MSC.BILIGY

1. Human development and sex
determination
PINSET ISLAABAD

2. Introduction
• Zygote is formed as a result of fusion of sperm
(male gamete) and oocyte (female gamete)
• Gametes are produces in gonads
• Gonads are paired organs with associated ducts
and accessory glands
• The fertilization of the male and female gamete
lead to the formation of zygote

3. Human Life cycle

4. Fertilization
• Fertilization means the
sperm joins the egg,
creating the zygote,
which is the first cell of
the new individual
person.
• 23 chromosomes from
sperm plus 23 from the
egg restores the total of
46 chromosomes.
• And, the new
individual is now
either 46,XX (female)
or 46,XY (male)

5. Overview of the male reproductive system

6. Features of male reproductive system
• Testes form in the abdomen during embryonic
development but later descend into Scrotum- sac keep
testes external to body
• Septum divides scrotum into two sacs
• Dartos helps maintain position and internal temperature
• Well vascularized (pudendal,cremasteric branch of
inferior epigastric artery)
• Testes descend into scrotum through inguinal canals
during development
• Duct systems which transport the sperms out of body
• Three sets of glands which secrete fluids to keep sperms
viable and motile
• The penis which is the organ of sexual intercourse

7. Structure and function of the testis
(plural: testes)
• Divided into lobules
• Seminiferous tubules are
tightly packed within
them and sperms are
produced
• Cells within tubules:
▫ Spermatogenic cells divide
via spermatogenesis or
meiosis to produce sperm
▫ Sertoli cells regulate sprem
formation
• Leydig (interstitial) cells
secrete testosterone

8. Sperm
• Once produced sperms
moves from the
seminiferous tubules
into the epididymis
where sperms are
stored
• Sperm formation takes
8-10 weeks (but 300M
are formed every day)
• Adapted for
“swimming” to an
oocyte

9. Transport of sperm from the testis
• Lumen of seminiferous tubule
• Rete testis
• Efferent ducts
• Ductus epididymis
• Ductus deferens
• Ejaculatory ducts
• Urethra
• During the transport of the sperm there are different
secretions which are added
1. Seminal vesicles contribute fructose as an energy source for
sperm
2. Prostaglandins locally acting chemical messengers that
stimulate contraction of female reproductive system for
the assistance in movement of sperm
3. Bulbourethral glands which are present for the lubrication
of the glands during intercourse

10. Accessory glands in males
• Seminal vesicles-alkalinity,
sugar,
coagulants
• Prostate- citric acid,
enzymes; PSA (breaks
down clot)
• Bulbourethral glands-neutralize
acidity of
urethra
• Semen contains these
secretions and sperms

11. Spermatogenesis

12. Overview of the female reproductive system

13. Female reproductive system
• Female gonads are a pair of oval shaped ovaries
about 3cm long located in the abdomen
• Ovary contains many follicles consisting of a
developing egg surrounded by an outer layer of
follicle cells
• Developing egg is a primary oocyte and begins
meiosis in the third month of female prenatal
development
• At birth the female carries a lifetime supply of
developing oocytes each of which is in the first stage
of the meiosis development

14. • The first developing egg called as a secondary
oocyte is released from a follicle at puberty by
ovulation and over a females reproductive
lifetime about 400-500 gametes will be
produced
• The ovulated cell or the secondary oocyte is
swiped into the oviduct also called as the
fallopian tube
• The oviduct is connected to the uterus which is
7cm long and 5cm wide

15. Histology of the ovary

16. Structure of the uterine (fallopian)
tubes
Ciliated cells
help move
ovum
Fertilization
usually
occurs in
ampulla

17. Features of the uterus
• Muscularity is prominent in
the outer layer called
myometrium
• Perimetrium is part of
peritoneum
• Myometrium- three layers
of smooth muscle
• Endometrium- highly
vascularized; secretory
• This blood rich
endometrium is shed during
menstruation if fertilization
has not taken place
• The lower neck of the uterus
is termed as cervix that
opens into the vagina

18. Human development
• During fertilization a sperm binds to the receptors
on the oocyte and other sperms bring about changes
in the oocyte
• We all begin as a single cell, the zygote, produced by
the fusion of a sperm and oocyte
• Zygote ; Fertilized egg that develops into a new
individual
• Zygote travels via ciliary movements into uterus
body in 3-4 days
• Cell divisions occur and gives result into a blastocyst

