This document discusses sex determination and differentiation. It begins by explaining that sex is determined by X and Y chromosomes, with females having two X chromosomes and males having one X and one Y chromosome. It then describes the process of sex differentiation in males and females both internally and externally. It discusses factors involved like Müllerian inhibiting substance and testosterone. It outlines several sex chromosomal abnormalities including Turner syndrome, Klinefelter syndrome, and various types of pseudohermaphroditism. The document aims to explain the physiology of sex determination and differentiation and its abnormalities.

1. SEX DIFFERENTIATION AND
DEVELOPMENT
PY9.1: Describe and discuss sex determination; sex
differentiation and their abnormities and outline psychiatry
and practical implication of sex determination.

2.  The student will be able to: (MUST KNOW)
 Understand the physiology of sex determination and differentiation.
 Describe the mechanism of sex differentiation and development in males and females.
 Outline the regulation of sex differentiation.
 List the abnormalities of sex differentiation and understand the physiological basis of
their causation.
 Name the common genotypic and phenotypic features of Turner syndrome and
Klinefelter syndrome.
 Name the common developmental anomalies and differentiate between male and
female pseudohermaphroditism.
 Apply the knowledge of sex determination and differentiation in understanding the
physiology of reproductive dysfunctions

3. INTRODUCT
ION
 Reproduction serves a primary goal of the
nature for preservation and perpetuation
of the species.
 The creation of two sexually complete
and different individuals in same species,
known as sexual dimorphism, is the
central scheme of the nature to achieve its
principal purpose of continuation of species
through reproduction.
 The complete sexual dimorphism is
obtained through the attainment of
puberty. The sexually matured adults then
reproduce to maintain their progeny.

4. Sex Determination
 Normal Chromosomal Pattern
 In a normal human being, there are 46 (23 pairs) chromosomes:
 22 pairs are autosomes, and one pair is sex chromosome
In Males
 The pattern is 22 pairs of autosomes, and one X and one Y chromosomes (44 XY).
In Females
 The pattern is 22 pairs of autosomes and two X chromosomes (44 XX).

5. Fig: Chromosomal pattern in males
(44 XY) and females (44 XX).

6. Gender is determined by the genetic inheritance of two chromosomes, called sex chromosomes.
The two sex chromosomes are the X chromosome, the larger one, and the Y chromosome, the
smaller one.
1. Females possess two X chromosomes and males have one X and one Y chromosome. Thus,
ovum always contributes only one X chromosome, whereas half of the sperms contribute X
and another half Y.
2. Therefore, union of sperm and ovum (fertilization) usually results in half XX and half XY.
Hence, ideally, births of male and female children should have been in equal proportion.
3. However, generally, the male births are slightly more than the female births.

7. Sex determination is usually done by karyotyping, a technique used for determining sex chromosome
composition by employing tissue culture visualization of all chromosomes. The differences in shape and
size of chromosomes in males and females help in concrete determination of sex.
Figs. : Chromosomal pattern (karyotyping) in (A) Males
and (B) Females. Note that X chromosome is larger than Y chromosome.
KARYOTYPING

8.  Figs:A to C: Differentiation
of the male and female
internal genitalia. (A)
Indifferent stage; (B) Male
internal genitalia; (C) Female
internal genitalia. Note that,
in male, mullerian duct
degenerates and in female,
Wolffian duct degenerates.
A
B

9. Figs.A to E: Differentiation of
the male and female external
genitalia. (A) Indifferent stage;
(B) Male genitalia (7th to 8th
week); (C) Male genitalia (at
about 12th week); (D) Female
genitalia (7th to 8th week);
(E) Female genitalia (at about
12th week).
DIFFERENTIATION OF THE MALE AND FEMALE EXTERNAL GENITALIA
A
B C D E

13.  Also known as anti-müllerian hormone or müllerian regression factor, MIS is a polypeptide
hormone containing 536 amino acids secreted by the Sertoli cells of testis. It belongs to the
TGF-β superfamily of growth factors that include activin and inhibin.
 In males, though the secretion of MIS starts at 8–10 weeks of gestation, the level in plasma
reaches its peak, i.e., about 50 ng/mL at 1–2 years of age.
 The concentration then declines gradually to a low-level during puberty and a lower
concentration of about 2–5 ng/mL is maintained through rest of life.
 In females, granulosa cells of some ovarian follicles start secreting MIS at a low rate
during puberty and continue in a similar fashion thereafter.
 Therefore, the adult female plasma level of MIS is same as that of males.
 However, the exact role of MIS in adults, especially in females, is not known.

