This document summarizes a seminar presentation on the H-Y antigen in mammals. It discusses that the H-Y antigen, encoded by the SMCY gene on the Y chromosome, is responsible for testes differentiation in mammals. It is a cell surface antigen that binds to receptors on cells and triggers their differentiation into testicular structures through a cascade involving hCG and testosterone. Evidence for its role includes experiments showing dissociated ovarian cells can reorganize into testes when exposed to H-Y antigen. Disorders related to H-Y antigen include secondary recurrent miscarriage which may have an immunological basis, as well as graft-vs-host disease when transplanting between sex mismatched individuals. The conclusion re

1. A Seminar
on
“H-YAntigen in Mammals”
Submitted to:-
Department of Zoology
Kurukshetra university
Kurukshetra
Submitted by:-
Ajay Kumar
M.Sc. Zoology (P)
Roll no. 56

2. Contents:-
• Introduction
• H-Y Antigen
• Mouse Y chromosome
• Human Y chromosome
• H-Y Antigen cellular attachment sites
• Role in Testes Differentiation
• Evidences in support of role in Testes differentiation
• Types of H-Y Antigen
• Serological Detectable H-Y Antigens
• T cell mediated H-Y Antigens
• H-Y Antigen and Disorders
• H-Y Antigen relation to Male Homosexuality
• Conclusion
• References

3. Introduction
• Sex determination describes the genetic and
environmental processes that influence sex
differentiation.
• Sex differentiation includes Testicular and
Ovarian development.
• Most common XX/XY in placental Mammals
and in Birds ZZ/ZW.
• Environmental sex determination occur in fishes
and reptiles.
• H-Y Antigen is responsible for differentiation of
gonads into testes.

4. H-Y Antigen
Firstly, discovered by Eichwald and Silmser (1955).
They found skin graft rejection in isogenic mice strain.
Male tissue specific antigen present on cell surface.
It is encoded by the gene Smcy/SMCY present on Y chromosome.
It encodes for a epitope that triggers a specific T-cell response in vitro for the
rejection of male graft by the female graft.
Snell gave name H-Y them for histocompatibility.
It can be detected at 8-cell stage embryo.

5. Mouse Y chromosome
• Cytotoxic lysis found H-Y Antigen in
XXSex reversal Infertile male mice
• Two types of mice strain:
Sxra - H Y antigen positive
Sxrb - H Y antigen negative
• Deleted region >900kb of short arm Y
chromosome in Sxrb encode for Smcy
• Smcy and Sdma gene cause expression
of antigen
• Spy responsible for the spermatogonial
proliferation. Fig. Sex reversed region of short arm
of Y Chromosome

6. Human Y Chromosome
• The genetic map of
human Y
chromosome shows
location of gene.
• In human, the SMCY
gene lies on the long
arm of the Y
chromosome.
• This lies within the
AZF region.
Fig.2. Location of SMCY gene on Y chromosome

7. H-Y antigen cellular attachment sites
It is cell surface antigen bind to the plasma membrane.
Binding by two ways:-
1. By B2-m-MHC dimer
• It is identical in structure to immunoglobulin dimer
• H-Y antigen bind with dimer of H-2 (mouse) and HLA(Human).
2. By specific receptor
• H-Y antigen are gonad specific in nature
• Their receptor are found in both male and female.

8. Three genes governed testicular
differentiation .
• HY antigen producing
gene on the Y
chromosome
• HY activator gene
on the X chromosome
• HY membrane acceptor
gene on the
autosome or the X
chromosome

9. Role in testis differentiation:-
• Association to membrane activate the specific ligant called
cognin.
• Cognin guide the primitive cells to arrange into tubular
structure.
• H-Y Ag induces the expression of hCG (human chorionic
gonado- tropin) receptor on the male embryonic gonads.
• hCG Stimulate the Leydig cell to secret testosterone that cause
development of secondary accessory organs.