19. • Blastocyst is 100 celled
• Consist of internal cavity and a cell lining called
troposphere
• The cells of the endometrium enlarge and
prepare for the attachment of the embryo
• The trophoblast attaches to the endometrium
and releases the enzymes which digests some
endometrial cells and provide space for the
attachment of embryo

20. • 12 days after fertilization the two layered structure is formed
over the embryo
• This structure with a trophoblast covered with two layers is
called as chorion
• Once settled chorion releases hCG human chorionic
gonadotropin hormone which nourishes the endometrial
lining and prevents the cells of endometrium from
degeneration
• This also releases other hormones necessary for the
establishment of pregnancy
• As chorion develops it makes finger like projections which
gets vascularized and filled with maternal blood
• The capillaries of the developing embryo also runs in the same
villi separated via single sheath of cells from the maternal
blood
• The villi then eventually forms the placenta
• A disc shaped structure which nourishes the embryo and
helps providing a suitable environment or the development
and growth of embryo

22. • Membranes which connect embryo to the
placenta forms the umbilical cord
• This contains 2 umbilical arteries and an
umbilical vein as an extension to the embryonic
circulatory system

23. Stages of development
• The development of human fetus is divided into
3 trimesters
• First trimester
• Second trimester
• Third trimester

24. 1st trimester
• Organ formation
• Three tissue layers form starting from first week and
at the end of third week the organ systems begin to
take shape
• by 4th week the body is 5mm long and composed of
paired segments of body
• In 5th week the embryo dramatically increase in size
of about 3cm long. Most of the organ systems like
heart are formed
• Limb buds develop into complete arms and legs with
fingers and toes
• Head is larger than other body due to rapid
development of the nervous system

25. • After 7 weeks the embryo is called as a fetus
• Though the sex of the fetus is determined at the
time of fertilization but the physical appearance
of sex is not strict until start of the 9th week
• After 9th week a set of genes is activated which
initiates the sexual development
• Ultrasound scans can reveal the external sex
organs by 12th to 13th week
• At the end of first trimester the fetus is 9cm long
• It weighs about 15g
• All the major organ systems are formed and are
functional to their full extent

26. 2nd trimester
• Major changes include the increase in the size
and maturation of the respiratory system
• Bony parts of skeleton begin to form
• Heartbeat becomes notable with aid of a
stethoscope
• Fetal movements become notable
• At the end of 2nd trimester the fetus weighs 700g
and is 30-40cm in length
• A well formed face arms and legs with finger
nails and toe nails are prominenet

27. 3rd trimester
• Fetus grows rapidly
• Respiratory and circulatory system grow and
prepare to get functional for air breathing
• Maternal nutrition in this period accounts for the
skeletal system development and nervous
development
• Fetus doubles in size in the last two months
• The last month accounts for the immune system
development as maternal antibodies pass into fetus
these antibodies are utilized to be safe from the
diseases until baby’s immune system develops
shortly after birth

28. Birth is hormonally induced
• Oxytocin induces birth
• It is released from the pituitary and stimulate
the uterine contractions
• These contractions stimulate the birth of the
fetus

29. Teratogens Are a Risk to the
Developing Fetus
• The embryo and fetus are sensitive to chemical
and physical agents that can cause birth defects
• Teratogen
▫ Any physical or chemical agent that brings about
an increase in congenital malformations
▫ Radiation, viruses, medications, alcohol

30. Alcohol is a Teratogen
• Fetal alcohol
syndrome (FAS)
• Alcohol is the most
common teratogenic
problem and leading
cause of preventable
birth defects
▫ There is no “safe”
amount of alcohol
consumption during
pregnancy

32. Other teratogens
• Important: not all have severe effects:
consultation with health care provider critical!
▫ Anticonvulsants
▫ Antipsychotics
▫ Antimicrobials
▫ Anti hypertensives
▫ Anticoagulants
▫ Factors: maternal health; maternal infections
(esp. viruses), radiation exposure

33. Human Sex Ratios
• The proportion of males to females, which
changes throughout the life cycle
• The ratio is close to 1:1 at fertilization
• The ratio of females to males increases as a
population ages
• 105 males for every 100 females at birth
• 1:1 at the age of 20-25
• Accidents are major cause of death of males
worldwide during 15-30 years of age