14. 1. During early embryonic life, MIS inhibits development of female gonads by
promoting regression of Mullerian duct. Therefore, it helps in male gonadal
development.
2. Later during foetal life in males, it helps in testicular descent.
3. In both sexes, it helps in maturation of germ cells.

16. Chromosomal Abnormalities
 Turner Syndrome
 This is otherwise known as gonadal or ovarian dysgenesis.
 It is characterized by diminished sexual development, dwarfism, and webbing of the neck in
patients with no gonadal tissue or rudimentary gonads.
 The chromosomal pattern of sex chromosomes is XO, which means there are 44 autosomes
and one X chromosomes (total 45 chromosomes).
 It results from nondisjunction of one of the X chromosomes during oogenesis.
 Usually, it presents with primary amenorrhea. No sexual maturation occurs at puberty.

18.  Fig. Turner syndrome. Note the small breast,
webbed neck, and short stature and coarctation
of aorta in a female with this syndrome

19. Klinefelter Syndrome
This is the most common sex chromosome abnormality. The syndrome is otherwise called seminiferous
tubule dysgenesis.
1. Typically, it is characterized by the presence of feminine features in an apparent male with small
testes.
2. The patient is genetically female, but the presence of an extra Y chromosome causes development of
the testis. Therefore, the karyotype is 47 XXY (44 autosomes + XX sex chromosomes + one extra Y
chromosome).
3. They have male genitalia and at puberty male characteristics develop due to adequate testosterone
4. But, seminiferous tubules are not properly developed and therefore, infertility results.
5. Thus, the syndrome usually presents with primary hypogonadism and infertility in male. Mental
retardation is common.

21.  Fig: Klinefelter syndrome. Note the
gynecomastia and small testis and small penis
in a male with this syndrome.

22.  Pseudohermaphroditisms
Pseudohermaphrodite is an individual with genetic constitution and gonad of one
sex, but the external genitalia of the other sex. There are male and female
pseudohermaphrodites. In these conditions, the patients have normal gonadal
development in accordance with their chromosomal sex, but afterward, they develop
heterosexual characteristics due to opposite hormonal excess.

23.  Male external genital development occurs in genetic females exposed to androgen
during the 8th to the 13th week of gestation.
 Source of androgen is usually congenital virilizing adrenal hyperplasia of fetus or
virilizing ovarian tumor of the mother.
 Sometimes it may be iatrogenically induced following treatment of mother with
androgens or pregestational drugs.
 In a typical female pseudohermaphrodite, the individual possesses ovaries,
oviducts, but there is varying degrees of masculine differentiation of external
genitalia.
 The chromosomal sex is female.

24.  Development of female external genitalia in a genetic male is called male
pseudohermaphroditism.
 It is usually due to defective testicular development.
 As MIS secreted from the testis during early embryonic life prevents the development of
female gonads, in defective testicular development, the internal genitalia are also of female
pattern.
 Male pseudohermaphroditism could also be due to androgen resistance that usually occurs in
deficiency of 5a-reductase, the enzyme that forms dehydroepiandrosterone or due to defects in
androgen receptors.
 In complete androgen resistance syndrome (testicular feminizing syndrome), MIS is secreted
as testes are normal; therefore, vagina ends blindly due to the absence of internal genitalia.

25. Congenital 17a-hydroxylase deficiency causes
male pseudohermaphroditism. This also occurs in
congenital adrenal hyperplasia in which enzyme
defects block the formation of pregnenolone