males, which, similar to administration of estradiol in females, would result in reduced splenic T cell seeding. These sex steroid effects affected both CD4+ and CD8+ cells and yet interference with the testosterone surge only significantly de-masculinized the splenic content of CD4+ cells. For CD8+ cells, male cells in the thymus were also found to express one third the density of sphingosine-1-phosphate thymic egress receptors per cell compared to female, a male characteristic most likely an indirect result of Sry expression. Interestingly, the data also support a previously unrecognized role for non-gonadal estradiol in the promotion of intra-thymic cell proliferation in neonates of both sexes. Microarray analysis suggested the thymic epithelium/stroma as the source of this hormone. We conclude that some immune sex differences appear long before puberty and more than one mechanism contributes to differential numbers and distribution of T cells.

Fetal alcohol exposure (FAE) causes various neurodevelopmental deficits in offspring, including reduced expression of the stress regulatory proopiomelanocortin (Pomc) gene and an elevated stress response for multiple generations via the male germline. Male germline-specific effects of FAE on the Pomc gene raises the question if the sex-determining region Y (SRY) may have a role in regulating Pomc gene expression. Using a transgenerational model of FAE in Fischer 344 rats, we determined the role of SRY in the regulation of the Pomc gene. FAEs, like on the Pomc gene, reduced Sry gene expression in sperm and the mediobasal hypothalamus (MBH) in male adult offspring. Fetal alcohol-induced inhibition of Sry gene expression was associated with increased Sry promoter DNA methylation. Additionally, fetal alcohol effects on the Sry gene persisted for three generations in the male germline but not in the female germline. Sry gene knockdown reduced the Pomc gene expression. Sry recruitment onto the Pomc promoter was found to be reduced in the hypothalamus of fetal alcohol-exposed rats compared to control rats. Pomc promoter luciferase activity was increased following Sry overexpression. A site-directed mutagenesis study revealed that SRY binding sites are required for POMC promoter transcription activity. Overall, these findings suggest that SRY plays a stimulatory role in the regulation of Pomc gene expression and may potentially contribute to the fetal alcohol-induced changes in the level of Pomc gene expression for multiple generations.