PERKEMBANGAN JANIN

INTRA-UTERIN
DAN
GANGGUAN YANG MUNGKIN TIMBUL

Rahmatina B. Herman
Bagian Fisiologi
Fakultas Kedokteran Unand
 Introduction
Initial development of placenta and fetal membranes
occurs far more rapidly than development of fetus itself
Until 2-3 weeks after implantation of the blastocyst, the
fetus remains almost microscopic
After 3 weeks of implantation, the length of fetus
increases almost in proportion to age
At 12 weeks: 10 cm; at 20 weeks: 25 cm; at term (40
weeks): 53 cm
The weight of fetus is approximately proportional to the
cube of length the weight increases almost in
proportion to the cube of fetus age
Growth of fetus
 Stages and Events of Human Prenatal Development
STAGE TIME PERIOD PRINCIPAL EVENTS
Fertilized 12-24 hours Secondary oocyte fertilized;
egg following ovulation zygote has 23 pairs of chr
Cleavage 30 hours 3rd day Mitosis increases cell number
Morula 3rd to 4th day Solid ball of cells
Blastocyst 5th day through 2nd Hollowed ball forms trophoblast
week (outside) and inner cell mass,
which implants to form
embryonic disc
Gastrula End of 2nd week Primary germ layers formed
- The embryonic stages extends until the 8th week of prenatal
development: placenta forms, the main internal organ develops,
and the major external body structures appear
- The fetal stage begins at the end of the 8th week - lasts until birth
 Fertilization
Definition: the union of male and female gametes
Can take place during fertile period in each cycle
Normally occurs in ampulla
Thus, both ovum and sperm must be transported
from their site of production to the ampulla
During first 3-4 days following fertilization, zygote
remains within ampulla, because of constriction
between ampulla and remainder oviduct canal
prevents further movement of zygote into uterus
A number mitotic cell divisions of zygote to form morula
during in ampulla
Parents with diploid (46 chr) somatic cells
Mother Father
Meiotic division Meiotic division
of germ cells of germ cells

Haploid Ovum Haploid Sperm

Fertilization

Diploid fertilized Ovum

Mitosis

Offspring of diploid somatic cells

 Ovum with X sex chromosome
Fertilized by
Sperm with Y sc Sperm with X sc

Embryo with XY sc Genetic sex Embryo with XX sc

Sex-determining region No Y chr, so no SRY

of Y chr (SRY) stimulates and no H-Y antigen
Production of H-Y antigen
In plasma membrane of
undifferentiated gonad

H-Y antigen directs Gonadal With no H-Y antigen,

differentiation sex undifferentiated gonads
of gonads into testes develop into ovaries
 Testes secrete hormone and factor
Testosterone Mullerian-inhibiting factor

Converted to
Dihydrotestosterone Degeneration of
(DHT) Mullerian ducts

Transforms Wolfian ducts

Promotes development of into male reproductive tract
undifferentiated external (e.g. epididymis, ductus
genitalia along male lines deferens, ejaculatory duct,
(e.g. penis, scrotum) seminal vesicle)

Phenotype
sex
 Ovaries does not secrete hormone and factor
Absence of testosterone Absence of Mullerian-
inhibiting factor

Degeneration of
Wolfian ducts

Undifferentiated external Mullerian ducts develop

genitalia along female lines Into female reproductive
(e.g. clitoris. labia) tract (e.g. oviducts, uterus)

Phenotype
sex
 Descent of Morula to Uterus
3-4 days after ovulation, progesterone produce is
sufficient to relax oviduct contraction morula
rapidly propelled into uterus by oviductal peristaltic
and ciliary activity
Temporary delay of descending embryo into uterus,
lets enough nutrients accumulate in uterine lumen
to support embryo until implantation can take place
Morula will die, if it arrives prematurely
 Descent of Morula to Uterus
Morula floats freely within uterine cavity for 3-4
days, living on endometrial:
- secretions and continuing to divide
- being prepared for implantation under
influence of luteal-phase progesterone
- storing up glycogen
- becoming richly vascularized
Morula which fails to descend into uterus will lead
to ectopic tubal pregnancy (95% of ectopic
pregnancy)
 Implantation
1 week after ovulation, morula has descended into
uterus and continued to proliferate and differentiate
into blastocyst which capable to implantation
Blastocyst is consisted of 2 parts: inner cell mass
(which become fetus) and trophoblast (outermost
layer of blastocyst)
Trophoblast accomplish implantation, after which
develops into fetal portion of placenta
When blastocyst is ready to implant, its surface
becomes sticky, by the time endometrium is ready to
accept the early embryo
Formation of Placenta and Amniotic Sac
By day 12:
- embryo is completely embedded in decidua
- trophoblastic layer (2 cell layers) thick chorion
Chorion continues to release enzymes and expand
- forms extensive network of cavities within decidua
- erodes decidual capillary walls maternal blood
leaks and fills the cavities
- produces anticoagulant to keep blood clotting
Developing embryo sends out capillaries into
chorionic projections to form placental villi
 ..Formation of Placenta and Amniotic Sac

