Skip to main content
SpringerLink
Log in

Variability in serologically detected male antigen titer and some resulting problems: A critical review

  • Review Articles
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

“Serologically detected male antigen” (also called H-Y antigen) was first described in normal male mammals but now appears to occur in normal female mammals as well. “Serologically detected male predominant” (SDMP) antigen is a more appropriate name since the titer in normal males usually exceeds that of normal females. As we show, in each sex there is a considerable inter-individual variability in SDMP antigen titer, and in moderate-to-large size samples the low end of the male range of titers usually coincides with the high end of the female range.

Several major problems arise from failure to recognize and/or to deal adequately with this normal variation in SDMP antigen titer. The chief problem is that the “controls” used (often a single individual) may be inadequate and misleading, leading to unjustified designation of samples as “positive”, “negative”, or even “deviant” (“intermediate”, “reduced”) for SDMP antigen titer. Other problems include deficiencies in technique and lack of statistical control for test and sample variability. Adequate attention to these problems, especially to the normal variability in SDMP antigen titer, could reduce the contradictions and inconsistencies which have troubled this field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altman PL, Dittmer DS (eds) (1972) Biology data book, 2nd edn, 3 vols. Federation of American Societies for Experimental Biology, Bethesda

    Google Scholar 

  • Amice-Chambon V, Amice J, Genetet B (1981) Evidence of H-Y antigen on human B lymphocytes. Ann Immunol (Paris) 132 C:157–165

    Google Scholar 

  • Benhaim A, Gangnerau MN, Bettane-Casanova M, Fellous M, Picon R (1982) Effects of H-Y antigen on morphologic and endocrine differentiation of gonads in mammals. Differentiation 22:53–58

    Google Scholar 

  • Bennett D, Mathieson BJ, Scheid M, Yanagisawa K, Boyse EA, Wachtel SS, Cattanach BM (1977) Serological evidence for H-Y antigen in Sxr,XX sex-reversed phenotypic males. Nature 265:255–257

    Google Scholar 

  • Bernstein R, Koo GC, Wachtel SS (1980) Abnormality of the X chromosome in human 46,XY female siblings with dysgenetic ovaries. Science 207:768–769

    Google Scholar 

  • Billingham RE, Silvers WK (1960) Studies on tolerance of the Y chromosome antigen in mice. J Immunol 85:14–26

    Google Scholar 

  • Breg WR, Genel M, Koo GC, Wachtel SS, Krupen-Brown K, Miller O (1979) H-Y antigen and human chromosomal abnormalities. In: Vallet HL, Porter IH (eds) Genetic mechanisms of sexual development. Academic Press, New York London, pp 279–291

    Google Scholar 

  • Bricarelli DF, Fraccaro M, Lindsten J, Müller U, Baggio P, Carbone LDL, Hjerpe A, Lindgren F, Mayerová A, Ringertz H, Ritzén EM, Rovetta DC, Sicchero C, Wolf U (1981) Sex-reversed XY females with campomelic dysplasia are H-Y negative. Hum Genet 57:15–22

    Google Scholar 

  • Burgoyne PS (1982) Genetic homology and crossing over in the X and Y chromosomes of mammals. Hum Genet 61:85–90

    Google Scholar 

  • Casanova-Bettane M, Fellous M (1981) Antigene H-Y et dysgenesies sexuelles chez l'homme. CR Soc Biol (Paris) 175:8–18

    Google Scholar 

  • Casanova-Bettane M, Latron F, Jakob H, Fellous M (1981) A quantitative radioimmunoassay for membranous and soluble H-Y antigen typing. Hum Genet 58:21–24

    Google Scholar 

  • Cattanach MB, Evans EP, Burtenshaw MD, Barlow J (1982) Male, female and intersex development in mice of identical chromosome constitution. Nature 300:445–476

    Google Scholar 

  • Celada F, Welshons WJ (1963) Immunogenetic analysis of the male antigen in mice utilizing animals with an exceptional chromosome constitution. Genetics 48:139–156

    Google Scholar 

  • Coulam CB, Gallenberg MM, Webb MJ, Gaffey TA (1982) The absence of H-Y antigen in XY gonads grossly resembling ovaries. Am J Obstet Gynecol 142:925–927

    Google Scholar 

  • Davis MD (1981) Localization of male-determining factors in man: a thorough review of structural anomalies of the Y chromosome. J Med Genet 18:161–195

    Google Scholar 

  • de la Chapelle A (1981) The etiology of maleness in XX men. Hum Genet 58:105–116