34. Factors in Sexual Differentiation
• The formation of male and female reproductive
structures depends on:
▫ Gene action
▫ Interactions within the embryo
▫ Interactions with other embryos in the uterus
▫ Interactions with the maternal environment

35. Levels of sex development
• There are 3 levels to sexual development:
1. chromosomal sex: presence or absence of the Y
chromosome
2. gonadal sex (primary sex determination): whether the
gonads develop as testes or ovaries depends on the
presence or absence of the SRY gene, usually found on
the Y chromsome
3. phenotypic sex (secondary sex determination): all of
the internal and external structures develop along
male or female lines depending on which hormones
are secreted by the gonads.
• Phenotypic sex also has a couple of distinct systems: the
internal ducts, and the external genitalia
• Two important times: pre-natal development and
puberty

36. Chromosomal sex determination
• We have 46 chromosomes: 23 pairs, one set
from each parent.
• One pair of chromosomes is the sex
chromosomes, X and Y.
• the other chromosomes just have numbers: 1-22.
• A person with 2 X chromosomes (46,XX) is
female, and a person with an X and a Y (46,XY)
is male.

37. Chromosomal basis of sex
determination
Male or female?

38. SRY Gene
How the Y chromosome determines sex.
The SRY gene, located on the Y chromosome, is the
primary determinant of sexual development.
That is, if a developing embryo has a functional SRY
gene in its cells, it will develop as a male. And, if there
is no functional SRY, the embryo develops as female.
Although the SRY gene is usually on the Y
chromosome, it occasionally gets transferred to the X.
this leads to 46,XX males
Also, sometimes the SRY gene is inactivated by
mutation.
Leading to 46,XY females (Swyer syndrome)
it is also possible to have a partially inactive SRY gene,
leading to ambiguous genitalia

39. • Testosterone
▫ A steroid hormone
produced by the testis
▫ Male sex hormone
• Müllerian inhibiting
hormone (MIH)
▫ Hormone produced by
developing testis that
causes breakdown of
Müllerian (female)
ducts in the embryo

40. Early Gonad Development
• Before 6-7 weeks of
development, the gonad is
indifferent: neither male nor
female.
• It develops from the same
tissue as the kidneys and
adrenal glands.
• Also developing by this time: 2
sets of ducts that will
eventually lead to the outside
world.
▫ Wolffian ducts = male
▫ Mullerian ducts = female

41. Gonad Differentiation
• If SRY is present in the
indifferent gonad at 6
weeks, it gets activated.
This in turn activates
other genes, and the
indifferent gonad is
converted to a testes.
• In the absence of SRY, a
different set of genes is
activated, and the
indifferent gonad
becomes an ovary.
• The germ cells, which
actually become sperm
or eggs, migrate into the
gonad about this time.

42. Development of Phenotypic Sex
• The cells of the newly formed testes start secreting the
hormone testosterone.
▫ Testosterone secretion peaks about week 16, with levels similar
to those found in adult males. After this, the testosterone level
drops to about the same level as female fetuses.
▫ The testes also secrete another hormone: Mullerian inhibiting
substance (MIS) (aka anti-Mullerian hormone, AMH).
• Another important process in the developing male:
during the last trimester of pre-natal life, the testes
migrate (“descend”) from the kidney region into the
scrotum.
▫ Under the control of a third testes hormone: “insulin-like
hormone 3”
• The developing ovary secretes estrogen, which is
important after birth, but estrogen from the mother
completely swamps it out before birth.

43. Internal Ducts
• In the early embryo, two duct
systems form. After the gonad
differentiates into a testis or
ovary, one set of ducts develops
further while the other set
degenerates.
• Testosterone causes the Wolffian
ducts to develop into male
structures: epididymus, vas
deferens, seminal vesicles.
▫ In the absence of testosterone, the
Wolffian ducts disappear (except a
bit becomes the adrenal glands in
both sexes)
• Mullerian inhibiting substance
causes the Mulerian ducts to
disappear.
▫ In the absence of MIS, the
Mullerian ducts develop into
the Fallopian tubes, uterus,
and upper vagina.