Each placental villus contains embryonic/ fetal

capillaries surrounded by a thin layer of chorionic
tissue, which separates the embryonic/fetal blood
from maternal blood in intervillus spaces barrier

All exchanges between fetal and maternal

bloodstreams take place across the extremely thin
barrier
 ..Formation of Placenta and Amniotic Sac

Entire system of interlocking maternal (decidual)

and fetal (chorionic) structures makes up the
placenta
By 5 weeks after implantation:
- Placenta is well established and operational
(even though not fully developed)
- Heart of developing embryo is pumping blood
into placental villi as well as to embryonic tissues
 Placenta
Specialized organ of exchange between maternal
and fetal blood
Derived from:
- trophoblastic tissue, and
- decidual tissue
Function: to sustain the growing embryo / fetus
during intrauterine life
 Functions of Placenta
Transport system between maternal blood and fetal
blood:
- Nutrition & O2 and metabolic wastes & CO2
- Drugs, pollutants, cigarette smokes,
chemical agents, microorganisms harmful
(thalidomide, AIDS, drug abuse)
Temporary endocrine organ:
Fetally derived portion has remarkable capacity to
secrete peptide and streoid hormones for
maintaining pregnancy
 Placental Hormones
HORMONES FUNCTION
1. Human chorionic - Following implantation, cells of embryo begin
gonadotropin to secrete hCG
(hCG) - Maintains CL of pregnancy
- Stimulates secretion of testosterone by
developing testes in XY embryo
2. Estrogen - Stimulates growth of myometrium, increasing
uterine strength for parturition
- Helps prepare mammary glands for lactation
3. Progesterone - Suppresses uterine contraction to provide a
quiet environment for fetus
- Promotes formation of cervical mucus plug to
prevent uterine contamination
- Helps prepare mammary glands for lactation
 ..Placental Hormones
HORMONES FUNCTION
4. Human Chorionic - Believed to reduce maternal use of glucose and to
Somatomammo promote breakdown of stored fat so that greater
tropin (hCS) quantities of glucose and free fatty acids may be
similar to GH and shunted to fetus
prolactin - Helps prepare mammary glands for lactation
5. Relaxin - Soften cervix in preparation cervical dilation at
parturition
- Loosens connective tissue between pelvic bones
in preparation for parturition
6. Placental PTHrp - Increases maternal plasma Ca2+ level for use in
(Parathyroid calcifying fetal bones, if necessary promotes
Hormone-related localized dissolution of maternal bones, mobilizing
peptide) Ca2+ stores for use by developing fetus
 Preventing Rejection of Embryo
Theory I:
Trophoblast produce Fas ligand which binds with
Fas, a specialized receptor on surface of approaching
activated maternal cytotoxic T cells (immune cells
that carry out the job of destroying foreign cells)
The binding triggers immune cells that are targeted
to destroy the developing foreigner to undergo
apoptosis, sparing embryo/fetus from immune
rejection
 ..Preventing Rejection of Embryo

Theory II:
Fetal portion of placenta which derived from
trophoblast produce enzyme indoleamine 2,3-
dioxygenase (IDO) which destroy tryptophan (critical
factor in activation of maternal cytotoxic T cells)
Theory III:
In pregnancy production of regulatory T cells is
doubled or tripled which suppress maternal
cytotoxic T cells
Growth and Functional Development of Fetus

