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What is Sex
1.
2.
3. What is sex?
Sex is the state of being either
male or female.
We can expand our look and define
sex by looking at three levels:
• Chromosomal sex.
• Gonadal sex.
• Phenotypic (anatomical) sex.
In the developing fetus, the genetic or
chromosomal sex is determined at the time of
fertilization. However, the presence of an intact Y
chromosome is essential for male regardless of the
number of X chromosomes present, and absence
of a functioning Y chromosome results in female.
4. Sex Determination
The process that leads to the
development of gonads is called sex
determination.
Simple statement!
Sex determination process contains:
Formation of chromosomal sex
at fertilization(undifferentiated
stage).
Selection of the male or
female pathway of
gonadal differentiation
(gonadal differentiation).
Sexual differentiation of the internal and
external genitalia.
01 02
03
MALE OR
FEMALE?
5.
6. IMAGINE! in man the default developmental
pathway is woman! Although the sex chromosomes are
present once the Zygote is created, differentiation into
male or female does not commence until approximately 6
weeks. Up to this point the embryonic ambipotent gonad
is still undifferentiated and fetuses of both sexes have
two sets of internal ducts: the Müllerian ducts and the
Wolffian ducts. THEN WHAT?
From 6 weeks onwards, the embryo develops
into a female unless the ‘testis-determining
factor’— Y-linked gene (the SRY gene) —initiates
a sequence of events that prompt the
undifferentiated gonads to develop into testes.
The SRY gene is located on chromosome Yp
close to the pseudoautosomal region.
Expression of SRY triggers a series of events
that involves inhibition of an upstream
repressor of SOX9 (a major autosomal gene),
allowing the latter to be upregulated.
7. In male: Presence of SRY and expression of SOX9 causes the
nonspecific gonad to develop as a testis. Once testis
development is initiated by action of the SRY gene, cells in the
testis secrete two hormones: androgens and anti-Mullerian
hormone (AMH). androgens, secreted by Leydig cells, are
responsible for the development of the Wolffian ducts. and that
AMH, secreted by Sertoli cells, drives the regression of the
Müllerian ducts.
In female: In the absence of testes and, therefore, of
androgen and AMH action, Wolffian ducts regress, and with the
helping of β-catenin (CTNNB1) Müllerian ducts develop and
follow the female pathway. There are several genes seem to
have both pro-ovarian and anti-testicular activities from early
embryonic life such as: RSPO1, WNT4, FOXL2.
8.
9. Is it all about Y chromosome?
In addition to the Y chromosome, a multitude
of other genes influence sex determination and
are able to cause male to female sex-reversal.
These genes are located in autosomal
chromosomes or even in the X chromosome.
Remember: During
normal meiosis in
the male, crossover
occurs between
the tip of the Y
chromosome and
the tip of the X
chromosome.
10. Occasionally, the
crossover occurs on
an abnormal side,
causing Y-linked
gene to lie on an X
chromosome
instead of on the Y
chromosome. An
offspring receiving
this X chromosome
will be an XX male,
and an offspring
receiving the Y
chromosome will be
an XY female.
11. DSD
Disorders of sex development (DSD)
are congenital medical conditions in
which there is no correlation between
the chromosomal, gonadal, and
phenotypic characteristics.
12. DSD can be divided based
on many considerations :
Karyotype,
Physical Appearance,
Pathologically.
13. The role of genes is crucial, so the right
gene and its consequences must be
released at the :
QUANTITY
01 02 03
PLACE TIME
IS IT GENE?
18. ▪ Nussbaum, R., McInnes, R.,
Willard, H. and Hamosh, A.,
2016. Thompson &
Thompson Genetics In
Medicine. Philadelphia:
Elsevier, pp.87-102.
▪ Jorde, L., 2016. Medical
Genetics. 5th ed.
Philadelphia: Elsevier,
p.116.
▪ Connor, J., Tobias, E. and
Ferguson-Smith, M., 2016.
Essential Medical Genetics.
6th ed. Chichester: Wiley-
Blackwell, p.83.
▪ Disorders of Sex
Development, Jameson J,
Fauci AS, Kasper DL,
Hauser SL, Longo DL,
Loscalzo J. Harrison's
Principles of Internal
Medicine, 20e; 2018.
▪ Karger.com. 2020. [online]
Available at:
<https://www.karger.com
/Article/FullText/452637>.