10. Evidence
support role in
testis
differentiation
1. Given by the Zenzes.et.al. (1978).
They reported that new born rat ovarian
cells were dissociated and placed in a
rotation culture with a source of H-Y
antigen reorganized to form the testicular
structure.
2. Muller, also found dissociated ovary
reorganized was not only histologically, but
also functionally by treating wth hCG
hormone.

11. Types of H-Y antigen on the behalf of detection:-

12. H-Y antigen and Disorders:-
Secondary Recurrent Miscarriage (SRM) is defined as occurrence of
three or more miscarriages without a preceding successful birth.
SRMs are more likely to be the result of immunological cause.
This reduced live birth rate and increased risk of obstetric
complication.
In SRM patient, male/female sex ratio shifted toward lower no.

13. Graft vs Host Disease
• In hematopoietic cell transplantation (HCT):for example, grafts from
male donors to female recipients (F to M lead to increased rates of
graft-versus-host disease (GVHD).
• In sex-mismatched transplantation, GVHD is associated with
alloimmunity, which occurs when native donor lymphocytes target
mHAs such as H-Y antigens on normal host tissues in order to
produce a combined humoral and cellular responses leading to
significant morbidity and mortality.

14. H-Y Antigen
related to
Male
homosexuality
• It was reported that men with older brother have a
higher chance of being homosexual.
• For every additional older brother, a man's chance of
being homosexual can rise by up to 33%.
• Maternal response to H-Y antigen causes inhibitory
effect on masculinization of the brain that increases
with every succeeding male birth.
• The Detrimental effects of immunization of female
to H-Y antigen on the reproductive performance of
subsequent male offspring.
• Recent research found that neuroligin NLGN4Y
protein, a Y-chromosome protein important in male
fetal brain development, to be involved in the
fraternal birth order effect.

15. Conclusion:
The H-Y antigen present in the male and absent in the female. The critical
threshold concentration of antigen is required for testicular differentiation.
Testicular differentiation is controlled by genes located on one autosome
and the X and Y chromosome. Under genetic impulse, Sertoli cells secrete
the male specific antigen (HY antigen). The antigen attaches itself to
membrane specific receptors of the primitive gonadal cells with the help of
B2- microglobulin and induces the transformation of the gonadal anlagen
into a functioning testis.
Also the sex reversion mechanism in mammals defined by the H-Y antigen
and the probable reason for the Secondary Recurrent Miscarriage, Graft-
versus-host disease, Male Homosexuality is understood by the H-Y antigen

16. REFERENCES:-
Agulnik, A. I., Mitchell, M. J., Woods, D. R. and Bishop, C. E. (1994). A
mouse Y chromosome gene encoded by a region essential for
spermatogenesis and expression of male specific minor
histocompatibility antigens. Human molecular genetics.3(6):873-878.
Goldberg, E. H., Wiberg.U, Bradley.M and Sharma H. (1988). H-Y
Antigen and sex determination. Royal Society. 322:73-81.
Muller.U. (1996). H-Y Antigens. Hum Genet. 97:701-704.
Muller, U.( 1978). Appearance of HCG receptor after conversion of new
born ovarian cell into testicular structure by H-Y antigen in vitro.
Human genetics.45:203-207.

17. Raina, D., Sharma, G. and Prashar, N. (2016). Secondary recurrent
miscarriage and sex of previous child. Int J Reprod Contracept Obstet
Gynecol.5(5):1621-1624
Golimbu, M. (1984). H-Y Antigen: Genetic control and role in Testicular
differentiation. Urology. 24(2):115-121.
Meck, J. M. (1984). The genetics of the H-Y antigen system and its role in
sex determination. Jhons Hopkins University Press. 27(4):560-580.
Popli, R., Sahaf, B., Nakasone, H and Miklos, D.B. (2014). Clinical impact
of H-Y alloimmunity. Stanford Immunology. 58:249–258.
Wolf, U. (1998). The serologically detected H-Y antigen revisited.
Cytogenet Cell Genet.80:232-235.