Initial development of placenta and fetal membranes

occurs far more rapidly than development of fetus
2-3 weeks after implantation of blastocyst, the fetus
remains almost microscopic in size
But thereafter the length of fetus increases in
proportion to age:
- At 12 weeks : 10 cm
- At 20 weeks : 25 cm
- At 40 weeks (at term) : 53 cm
 Development of Organ Systems
Gross characteristics of different organs:
- Within 1 month after fertilization begun to develop
- During the next 2-3 months, most of details are
established
- Beyond the 4th month: mainly the same as those of the
neonate
Cellular development in each organ is usually far from
complete:
- Requires the full remaining 5 months for complete
development
- Even at birth certain structures (nervous system, kidneys,
and liver) lack full development
 Circulatory System
Heart:
Begins beating during the 4th week after fertilization
65 bpm and increases to 140 bpm before birth
Blood cells:
- During the midportion of fetal life:
Extra marrow areas are the major sources of blood cells
- During the latter 3 months of fetal life:
Bone marrow gradually take over, while other areas
lose their ability, except for lymphocytes and plasma
cells produce in lymphoid tissue
 Respiratory System
Respiration cannot occur during fetal life
At the end of 1st trimester of pregnancy: respiratory
movements caused by tactile stimuli or fetal asphyxia
During the latter 3-4 months of pregnancy for unclearly
reasons:
- Respiratory movements are inhibited
- Lungs remain almost completely deflated
- It prevents filling of lungs with debris from meconium
- Fluid is secreted into the lungs by alveolar epithelium
up until birth keeping only clean fluid in the lungs
 Nervous System
Most of skin reflexes are present by 3rd 4th month
of pregnancy
However, functions of central nervous system that
involve cerebral cortex are still mainly undeveloped,
even at birth
Myelinization of some major tracts of central
nervous system becomes complete only after 1
year of postnatal life
 Gastrointestinal Tract
By midpregnancy: fetus ingests and absorbs large
quantities of amniotic fluid
During the last 2-3 months: gastrointestinal function
approaches that of normal neonate
Small quantities of meconium are continually
formed in gastrointestinal tract and excreted from
bowel into amniotic fluid
Meconium is composed of:
- Residue from amniotic fluid
- Excretory products from gastrointestinal mucosa and
glands
 The Kidneys
Fetal kidneys are capable of excreting urine during
at least the latter half of pregnancy and urination
occurs normally in utero
However, renal control systems for regulating:
- Extracellular fluid electrolytes balances
- Acid-base balance
are almost nonexistent until after midfetal life and
do not reach full development until a few months
after birth
Changes Associated with Embryonic and Fetal Growth
End of
Month Size / Weight Representative Changes

1 0.6 cm - Backbone and vertebral canal form

- Small buds that will develop into arms
and legs form
- Heart forms and starts beating
- Body systems begin to form
- The CNS appears at the start of the 3rd
week

