Talk:Y Chromosome

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Cite this page: Hill, M.A. (2021, December 2) Embryology Y Chromosome. Retrieved from


Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes

Ortega EA, Salvador Q, Fernandez M & Ward MA. (2018). Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes. Biol. Reprod. , , . PMID: 30285093 DOI.

Ortega EA1, Salvador Q1, Fernandez M1, Ward MA1. Author information Abstract We previously demonstrated that in the mouse only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination. Timed-pregnancies were generated to obtain transgenic XEif2s3yOSry, XEif2s3yOSox9, XOSry, Eif2s3x, XOSox9, Eif2s3x and wild-type XX and XY fetuses at 12.5 days post coitum. Dissected genital ridges were assessed for their morphology and anatomy, and expression of pro-testis and pro-ovary transcripts. All transgenic males displayed incomplete masculinization of gonadal shape, impaired development of testicular cords and gonadal vasculature, and decreased expression of factors promoting male pathway. Fetal gonad masculinization was more effective when sex determination was driven by the Sry transgene, in the presence of Y chromosome genes, and to a lesser extent a double dosage of X genes. The study adds to the understanding of the role of Y chromosome genes and their homologues during sex determination. PMID: 30285093 DOI: 10.1093/biolre/ioy218


Chromosomal abnormality in men with impaired spermatogenesis

Int J Fertil Steril. 2014 Apr;8(1):35-42. Epub 2014 Mar 9. Mierla D1, Jardan D2, Stoian V3. Author information

Abstract BACKGROUND: Chromosomal abnormalities and Y chromosome microdeletions are regarded as two most frequent genetic causes associated with failure of spermatogenesis in the Caucasian population. MATERIALS AND METHODS: To investigate the distribution of genetic defects in the Romanian population with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 850 idiopathic infertile men and in 49 fertile men with one or more children. Screening for microdeletions in the azoospermia factor (AZF) region of Y chromosome was performed by multiplex polymerase chain reaction (PCR) on a group of 67 patients with no detectable chromosomal abnormality. The results of the two groups were compared by a two-tailed Fisher's exact test. RESULTS: In our study chromosomal abnormalities were observed in 12.70% and 8.16% of infertile and fertile individuals respectively. CONCLUSION: Our data suggests that infertile men with severe azoospermia have higher incidences of genetic defects than fertile men and also patients from any other group. Infertile men with normal sperm present a higher rate of polymorphic variants. It is important to know whether there is a genetic cause of male infertility before patients are subjected to intracytoplasmic sperm injection (ICSI) or testicular sperm extraction (TESE)/ICSI treatment. KEYWORDS: Azoospermia, Chromosomal Abnormality, Chromosome Microdeletion, Male Infertility, Oligozoospermia

PMID 24696767


Meiotic sex chromosome inactivation is disrupted in sterile hybrid male house mice

Genetics. 2013 Mar;193(3):819-28. doi: 10.1534/genetics.112.148635. Epub 2013 Jan 10.

Campbell P1, Good JM, Nachman MW. Author information

Abstract In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wild-derived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F1 males with a M. m. musculus mother are sterile or nearly so while F1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that trans-acting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis.

PMID 23307891


Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca2+ as a switch

FASEB J. 2010 Nov 4.

Kaur G, Jans DA.

  • Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia; and.


The sex-determining region on the Y chromosome (SRY) has 2 nuclear localization signals (NLSs) that flank the DNA binding high mobility group (HMG) domain; the β-NLS and the CaM-NLS, which mediate nuclear transport through importin β1 (Impβ1) and the calcium-binding protein calmodulin (CaM), respectively. Here we reconstitute the nuclear import mediated by the 2 NLSs for the first time in vitro, establishing Ran independence of CaM-NLS-dependent transport. The β- and CaM-NLSs were found to be independently functional out of the context of the SRY HMG domain, dependent on Impβ1 and CaM binding, respectively. Intriguingly, direct protein binding assays also indicated competitive binding of Impβ1 and CaM to the SRY HMG domain. To assess the potential role of intracellular calcium in modulating SRY nuclear accumulation, Cos-7 cells expressing SRY and control constructs were treated with agents elevating or reducing intracellular Ca(2+) levels. The in vivo results, supported by experiments in vitro where transport was assessed with or without 2 μ M Ca(2+), indicate a Ca(2+)-dependent mode of nuclear transport via the CaM-NLS/CaM, with inhibition of β-NLS/Impβ1-mediated nuclear import by intracellular Ca(2+). The results imply mutual exclusivity of nuclear transport via the 2 NLSs with intracellular Ca(2+) as the switch between the 2.-Kaur, G. Jans, D. A. Dual nuclear import mechanisms of sex determining factor SRY: intracellular Ca(2+) as a switch.

PMID: 21051653

Testis-specific protein on Y chromosome (TSPY) represses the activity of the androgen receptor in androgen-dependent testicular germ-cell tumors

Proc Natl Acad Sci U S A. 2010 Nov 1.

Akimoto C, Ueda T, Inoue K, Yamaoka I, Sakari M, Obara W, Fujioka T, Nagahara A, Nonomura N, Tsutsumi S, Aburatani H, Miki T, Matsumoto T, Kitagawa H, Kato S.

The Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Abstract

Testis-specific protein on Y chromosome (TSPY) is an ampliconic gene on the Y chromosome, and genetic interaction with gonadoblastoma has been clinically established. However, the function of the TSPY protein remains to be characterized in physiological and pathological settings. In the present study, we observed coexpression of TSPY and the androgen receptor (AR) in testicular germ-cell tumors (TGCTs) in patients as well as in model cell lines, but such coexpression was not seen in normal testis of humans or mice. TSPY was a repressor for androgen signaling because of its trapping of cytosolic AR even in the presence of androgen. Androgen treatment stimulated cell proliferation of a TGCT model cell line, and TSPY potently attenuated androgen-dependent cell growth. Together with the finding that TSPY expression is reduced in more malignant TGCTs in vivo, the present study suggests that TSPY serves as a repressor in androgen-induced tumor development in TGCTs and raises the possibility that TSPY could be used as a clinical marker to assess the malignancy of TGCTs.

PMID: 21041627

Semen quality in men with Y chromosome aberrations

Int J Androl. 2010 Oct 6. doi: 10.1111/j.1365-2605.2010.01108.x. [Epub ahead of print]

Antonelli A, Marcucci L, Elli R, Tanzi N, Paoli D, Radicioni A, Lombardo F, Lenzi A, Gandini L.

Departments of Cellular Biotechnology and Haematology Medical Pathophysiology, University of Rome 'La Sapienza', Rome, Italy. Abstract

Infertile males sometimes bear structurally balanced chromosome aberrations, such as translocations and inversions, which involve both autosomes and sex chromosomes. The aim of this study was to evaluate genotype-phenotype correlations in a sample of infertile men with various types of Y chromosome abnormalities. In particular, we examined the effect of (i) balanced structural aberrations such as translocations between sex chromosomes and autosomes; (ii) unbalanced structural aberrations such as deletions or isodicentrics, both [idic(Yp)] and [idic(Yq)]. We studied 13 subjects bearing Y chromosome aberrations. Each patient underwent seminal fluid examination, andrological inspection, hormone study, testicular ultrasound, conventional and molecular cytogenetic analysis and study of Y chromosome microdeletions. Comparison of genotype and sperm phenotype in infertile patients with various Y chromosome aberrations revealed the key role of meiotic pairing defects in arresting spermatogenesis, both in the presence and in the absence of azoospermic factor microdeletions and cell mosaicism. The failure of meiosis and, in consequence, spermatogenesis may be a result of the failure to inactivate the X chromosome in the meiotic prophase, which is necessary for normal male spermatogenesis to take place.

© 2010 The Authors International Journal of Andrology © 2010 European Academy of Andrology.

PMID: 21039604

Y chromosome in Turner syndrome: review of the literature

Sao Paulo Med J. 2009 Nov;127(6):373-8. Oliveira RM, Verreschi IT, Lipay MV, Eça LP, Guedes AD, Bianco B.

Centro de Extensão Universitária, São Paulo, Brazil. Abstract Turner syndrome (TS) is one of the most common types of aneuploidy among humans, and is present in 1:2000 newborns with female phenotype. Cytogenetically, the syndrome is characterized by sex chromosome monosomy (45,X), which is present in 50-60% of the cases. The other cases present mosaicism, with a 45,X cell line accompanied by one or more other cell lines with a complete or structurally abnormal X or Y chromosome. The presence of Y-chromosome material in patients with dysgenetic gonads increases the risk of gonadal tumors, especially gonadoblastoma. The greatest concern is the high risk of developing gonadoblastoma or other tumors and virilization during puberty if chromosome Y-specific sequences are present. The role of the Y chromosome in human oncogenesis is still controversial. Even though gonadoblastoma is a benign tumor, it can undergo transformation into invasive dysgerminoma in 60% of the cases, and also into other, malignant forms of germ cell tumors. Although some authors have questioned the high incidence of gonadoblastoma (around 30%), the risk of developing any kind of gonadal lesion, whether tumoral or not, justifies investigation of Y-chromosome sequences by means of the polymerase chain reaction (PCR), a highly sensitive, low-cost and easy-to-perform technique. In conclusion, mosaicism of both the X and the Y chromosome is a common finding in TS, and detection of Y-chromosome-specific sequences in patients, regardless of their karyotype, is necessary in order to prevent the development of gonadal lesions.

PMID: 20512293


Sex determination and gonadal development in mammals

Physiol Rev. 2007 Jan;87(1):1-28.

Wilhelm D, Palmer S, Koopman P.

Division of Molecular Genetics and Development and Australian Research Council Centre of Excellence in Biotechnology and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.

Abstract Arguably the most defining moment in our lives is fertilization, the point at which we inherit either an X or a Y chromosome from our father. The profoundly different journeys of male and female life are thus decided by a genetic coin toss. These differences begin to unfold during fetal development, when the Y-chromosomal Sry ("sex-determining region Y") gene is activated in males and acts as a switch that diverts the fate of the undifferentiated gonadal primordia, the genital ridges, towards testis development. This sex-determining event sets in train a cascade of morphological changes, gene regulation, and molecular interactions that directs the differentiation of male characteristics. If this does not occur, alternative molecular cascades and cellular events drive the genital ridges toward ovary development. Once testis or ovary differentiation has occurred, our sexual fate is further sealed through the action of sex-specific gonadal hormones. We review here the molecular and cellular events (differentiation, migration, proliferation, and communication) that distinguish testis and ovary during fetal development, and the changes in gene regulation that underpin these two alternate pathways. The growing body of knowledge relating to testis development, and the beginnings of a picture of ovary development, together illustrate the complex mechanisms by which these organ systems develop, inform the etiology, diagnosis, and management of disorders of sexual development, and help define what it is to be male or female.

PMID: 17237341