H-Y antigen

Last updated
anti-Müllerian hormone
Identifiers
SymbolAMH
NCBI gene 268
HGNC 464
OMIM 600957
RefSeq NM_000479
UniProt P03971
Other data
Locus Chr. 19 p13.3
Search for
Structures Swiss-model
Domains InterPro
Lysine-Specific Demethylase 5D protein
Identifiers
SymbolKDM5D
Alt. symbolsHYA, SMCY
HGNC 11115
OMIM 426000
RefSeq NM_004653
UniProt Q9BY66
Other data
Locus Chr. Y q11.223
Search for
Structures Swiss-model
Domains InterPro
Male Enhanced Antigen 1
Identifiers
SymbolMEA1
Alt. symbolsHYS
HGNC 6986
OMIM 143170
RefSeq NM_001318942
UniProt Q16626
Other data
Locus Chr. 6 p21.1
Search for
Structures Swiss-model
Domains InterPro

H-Y antigen is a male tissue specific antigen. [1] Originally thought to trigger the formation of testes (via loci, an autosomal gene that generates the antigen and one that generates the receptor) [2] it is now known that it does not trigger the formation of testes but may be activated by the formation of testes. [3]

Contents

There are several antigens which qualify as H-Y as defined by rejection of male skin grafts in female hosts or detected by cytotoxic T cells or antibodies. One H-Y, secreted by the testis, defined by antibodies, is identical to Müllerian-inhibiting substance (AMH gene). [1] Another H-Y, minor histocompatibility antigen, seemed to be encoded in the SMCY gene (acronym for 'selected mouse cDNA on Y'), later identified as an 11-residue peptide from the Lysine-Specific Demethylase 5D protein (KDM5D gene) presented by HLA-B7. A third example is MEA1.

Association with spermatogenesis

It has been shown that male mice lacking in the H-Y antigen, hence lacking in the gene producing it, have also lost genetic information responsible for spermatogenesis. [4] This result also identified a gene on the mouse Y chromosome, distinct from the testis-determining gene, that was essential for spermatogenesis, thus raising the possibility that the very product of this "spermatogenesis gene" is the H-Y antigen. [4]

Male homosexuality and the birth order effect

Among humans, it has been observed that men with more older brothers tend to have a higher chance of being homosexual (see Fraternal birth order and male sexual orientation). For every additional older brother, a man's chance of being homosexual can rise by up to 33%. [5] One theory to explain this involves H-Y antigens, which suggests that a maternal immune reaction to these antigens has, to an extent, an inhibitory effect on the masculinization of the brain, and therefore, the more male foetuses that the mother of a man has had, the greater the maternal immune response towards him [6] and thus the greater the inhibitory effect on brain masculinization, which is believed to be a factor in sexual orientation. [5]

This hypothesis is supported by evidence that older sisters have no discernible influence on the sexual orientation of later-born males, which would be expected since H-Y antigen is male tissue specific, the 'probable involvement of H-Y antigen in the development of sex-typical traits, and the detrimental effects of immunization of female mice to H-Y antigen on the reproductive performance of subsequent male offspring'. [7] More specifically, recent research (Jan 2018) has found maternal antibodies to the neuroligin NLGN4Y protein, a Y-chromosome protein important in male fetal brain development, to be involved in the fraternal birth order effect. [8]

Related Research Articles

<span class="mw-page-title-main">Biology and sexual orientation</span> Field of sexual orientation research

The relationship between biology and sexual orientation is a subject of on-going research. While scientists do not know the exact cause of sexual orientation, they theorize that it is caused by a complex interplay of genetic, hormonal, and environmental influences. Hypotheses for the impact of the post-natal social environment on sexual orientation, however, are weak, especially for males.

<span class="mw-page-title-main">X chromosome</span> Sex chromosome present in both sexes in the XY and X0 sex-determination systems

The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its unique properties by early researchers, which resulted in the naming of its counterpart Y chromosome, for the next letter in the alphabet, following its subsequent discovery.

<span class="mw-page-title-main">Spermatogenesis</span> Production of sperm

Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules. These cells are called spermatogonial stem cells. The mitotic division of these produces two types of cells. Type A cells replenish the stem cells, and type B cells differentiate into primary spermatocytes. The primary spermatocyte divides meiotically into two secondary spermatocytes; each secondary spermatocyte divides into two equal haploid spermatids by Meiosis II. The spermatids are transformed into spermatozoa (sperm) by the process of spermiogenesis. These develop into mature spermatozoa, also known as sperm cells. Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the two secondary spermatocytes by their subdivision produce four spermatozoa and four haploid cells.