    Google Scholar 

  • de la Chapelle A, Koo GC, Wachtel SS (1978) Recessive sex-determining genes in human XX male syndrome. Cell 15:837–842

    Google Scholar 

  • Dorus E, Amarose AP, Koo GC, Wachtel SS (1977) Clinical pathological and genetic findings in a case of 46,XY pure gonadal dysgenesis (Swyer's syndrome). II. Presence of H-Y antigen. Am J Obstet Gynecol 127:829–831

    Google Scholar 

  • Eicher EM (1982) In: Prospect for sexing mammalian sperm. Colorado Associated University Press, Boulder, pp 121–135

    Google Scholar 

  • Eichwald EJ, Silmser CR (1955) Untitled communication. Transplant Bull 2:148–149

    Google Scholar 

  • Engel W, Klemme B, Ebrecht A (1981a) Serological evidence for H-Y antigen in XO-female mice. Hum Genet 57:67–70

    Google Scholar 

  • Engel W, Klemme H, Probeck D, Hansmann I (1981b) H-Y antigen in Turner's syndrome patients with different sex chromosome constitutions. Hum Genet 59:333–336

    Google Scholar 

  • Engel W, Klemme B, Probeck HD, Fonatsch C (1982) H-Y antigen in male patients with X polysomies. Hum Genet 61:110–112

    Google Scholar 

  • Evans EP, Burtenshaw MD, Cattanach BM (1982) Meiotic crossing-over between the X and Y chromosomes of male mice carrying the sex-reversing (Sxr) factor. Nature 300:443–445

    Google Scholar 

  • Faggiano M, Ferraro M, Criscuolo T, Sinisi AA, de Capoa A (1980) Cytological evidence for the location of male-determining and H-Y genes on the short arm of Y chromosome. Hum Genet 54:323–326

    Google Scholar 

  • Fraccaro M, Tiepolo L, Suffardi D, Chiumello G, DiNatale E, Gargantini G, Wolf U (1979) Familial XX true hermaphroditism and the H-Y antigen. Hum Genet 48:45–52

    Google Scholar 

  • Fraccaro M, Mayerová A, Wolf U, Bühler E, Gebauer J, Gilgenkrantz S, Lindsten J, Lo Curto F, Ritzén EM (1982) Correlation between the number of sex chromosomes and the H-Y antigen titer. Hum Genet 61:135–140

    Google Scholar 

  • Gasser DL (1980) H-Y antigen and sex determination. Am J Hum Genet 32:459–462

    Google Scholar 

  • Goldberg EH, Boyse EA, Bennett D, Scheid M, Carswell EA (1971) Serological demonstration of H-Y (male) antigen on mouse sperm. Nature 232:478–480

    Google Scholar 

  • Goodfellow PN, Andrews PW (1982) Sexual differentiation and H-Y antigen. Nature 295:11–13

    Google Scholar 

  • Gore-Langton RE, Tung PS, Fritz IB (1983) The absence of specific interactions of Sertoli cell-secreted proteins with antibodies directed against H-Y antigen. Cell 32:289–301

    Google Scholar 

  • Gosh SN, Shah PN, Gharpure HM (1978) Absence of H-Y antigen in XY females with dysgenetic gonads. Nature 276:180–181

    Google Scholar 

  • Hall JL, Wachtel SS (1980) Primary sex determination: genetics and biochemistry. Mol Cell Biochem 33:49–66

    Google Scholar 

  • Hammerton JL, Dickson JM, Pollard CE, Grieves SA, Short RV (1969) Genetic intersexuality in goats. J Reprod Fertil (Suppl) 7:25–51

    Google Scholar 

  • Haseltine FP, Breg WR, Koo GC, Wachtel SS, Genel M (1980) H-Y antigen expression in subjects with Turner phenotype and i(Xq). Annual Meeting of Society for Gyn Adv, Denver, Col, Abs No 223

  • Haseltine FP, De Ponte KK, Breg RW, Genel M (1982) Presence of H-Y antigen in patients with Ullrich-Turner syndrome and X-chromosome rearrangements. Am J Med Genet 11:97–107

    Google Scholar 

  • Koo GC (1981) Serology of H-Y antigen. Hum Genet 58:18–20

    Google Scholar 

  • Koo GC, Varano A (1981) Inhibition of H-Y cell-mediated cytolysis by monoclonal H-Y specific antibody. Immunogenetics 14:183–188

    Google Scholar 

  • Koo GC, Wachtel SS, Saenger PS, Nero NI, Dosik H, Amarose AP, Dorus E, Ventruto V (1977a) H-Y antigen: expression in human subjects with testicular feminization syndrome. Science 196:655–656