44. Another Duct Picture

45. Development of the External Genitalia
• This process is controlled by the
presence or absence of dihydrotestosterone
(DHT).
• Testosterone gets converted into DHT by the
enzyme 5-alpha reductase, which is found in
the testes and the skin.
• Both sexes start out with the same structures,
which develop along different lines under the
influence of testosterone and DHT.
• The default condition in female: in the absence
of DHT, the external genital structures develop
along female lines.
• DHT also causes hair loss: male pattern
baldness. Testosterone is converted to DHT
locally. Rogaine works by blocking 5-alpha
reductase

46. • In the absence of DHT, the External Development
genital swellings form the
labia majora; the genital
folds remain unfused and
form the labia minora; the
genital tubercle forms the
clitoris and the urogenital
sinus forms the lower part
of the vagina.
• With DHT present, the
genital swellings migrate
and become the scrotum;
the urogenital folds enlarge
and enclose the penile
urethra and become the
shaft of the penis; the
genital tubercle becomes
the glans penis; and the
urogenital sinus forms the
prostate gland

47. Androgen Insensitivity
• A mutation in the X-linked androgen receptor
gene (AR) causes XY males to become
phenotypic females
▫ Testosterone is produced, but not testosterone
receptors; cells develop as females
• Androgen insensitivity (CAIS)
▫ An X-linked genetic trait that causes XY
individuals to develop into phenotypic females

48. Mutations can cause Sex Phenotypes to
Change at Puberty
• Pseudohermaphroditism
▫ An autosomal genetic condition that causes XY
individuals to develop the phenotype of females
▫ Caused by mutations in several different genes
▫ Affected individuals have both male and female
structures, but at different times of life
▫ At puberty, females change into males

49. Equalizing the Expression of X
Chromosomes in Males and Females
• Human females have one X chromosome
inactivated in all somatic cells to balance the
expression of X-linked genes in males and
females

50. Dosage Compensation
• Females have two X chromosomes, males have
one; yet the amount of gene product is the same
• Dosage compensation
▫ A mechanism that regulates the expression of sex-linked
gene products

51. Barr Bodies and X Inactivation
• Lyon hypothesis (proposed by Mary Lyon)
▫ Dosage compensation in mammalian females
▫ Random inactivation of one X chromosome in females
equalizes the activity of X-linked genes in males and
females
• Barr body
▫ A densely staining mass in the somatic nuclei of
mammalian females
▫ An inactivated X chromosome, tightly coiled

52. Female Mammals are Actually Mosaics
for X Chromosome Expression
• In females, some cells express the mother’s X
chromosome and some cells express the father’s
X chromosome
▫ Inactivated chromosome can come from either
mother or father
▫ Inactivation occurs early in development
▫ Inactivation is permanent; all descendants of a
particular cell have the same X inactivated
▫ Genetic regulation (Xic) of which chromosome is
inactivated

53. Effects of Random
X-Chromosome Inactivation
• Random X inactivation
can cause twins with
identical genotypes to
have different
phenotypes (also calico
cats!)
Fig. 7-20, p. 171

54. 7.8 Sex-Related Phenotypic Effects
• In sex-influenced and sex-limited inheritance,
the sex of the individual affects:
▫ whether the trait is expressed
▫ the degree to which the trait is expressed
• This is true for autosomal and sex-linked genes
▫ Sex hormone levels modify expression of these
genes, giving rise to altered phenotypic ratios

55. Sex-Influence Traits
• Sex-influenced traits
▫ Traits controlled by autosomal genes that are
usually dominant in one sex but recessive in the
other sex

56. A Sex-Influenced Trait
• Pattern baldness
▫ Acts like an autosomal dominant trait in males and an
autosomal recessive trait in females
The difference is
testosterone

57. Sex-Limited Traits
• Genes that produce a phenotype in only one sex
▫ Example: Precocious puberty in heterozygous males but
not in heterozygous females
• Traits expressed only in females because males die
before birth
▫ Example: Male-lethal X-linked dominant traits
• Traits expressed only in males
▫ Example: Duchenne muscular dystrophy (X-linked
recessive); males do not have offspring and don’t pass their
X onto daughters
▫ Result: very rare in females

58. Imprinting
• One copy of a gene is inactivated, depending on
whether it comes from the father or the mother
▫ Example: NOEY2 gene; paternal copy is expressed
in normal breast and ovarian cells
• Imprinting
▫ A phenomenon in which expression of a gene
depends on whether it is inherited from the
mother or the father
 Chemical modification of DNA (more common)
 Uniparental disomy (rare)

59. Thanks 