<span class="mw-page-title-main">Sertoli cell</span> Cells found in human testes which help produce sperm

Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis as a structural component of the seminiferous tubules. They are activated by follicle-stimulating hormone (FSH) secreted by the adenohypophysis and express FSH receptor on their membranes.

<span class="mw-page-title-main">Sex-determining region Y protein</span> Protein that initiates male sex determination in therian mammals

Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.

<span class="mw-page-title-main">Fraternal birth order and male sexual orientation</span> Theory of sexual orientation

Fraternal birth order has been correlated with male sexual orientation, with a significant volume of research finding that the more older brothers a male has from the same mother, the greater the probability he will have a homosexual orientation. Ray Blanchard and Anthony Bogaert first identified the association in the 1990s and named it the fraternal birth order effect. Scientists have attributed the effect to a prenatal biological mechanism, since the association is only present in men with older biological brothers, and not present among men with older step-brothers and adoptive brothers. The mechanism is thought to be a maternal immune response to male fetuses, whereby antibodies neutralize male Y-proteins thought to play a role in sexual differentiation during development. This would leave some regions of the brain associated with sexual orientation in the 'female typical' arrangement – or attracted to men. Biochemical evidence for this hypothesis was identified in 2017, finding mothers with a gay son, particularly those with older brothers, had heightened levels of antibodies to the NLGN4Y Y-protein than mothers with heterosexual sons.

<span class="mw-page-title-main">Ray Blanchard</span> American-Canadian sexologist

Ray Milton Blanchard is an American-Canadian sexologist who researches pedophilia, sexual orientation and gender identity. He has found that men with more older brothers are more likely to be gay than men with fewer older brothers, a phenomenon he attributes to the reaction of the mother's immune system to male fetuses. Blanchard has also published research studies on phallometry and several paraphilias, including autoerotic asphyxia. Blanchard also proposed a typology of transsexualism.

A relationship between handedness and sexual orientation has been suggested by a number of researchers, who report that heterosexual individuals are somewhat more likely to be right-handed than are homosexual individuals.

Xq28 is a chromosome band and genetic marker situated at the tip of the X chromosome which has been studied since at least 1980. The band contains three distinct regions, totaling about 8 Mbp of genetic information. The marker came to the public eye in 1993 when studies by Dean Hamer and others indicated a link between the Xq28 marker and male sexual orientation.

<span class="mw-page-title-main">Minor histocompatibility antigen</span>

Minor histocompatibility antigen are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens (MiHAs) are diverse, short segments of proteins and are referred to as peptides. These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. Peptide sequences can differ among individuals and these differences arise from SNPs in the coding region of genes, gene deletions, frameshift mutations, or insertions. About a third of the characterized MiHAs come from the Y chromosome. Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. These endogenous or self peptides are then transported into the endoplasmic reticulum with a peptide transporter pump called TAP where they encounter and bind to the MHC class I molecule. This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells.

Certain sites of the mammalian body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Tissue grafts are normally recognised as foreign antigens by the body and attacked by the immune system. However, in immune privileged sites, tissue grafts can survive for extended periods of time without rejection occurring. Immunologically privileged sites include:

<span class="mw-page-title-main">KDM5D</span> Protein-coding gene in the species Homo sapiens

Lysine-specific demethylase 5D is an enzyme that in humans is encoded by the KDM5D gene. KDM5D belongs to the alpha-ketoglutarate-dependent hydroxylases superfamily.

Testicular Immunology is the study of the immune system within the testis. It includes an investigation of the effects of infection, inflammation and immune factors on testicular function. Two unique characteristics of testicular immunology are evident: (1) the testis is described as an immunologically privileged site, where suppression of immune responses occurs; and, (2) some factors which normally lead to inflammation are present at high levels in the testis, where they regulate the development of sperm instead of promoting inflammation.

<span class="mw-page-title-main">Sperm-associated antigen 8</span> Protein-coding gene in the species Homo sapiens

Sperm-associated antigen 8 is a protein that in humans is encoded by the SPAG8 gene.

<span class="mw-page-title-main">Sperm protein associated with the nucleus, X-linked, family member A1</span> Protein-coding gene in the species Homo sapiens

Sperm protein associated with the nucleus on the X chromosome A is a protein that in humans is encoded by the SPANXA1 gene.

<span class="mw-page-title-main">Neuroligin</span> Protein

Neuroligin (NLGN), a type I membrane protein, is a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons. Neuroligins act as ligands for β-neurexins, which are cell adhesion proteins located presynaptically. Neuroligin and β-neurexin "shake hands", resulting in the connection between two neurons and the production of a synapse. Neuroligins also affect the properties of neural networks by specifying synaptic functions, and they mediate signalling by recruiting and stabilizing key synaptic components. Neuroligins interact with other postsynaptic proteins to localize neurotransmitter receptors and channels in the postsynaptic density as the cell matures. Additionally, neuroligins are expressed in human peripheral tissues and have been found to play a role in angiogenesis. In humans, alterations in genes encoding neuroligins are implicated in autism and other cognitive disorders. Antibodies in a mother from previous male pregnancies against neuroligin 4 from the Y chromosome increase the probability of homosexuality in male offspring.