    Google Scholar 

  • Koo GC, Wachtel SS, Krupen-Brown K, Mittl LR, Breg WR, Genel M, Rosenthal JM, Borgaonkar DS, Miller DA, Tantravahi R, Schreck RR, Erlanger BF, Miller OJ (1977b) Mapping the locus of the H-Y gene on the human Y chromosome. Science 196:940–942

    Google Scholar 

  • Koo GC, Tada N, Chaganti R, Hammerling U (1981) Application of monoclonal anti H-Y antibody for human H-Y typing. Hum Genet 57:64–67

    Google Scholar 

  • McCarrey JR, Abbott UK (1979) Mechanism of genetic sex determination, gonadal sex differentiation, and germ-cell development in animals. Adv Genet 20:217–286

    Google Scholar 

  • McLaren A, Monk M (1982) Fertile females produced by inactivation of an X chromosome of “sex-reversed” mice. Nature 300:446–448

    Google Scholar 

  • Meade KW, Wachtel SS, Davis JR, Lightner ES (1981) H-Y antigen in XO/X,iso(X) mosaic Turner syndrome. Obstet Gynecol 57:594–599

    Google Scholar 

  • Melvold RW, Koln HI, Yerganian G, Fawcett DW (1977) Evidence suggesting the existence of two H-Y antigens in the mouse. Immunogenetics 5:33–41

    Google Scholar 

  • Moltz L, Schwartz U, Pickartz H, Hammerstein J, Wolf U (1981) XY gonadal dysgenesis: aberrant testicular differentiation in the presence of H-Y antigen. Obstet Gynecol 58:17–25

    Google Scholar 

  • Moreira-Filho CA, Toledo SPA, Bagnolli VR, Frota-Pessoa O, Wajntal A (1979) H-Y antigen in Swyer syndrome and the genetics of XY gonadal dysgenesis. Hum Genet 53:51–56

    Google Scholar 

  • Moreira-Filho CA, Otto PG, Mustachi Z, Frota-Pessoa O, Otto PA (1980) H-Y antigen expression in a case of XX true hermaphroditism. Hum Genet 55:309–314

    Google Scholar 

  • Müller U, Bross K (1979) A highly sensitive peroxidase-anti-peroxidase method for detection of H-Y antigen on cultivated human fibroblasts. Hum Genet 52:143–147

    Google Scholar 

  • Müller U, Urban E (1981) Reaggregation of rat gonadal cells in vitro: experiments on the function of H-Y antigen. Cytogenet Cell Genet 31:104–107

    Google Scholar 

  • Nazareth HRS, Moreira-Filho CA, Cunha AJB, Vieira-Filho JPB, Lengyel AMJ, Lima MC (1979) H-Y antigen in 46 XY pure testicular dysgenesis. Am J Med Genet 3:149–154

    Google Scholar 

  • Ohno S (1967) Sex chromosomes and sex-linked genes. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Ohno S, Nagai Y, Ciccarese S (1978) Testicular cells lysostripped of H-Y antigen organize ovarian-follicle-like aggregates. Cytogenet Cell Genet 20:351–364

    Google Scholar 

  • Passarge E, Wolf U (1981) Brief clinical report: Genetic heterogeneity of XY gonadal dysgenesis (Swyer syndrome): H-Y antigen negative XY gonadal dysgenesis associated with inflammatory bowel disease. Am J Med Genet 8:437–441

    Google Scholar 

  • Pearson ES, Hartley HO (eds) (1962) Biometrika tables for statisticians, vol 1, 2nd edn. Cambridge University Press, Cambridge, p 174

    Google Scholar 

  • Pickartz H, Moltz L, Altenahr L (1980) XY (H-Y+) gonadal dysgenesis. Virchows Arch [Pathol Anat] 389:103

    Google Scholar 

  • Polani PE, Adinolfi M (1983) The H-Y antigen and its functions: A review and a hypothesis. J Immunogenet 10:85–102

    Google Scholar 

  • Puck SM, Haseltine FP, Francke U (1981) Absence of H-Y antigen in an XY female with campomelic dysplasia. Hum Genet 57:23–27

    Google Scholar 

  • Race RR, Sanger R (1975) Blood groups in man, 6th edn. Blackwell Scientific Publications, Oxford Edinburgh Melbourne

    Google Scholar 

  • Rao CS, Vaidya RA, Ambani LM (1981a) Effects of maternal anti-H-Y antibodies on fetal gonadal development. J Reprod Immunol 3:175–185