2 3 cm / 1 g - Eyes far apart, eyelids fused, nose flat

- Ossifications begins
- Limbs become distinct as arms and legs
- Digits are well formed
- Major blood vessels form
- Many internal organs continue to develop
 Changes Associated with Embryonic and Fetal Growth
End of
Size / Weight Representative Changes
Month
3 7.5 cm / 30 g - Eyes almost fully developed but eyelids
still fused, nosed develops bridge, and
external ears are present
- Limbs are fully formed and nails develop
- Heartbeat can be detected
- Fetus begins to move, but it cannot be felt
by mother
- Body systems continue to develop
4 18 cm / 100 g - Head large in proportion to rest body
- Face takes on human features and hair
appears on head
- Skin bright pink
- Many bones ossified, joints begin to form
- Rapid development of body systems
 Changes Associated with Embryonic and Fetal Growth
End of
Size / Weight Representative Changes
Month
5 25 - 30 cm / - Head less disproportionate to rest of body
200 - 450 g - Fine hair (lanugo) covers body
- Skin still bright pink
- Brown fat forms and is the site of heat
production
- Fetal movements commonly felt by
mother (quickening)
- Rapid development of body systems
6 27 - 35 cm / - Head becomes even less disproportionate
550 - 800 g to rest of body
- Eyelids separate and eyelashes form
- Skin wrinkled and pink
- Type II alveolar cells begin to produce
surfactant
 Changes Associated with Embryonic and Fetal Growth
End of
Size / Weight Representative Changes
Month
7 32 - 42 cm / - Head and body more proportionate
1100 - 1350 g - Skin wrinkled and pink
- 7th months fetus (premature baby) is
capable of survival
- Fetus assumes an upside-down position
8 41 - 45 cm / - Subcutaneous fat deposited
2000 - 2300 g - Skin less wrinkled
- Testes descend into scrotum
- Bones of head are soft
- Chances of survival much greater
9 50 cm / 3200 - - Additional subcutaneous fat accumulates
3400 g - Lanugo shed
- Nails extend to finger tip, maybe beyond
 Fetal Metabolism
Fetal uses mainly glucose for energy
Fetal has a high rate of storage of fat and protein
Most of fat being synthesized from glucose, rather
than being absorbed from mothers blood
Some special problems of fetal metabolism in
relation to:
- Calcium and phosphate
- Iron
- Some vitamins
Metabolism of Calcium and Phosphate
22.5 gr of calcium and 13.5 gr of phosphorus are
accumulated during gestation:
of it accumulates during the last 4 weeks of gestation
which is coincident with the period of rapid ossification of
fetal bones as well as rapid weight gain
During the earlier part of fetal life, fetal bones are relatively
unossified and have mainly cartilagous matrix until 4th
month of pregnancy
Total amount of calcium and phosphate needed during
gestation represent only 1/50 quantities of these
substances in mothers bone minimal drain from mother
A much greater drain occurs after birth during lactation
 Metabolism of Iron
Iron accumulates in fetus more rapidly than calcium
and phosphates
Most of iron is in the form of Hb, which begin to be
formed at 3rd week after fertilization
Small amounts of iron are concentrated in mothers
uterine progestational endometrium even before
implantation, which then ingested into embryo by
trophoblastic cells for early formation of RBC
1/3 of iron in a fully developed fetus is stored in
liver that can be used for several months after birth
 Metabolism of Vitamins
Fetus needs vitamins equally as much as adult and in
some instances to a far greater extent
Vitamins function the same in fetus as in adult:
- Vit B: especially B12 and folic acid for formation of
RBC and nervous tissue as well as for overall growth
- Vit C: for appropriate formation of intercellular
substances, especially bone matrix and fibers of
connective tissue
- Vit D: probably for normal bone growth in fetus
But more important for adequate absorption of
calcium from mothers gastrointestinal tract large
quantities will be stored by fetal liver to be used for
several months after birth
 Metabolism of Vitamins..
- Vit E: necessary for normal development of early embryo
although the mechanisms are not clear
In its absence in laboratory animals: spontaneous abortion
usually occurs at an early age
- Vit K: for formation of Factor VII, pro-thrombin, and several
other blood coagulation factors
When vit K is insufficient in mother: Factor VII and pro-
thrombin become deficient in fetus as well as in mother
Because most vit K is formed by bacterial action in colon,
neonate has no adequate source of vit K prenatal storage
in fetal liver derived from mother is helpful in preventing
hemorrhage, particularly when head is traumatized by
squeezing through birth canal
 GANGGUAN
YANG MUNGKIN TIMBUL
 Errors in Sexual Differentiation

Genetic sex and phenotype sex are usually

compatible

Occasionally, discrepancies occur

between genetic and anatomic sexes
because of errors in sexual differentiation
 Errors in Sexual Differentiation..
1. If testes in a genetic male fail to properly
differentiate and secrete hormones, the result is
the development of an apparent anatomic female
in a genetic male, who, of course will be sterile.
Similarly, genetic males whose target cells lack
receptors for testosterone are feminized, even
though their testes secrete testosterone
 Errors in Sexual Differentiation..
2. Testosterone acts on Wolfian ducts to convert
them into a male reproductive tract;
If testosterone derivative dihydrotestosterone
(DHT) that responsible for masculinization of
external genitalia because of genetic deficiency of
the enzyme which converts testosterone into DHT,
results in a genetic male with testes and a male
reproductive tract but with female external
genitalia
 Errors in Sexual Differentiation..
3. Adrenal gland normally secretes a weak androgen,
dehydroepiandrosterone in insufficient quantities
to masculinize females.
If, pathologically excessive secretion of this
hormone in a genetically female fetus during
critical developmental stages imposes
differentiation of reproductive tract and genitalia
along males lines
 Endocrine Problems
If pregnant mother bearing a female child is treated
with an androgenic hormone or an androgenic tumor
develops during pregnancy hermaphroditism
The sex hormones secreted by placenta and by mothers
glands during pregnancy neonates breasts to form
milk during the first days of life, or infectious mastitis
develops
An infant born of an untreated diabetic mother
hypertrophy and hyperfunction of the islets of
Langerhans infants blood glucose concentration may
fall to lower than 20mg/dl shortly after birth
 Endocrine Problems..
Agenesis of adrenal glands or exhaustion atrophy due to
over-stimulated of adrenal glands the infant born
with hypo-functional adrenal cortices
If a pregnant woman has hyperthyroidism or treated
with excess thyroid hormone the infant born with
hypo-secreting thyroid gland; conversely if the mother
has hypothyroidism or her thyroid gland removed her
pituitary gland secrete great quantities of thyrotropin
during gestation the infant born with hyper-secreting
thyroid gland the infant born with hyperthyroidism
In fetus lacking thyroid hormone secretion cretin
dwarfism (mental retardation and bones grow poorly)