SEX DETERMINATION IN HUMAN

K.K.Gupta, Drosophila Genetic Lab,Dept.of Zoology, VBU,Hazaribag

In Early days the Human a sex was determined by the sex chromosomes that randomly fuses

during Zygote formation . Consequently, Zygote with XX becomes female and that with XY

becomes male. This is normal primary sex condition. But the secondary sex that is development

of sex specific secondary character was doubtful simply on the presence of the only sex

chromosome. The exact mechanisms was explored in the coming days which deals that the sex

is determined by gene expression being located on the sex chromosomes as well as autosomes .

In this regards, primary sex determination deals with the determination of gonads and secondary

sex determination by the development of sex specific accessory sex organs.

The sex determination in human is thus chromosomal and their gene expression. Initial after

fertilization, the sex of embryo is characterized by their chromosomal constituents 44+XX –

Female ; 44+XY male .Unlike Drosophila, the zygotic sex is determined by the presence or

absence of Y chromosomes i.e Presence of Y –Male and absence of Y is female. And thus

maleness is due to dominant Y effect. Both X & Y has similar telomeric ends

.

This is related to presence of SRY gene on Y chromosomes which produces TDF ( Testes

determining factor (TDF) . TDF induces medulla of the embryonic gonads to develop into testes.

Further testosterone secreted by testes at puberty promotes secondary sexual characters

development .(Fig-2.). If there is no testosterone then, only cortex is induced to develops into

female.

As evidenced in genotype of turner syndrome

where Y is absent become female and an

individual with XXY becomes Klinfelters male.

The presence of Y directs the primordial bipotents

gonad to develop in to testis. Initially, the

testosterone secretion influences the development

of secondary sexual characters

Fig. Inheritance of sex chromosomes in Sex determination

Level of Sex determination

There are two levesl of sex determination

A. Primary sex determination

B. Secondary sex determination

Primary sex deremination concerns the determination of gonads i.e Testes in male and ovary in

female which acts as both gamete ( sperm in male & ova in female ) and harmone ( testerone

in male and estrogen in female) producing organs and sex . Thus it is composite endocrine

gland)

Secondary sex determinate is concer with the development of accessory sex organs and

secondary sexual characters in respective sex.

GENETIC BASIS of SEX DETERMINATION

Several research have explored the outcome of sex dertemination has genetic basis and many genes

expression are involved in cascade manner. The embryonic rudiment organ is specific except gonad

which is bipotent. This rudiment is mesodermal and appears in human at 4th week of gestation and

remain indifferent up to 7th week. During this stages the epithelium of genital ridges proliferate in to

loose connective mesnchymal tissues. This forms sex chords which surrounds the germ cells .In both

sexes ,the sex chords are connected to the epithelium. In XY embryo these chords proliferate up to 8th

week and forms rete testes chords .Tunica albuginea also develops. It is only at puberty, the

seminiferous tubules develops and and sperms are produced. In XX embryo the sex chords stops

proliferating after 6th week and restrict to definite no. of germ cells . These germ cells develops in to

primary follicle and stops further development till puberty.

Location Gene Function

Y-linked Gene

SRY [Sex reversal Y linked gene]

TDF

X linked gene

tfm [testicular feminizing gene) and DSX ( ovary determining gene )

receptor for testosterone

Autosomes SF1 Steroidogenic Factor , WNT4 , WT1 SOX9

Promote development of bipoten gonad from genital ridge during development .In male promote anti-mullerian harmone secretion from Sertoli cells of seminiferous tubule which regress mullerian duct in male testosterone from leydig cells which promote wollffian duct

There are two sets of gene

A. Sex linked for sex dermination &

B. Autosomal linked genes for sex determination

SEX LINKED GENES FOR SEX DETERMINATION

SRY Gene –It is holoandous gene which is testes determining gene residing on the short arm of Y

chromosomes . Individual born with only short arm in Y chromosomes become male and those only long

arms bearing Y becomes female. Analysis of DNA reflects that This gene is 35000 base pairs and located

near tip of Y and encode a 223 amino acids containing peptide ( Sinclair et al. 1990). This peptide is a

transcription factor as it has DNA binding box called HMG ( High mobility group) which is common oin

many transcription factor and non histone chromatin protein which induces bending of DNA at 70-80

degree once bind with their ligands. In this case it is the region of promoter of AMH gene . This gene

was called SRY which encodes TDF . SRY binding sites is also located in the Promoter of two other gene

i.e AMH and P40 aromatase also which are involved in the biosynthesis of steroid & secondary sex

determination. A polymerase reaction followed by gel electrophoresis of this gene status in the male,

female and transgenic female with SRY insert (XX male) revealed the presence of similar banding

pattern Fig 2A . Experiments conducted also reveals that if SRY gene is translocated on the X

chromosomes of female , then sex gets reverse i.e become XX male (Sex reversal Y linked genes).

similarly if SRY is deleted from the Y chromosomes , the individual will be transformed in to female. i.e

XY female. (fig. 2B)

Fig -2A &B: Experimental Evidence of SRY gene in male determination

Thus, SRY is sex reversal Y linked gene. Mechanisms illustrate that the The X chromosomes has tfm gene

i.e testicular feminizing gene which expresses a protein which act as testosterone receptor protein. The

receptor and testosterone interaction produce a signal for the differentiation of male . In contrast there

is no signal for sex determination. (fig 3).

Fig 3.Role of SRY gene

A. Dax gene –It is hologyny gene essential for ovary development (Xp21).Two copes of the gene is

needed to differentiate bipotent gonad to proceed for ovary development . In male if Dax becomes

duplicated then a XY becomes female The sex is reverse due to the fact that such zygote gonoidal

dygenesisis takes place . moreover the gomnoad is able to produce aMH and testerone so the

phenotype is female. The DAX gene encodes memer of nuclear membrane receoptor family wich are

expressed in the genital riges during embryogenesis.

AUTOSOMAL GENES IN SEX DETRERMINATION

SOX 9 SRY gene alone can’t induce tesestis formation. It actas repressor and activator for many

autosomal linked gene for eg SOX9 in human . It also act as transcription factor containing an

HMG box . a individual lacking a functional copy suffers from Campomelic Dysplasia ( a

disease with numerous skeletal and organ system leading to death.)It is expressed in male as is

activated by Sry .

SF 1: ( A streiodogenic factor 1). It is also activated by SRY product in male and is invoved in

the several other genes that are encoding enzymes of the testosterone pathway in the leydig

cells.and AMH in the sertoli cells.

Wnt 4a :-A potential ovary determing gene on autosomes.It is expressed in cells of indifferetiated

genital ridges in the XX Individuals .

The probable roles of autosomal linked genes in sex determination are shown below.

Thus, the sex determination In human is completely genetic in which sex determining genes are located

on Y chromosomes, X and autosomes as mentioned above