    Google Scholar 

  • Rao CS, Vaidya RA, Ambani LM (1981b) Role of H-Y antigen in gonadal differentiation. Indian J Med Res 73:342–349

    Google Scholar 

  • Rosenfeld RG, Luzzatti L, Hintz RL, Miller OJ, Koo GC, Wachtel SS (1979) Sexual and somatic determinants of the human Y chromosome: Studies in 46,XYp phenotypic female. Am J Hum Genet 31:458–468

    Google Scholar 

  • Russell MH, Wachtel SS, Davis BW, Cahill LT, Gross E, Niblack GD, Burr IM (1982) Ovarian development in 46,XY gonadal dysgenesis. Hum Genet 60:196–199

    Google Scholar 

  • Savikurki H, Pajunen L, Nemlander A, Andersson LC, de la Chapelle A (1981) Radioimmunoassay for H-Y antigen. J Immunol Methods 41:343–349

    Google Scholar 

  • Selden JR, Wachtel SS, Koo GC, Haskins ME, Patterson DF (1978) Genetic basis of XX male syndrome and XX true hermaphroditism: evidence in the dog. Science 201:644–646

    Google Scholar 

  • Shapiro M, Erickson RP, Lewis S, Tres LL (1982) Serological and cytological evidence for increased Y-chromosome related material in Sxr,XY (sex-reversed carrier, male) mice. J Reprod Immunol 4:191–206

    Google Scholar 

  • Sharp AJ, Wachtel SS, Benirschke K (1980) H-Y antigen in a fertile XY female horse. J Reprod Fertil 58:157–160

    Google Scholar 

  • Short RV (1979) Sex determination and differentiation. Br Med Bull 35:121–127

    Google Scholar 

  • Silvers WK, Gasser DL, Eicher EM (1982) H-Y antigen, serologically detectable male antigen and sex determination. Cell 28:439–440

    Google Scholar 

  • Simpson E (1982) Sex reversal and sex determination. Nature 300:404–406

    Google Scholar 

  • Simpson JL, Blagowidow N, Martin AO (1981) XY gonadal dysgenesis: Genetic heterogeneity based upon clinical observations, H-Y antigen status and segregation analysis. Hum Genet 58:91–97

    Google Scholar 

  • Simpson E, McLaren A, Chandler P (1982) Evidence for two male antigens in mice. Immunogenetics 15:609–614

    Google Scholar 

  • Singh L, Jones KW (1982) Sex reversal in the mouse (Mus musculus) is caused by a recurrent nonreciprocal crossover involving the X and an aberrant Y chromosome. Cell 28:205–216

    Google Scholar 

  • Soller M, Padeh B, Wysoki M, Ayalon N (1969) Cytogenetics of Saanen goats showing abnormal development of the reproductive tract associated with the dominant gene for polledness. Cytogenetics 8:51–62

    Google Scholar 

  • Tung PS, Gore-Langton RE, Fritz IB (1982) An objective sperm cytotoxicity assay for male-specific antisera based on ATP levels of unlysed cells: application to assay of H-Y antigen. J Reprod Immunol 4:315–324

    Google Scholar 

  • Wachtel SS (1979) Primary sex determination. H-Y antigen and the development of the mammalian testis. Arthritis Rheum 22:1200–1210

    Google Scholar 

  • Wachtel SS, Ohno S (1979) The immunogenetics of sexual development. Prog Med Genet 3:109–142

    Google Scholar 

  • Wachtel SS, Koo GC, Breg WR, Elias S, Boyse EA, Miller OJ (1975) Expression of H-Y antigen in human males with two Y chromosomes. N Engl J Med 293:1070–1072

    Google Scholar 

  • Wachtel SS, Koo GC, Breg WR, Thaler TH, Dillard GM, Rosenthal IM, Dosik H, Gerald RS, Saenger P, Nao M, Lieber E, Miller OJ (1976a) Serological detection of a Y linked gene in XX males and XX true hermaphrodites. N Engl J Med 295:750–754

    Google Scholar 

  • Wachtel SS, Koo GC, Ohno S, Gropp A, Dev VG, Tantravahi R, Miller DA, Miller OJ (1976b) H-Y antigen and the origin in XY female wood lemmings (Myopus schisticolor). Nature 264:638–639

    Google Scholar 

  • Wachtel SS, Basrur P, Koo GC (1978) Recessive male-determining genes. Cell 15:279–281

    Google Scholar 

  • Wachtel SS, Koo GC, de la Chapelle A, Kallio H, Heyman JM, Miller O (1980a) H-Y antigen in 46,XY gonadal dysgenesis. Hum Genet 54:25–30

