Normal and abnormal sexual development ppt

Chapte r 3

Normal and abnormal sexual

development and puberty

Sexual differentiation

Genetic sex

Abnormal development

21 Puberty

21 Common clinical presentations

22 and problems

26

27

OVERVIE W

Sexual differentiation and normal subsequent development are fundamental to the continuation of the human species. In recent

years, our understanding of the control of this process has greatly increased. Following fertilization, the human embryo will

differentiate into a male or female fetus, and subsequent development is genetically controlled. This chapter describes the

processes involved and discusses the subsequent evolution to full maturation.

Sexual differentiation Genetic sex

The means by which the embryo differentiates is con￾trolled by the sex chromosomes. This is known as

fenetic sex. The normal chromosome complement is

46, including 22 autosomes derived from each parent.

An embryo that contains 46 chromosomes and. has

tr.e sex chromosomes XY will develop as a mate. If the

M chromosomes are XX, the embryo will differenti￾Jie into a female. The resulting development of the

gonad will create either a teslis or an ovary. This is

known as gonaclal sex. Subsequent development of

*e internal and external genitalia gives phenotypic

^-. i>r the sex ol appearance. Cerebral differen-

•arion to a male or female orientation is known as

hi the developing embryo with a genetic complement

of 46 XY, it is the presence of the Y chromosome that

determines that the undifferentiated gonadwill become

a testis (Fig. 3.1). Absence of the Y chromosome will

result in the development of an ovary. On the short arm

of the Y chromosome is a region known as the SRI'

gene, which is responsible for the determination of tes￾ticular development as it produces a protein known

as testicular determining factor (TDF). TDF dircc

influences the undifferentiated gonad to become ;

testis. When this process occurs, the testis abt

Miillerian inhibitor.

The imdifferentiated embryo contains b

and Miillerian ducts. The Wolffian du

22 Normal and abnormal sexual development and puberty

Undiflerentiated

gonad

iJTDF

Testis

Un differentiated

gonad

Ovar

1

y

Sertoli

cells

Mullerian

inhibitor

Leydig

cells

Testosterone

5a￾reductase

Wolffian Dihydro￾development testosterone

V

No No

Mullerian testosterone

inhibitor

Mullerian

regression

Vas deferens

Epididymis

Seminal

vesicles

Penis

Scrotum

Figure 3.1 Male differentiation. (TDF. testicular determining

factor.)

potential to develop into the internal organs of the

male, and the Mullerian ducts into the internal organs

of the female. If the testis produces Mullerian inhibitor,

the Miillerian ducts regress.

The testis differentiates into two cell types, Leydig

cells and Sertoli cells. The Sertoli cells are responsible

for the production of Mullerian inhibitor, which leads

to Mullerian regression. The Leydig cells produce

testosterone, which promotes the development of

the Wolffian duct, leading to the development of

vas deferens, the epididymis and the seminal vesicles.

Testosterone by itself does not have a different effect

on the cloaca; in order to exert its androgenic effects,

it needs to be converted by the cloacal cells through

the enzyme 5<*-reductase to dihydrotestosterone. These

androgenic effects lead to the development of the penis

and the scrotum.

The absence of a Y chromosome and the presence

of two X chromosomes mean that Mullerian inhibitor

is not created, and the Mullerian ducts persist in the

female (Fig. 3.2). The absence of testosterone means

that the Wolffian ducts regress, and the failure of andro￾gen to affect the cloaca leads to an external female

phenol ype.

Miillerian Wolffian

development regression

Uterus

Fallopian tubes

Cervix

Vagina

Figure 3.2 Female differertialion. (TOP, testicular determining

factor.)

Abnormal development

Any aberration in development that results in an

unexpected developmental sequence of events may be

mediated in a number of ways.

Chromosome abnormalities

In an embryo that loses one of its sex chromosomes,

the total complement of chromosomes will be reduced

to 45, leaving a fetus viable only where this is 45 XO

(Turner's syndrome). Here, the absence of the second

X chromosome or Y chromosome means there is no

testicular development and therefore the phenotype

is female (Fig. 3.3). The gonad is, however, unable to

complete its development and, although it initially

differentiates to be an ovary, the oogonia are unable

to complete their development and at birth only the

siroma of the ovary is present (streak ovaries). Thus,

in Turner's syndrome, the absence of a functional ovary

means that there is no oestrogen production at puberty,

and secondary sexual characteristics cannot develop.