<span class="mw-page-title-main">Environment and sexual orientation</span> Field of sexual orientation research

The relationship between the environment and sexual orientation is a subject of research. In the study of sexual orientation, some researchers distinguish environmental influences from hormonal influences, while other researchers include biological influences such as prenatal hormones as part of environmental influences.

<span class="mw-page-title-main">Neuroscience and sexual orientation</span> Mechanisms of sexual orientation development in humans

Sexual orientation is an enduring pattern of romantic or sexual attraction to persons of the opposite sex or gender, the same sex or gender, or to both sexes or more than one gender, or none of the aforementioned at all. The ultimate causes and mechanisms of sexual orientation development in humans remain unclear and many theories are speculative and controversial. However, advances in neuroscience explain and illustrate characteristics linked to sexual orientation. Studies have explored structural neural-correlates, functional and/or cognitive relationships, and developmental theories relating to sexual orientation in humans.

<span class="mw-page-title-main">Prenatal hormones and sexual orientation</span> Hormonal theory of sexuality

The hormonal theory of sexuality holds that, just as exposure to certain hormones plays a role in fetal sex differentiation, such exposure also influences the sexual orientation that emerges later in the individual. Prenatal hormones may be seen as the primary determinant of adult sexual orientation, or a co-factor with genes, biological factors and/or environmental and social conditions.

Cancer/testis (CT) antigens are a group of proteins united by their importance in development and in cancer immunotherapy. In general, expression of these proteins is restricted to male germ cells in the adult animal. However, in cancer these developmental antigens are often re-expressed and can serve as a locus of immune activation. Thus, they are often classified as tumor antigens. The expression of CT antigens in various malignancies is heterogeneous and often correlates with tumor progression. CT antigens have been described in melanoma, liver cancer, lung cancer, bladder cancer, and pediatric tumors such as neuroblastoma. Gametogenesis offers an important role for many of these antigens in the differentiation, migration, and cell division of primordial germ cells, spermatogonia spermatocytes and spermatids. Because of their tumor-restricted expression and strong in vivo immunogenicity, CT antigens are identified as ideal targets for tumor specific immunotherapeutic approaches and prompted the development of several clinical trials of CT antigens-based vaccine therapy. CT antigens have been found to have at least 70 families so far, including about 140 members, most of which are expressed during spermatogenesis. Their expression are mainly regulated by epigenetic events, specifically, DNA methylation.

References

  1. 1 2 Müller U (June 1996). "H-Y antigens". Human Genetics. 97 (6): 701–4. doi:10.1007/BF02346175. PMID   8641682. S2CID   25641671.
  2. "H-Y Antigen". mediLexicon. Wolters Kluwer. Archived from the original on 2017-11-30.
  3. Wolf U (1998). "The serologically detected H-Y antigen revisited". Cytogenetics and Cell Genetics. 80 (1–4): 232–5. doi:10.1159/000014986. PMID   9678364. S2CID   25908189.
  4. 1 2 Burgoyne PS, Levy ER, McLaren A (1986). "Spermatogenic failure in male mice lacking H-Y antigen". Nature. 320 (6058): 170–2. Bibcode:1986Natur.320..170B. doi:10.1038/320170a0. PMID   3951555. S2CID   4284719.
  5. 1 2 Ridley M (2000). Genome: The Autobiography of a Species in 23 Chapters. Harper and Collins. ISBN   978-0-06-089408-5.
  6. Dare T (8 October 2013). "Vaccination and immunity for iGCSE Biology". YouTube.
  7. Blanchard R, Klassen P (April 1997). "H-Y antigen and homosexuality in men". Journal of Theoretical Biology. 185 (3): 373–8. Bibcode:1997JThBi.185..373B. CiteSeerX   10.1.1.602.8423 . doi:10.1006/jtbi.1996.0315. PMID   9156085.
  8. Bogaert AF, Skorska MN, Wang C, Gabrie J, MacNeil AJ, Hoffarth MR, VanderLaan DP, Zucker KJ, Blanchard R (January 2018). "Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y". Proceedings of the National Academy of Sciences of the United States of America. 115 (2): 302–306. Bibcode:2018PNAS..115..302B. doi: 10.1073/pnas.1705895114 . PMC   5777026 . PMID   29229842.