    Google Scholar 

  • Wachtel SS, Koo GC, Breg WR, Genel M (1980b) H-Y antigen in X,i(Xq) gonadal dysgenesis: Evidence of X-linked genes in testicular differentiation. Hum Genet 58:183–187

    Google Scholar 

  • Welshons WJ, Russell LB (1959) The Y chromosome as the bearer of male determining factors in the mouse. Proc Natl Acad Sci USA 45:560–566

    Google Scholar 

  • Wiberg U, Mayerová A, Müller U, Fredga K, Wolf U (1982) X-linked genes of the H-Y antigen system in the wood lemming (Myopus schisticolor). Hum Genet 60:163–166

    Google Scholar 

  • Winters SJ, Wachtel SS, White BJ, Koo GC, Javadpour N, Loriaux DL, Sherins RJ (1979) H-Y antigen mosaicism in the gonad of a 46,XX true hermaphrodite. N Engl J Med 300:745–749

    Google Scholar 

  • Wolf U (1979) XY gonadal dysgenesis and the H-Y antigen. Hum Genet 47:269–277

    Google Scholar 

  • Wolf U (1981) Genetics of primary gonadal differentiation. In: Frajese G, Hafez ESE, Conti C, Fabbrini A (eds) Oligozoospermia: Recent progress in andrology. Raven Press, New York

    Google Scholar 

  • Wolf U, Zenzes MT (1979) Gonaden Differenzierung und H-Y-Antigen. Verh Anat Ges 73:374–384

    Google Scholar 

  • Wolf U, Fraccaro M, Mayerová A, Hecht T, Zuffardi O, Hameister H (1980a) Turner syndrome patients are H-Y positive. Hum Genet 54:315–318

    Google Scholar 

  • Wolf U, Fraccaro M, Mayerová A, Hecht T, Moraschio P, Hameister H (1980b) A gene controlling H-Y antigen on the X chromosome. Tentative assignment by deletion mapping to Xp 223. Hum Genet 54:149–154

    Google Scholar 

  • Wolman SR, McMorrow LE, Roy S, Koo GC, Wachtel SS, David R (1980) Aberrant testicular differentiation in 46,XY gonadal dysgenesis: morphology, endocrinology, serology. Hum Genet 55:321–325

    Google Scholar 

  • Yamada K, Isurgi K (1981) H-Y antigen studies in thirty patients with abnormal gonadal differentiation: correlations among sex chromosome complement, H-Y antigen, and gonadal type. Jinrui Idengaku Zasshi 26:227–235

    Google Scholar 

  • Zenzes MT (1979) Studies on the function of H-Y antigen in primary gonadal differentiation. J Cell Biol 83:397

    Google Scholar 

  • Zenzes MT (1980) Studies on the expression of H-Y antigen after in vitro sex-reversal of gonads of non-mammalian vertebrates. Clin Genet 17:95–96

    Google Scholar 

  • Zenzes MT, Wolf U, Günther E, Engel W (1978a) Studies on the function of H-Y antigen: dissociation and reorganization experiments in rat gonadal tissue. Cytogenet Cell Genet 20:365–372

    Google Scholar 

  • Zenzes MT, Wolf U, Engel W (1978b) Organization in vitro of ovarian cells into testicular structures. Hum Genet 44:333–338

    Google Scholar 

  • Zenzes MT, Müller U, Aschmoneit I, Wolf U (1978c) Studies on H-Y antigen in different fractions of the testis during pubescence. Immature germ cells are H-Y antigen negative. Hum Genet 45:297–303

    Google Scholar 

  • Zenzes MT, Urban E, Wolf U (1980) Mammalian cross-reactive antigen induces sex-reversal in vitro in the avian testis. Differentiation 17:121–126

    Google Scholar 

  • Zuffardi O, Maraschio P, LoCurto F, Müller U, Giarola A, Perotti L (1982) The role of Yp in sex determination: new evidence from X/Y translocations. Am J Med Genet 12:175–184

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Zoology, University of Toronto, M5S 1A1, Toronto, Ontario, Canada

    Maria Teresa Zenzes & T. Edward Reed

  2. Department of Anthropology, University of Toronto, M5S 1A1, Toronto, Ontario, Canada

    T. Edward Reed

Authors
  1. Maria Teresa Zenzes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Edward Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zenzes, M.T., Edward Reed, T. Variability in serologically detected male antigen titer and some resulting problems: A critical review. Hum Genet 66, 103–109 (1984). https://doi.org/10.1007/BF00286583

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00286583

Keywords

Search

Navigation