5. Fertilization-Early Embryo Development.ppt

Fertilization

1. Fertilization-early Embryonic
Development
PRESENTED BY: SIAMANI BRIAN
(CURTESY: Prof. Bellington Vwalika
Consultant Obstetrician/Gynaecologist –UTH,
LUSAKA) 1

2. Mitosis
The process of cell division which
results in the production of two
daughter cells from a single parent
cell.
The daughter cells are identical to
one another and to the original
parent cell.
2

3. Mitosis can be divided into stages
4 Phases:-
Prophase
Metaphase
Anaphase
Telophase
3

4. Prophase
The cell prepares for nuclear division
•Animal Cell
–Packages DNA into
chromosomes
4

5. Metaphase
The cell prepares chromosomes for
division
•Animal Cell
–Chromosomes line up at
the center of the cell
–Spindle fibers attach
from daughter cells to
chromosomes at the
centromere
5

6. Metaphase
Animal Cell
Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm
6

7. Anaphase
The chromosomes divide
•Animal Cell
–Spindle fibers pull
chromosomes apart
–½ of each chromosome
(called chromotid)
moves to each daughter
cell
7

8. Anaphase
Animal Cell
Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm
8

9. Telophase
The cytoplasm divides
•Animal Cell
–DNA spreads out
–2 nuclei form
–Cell wall pinches in to
form the 2 new daughter
cells
9

10. Interphase
occurs before mitosis begins
•Chromosomes are copied (# doubles)
•Chromosomes appear as threadlike coils
(chromatin) at the start, but each chromosome
and its copy(sister chromosome) change to sister
chromatids at end of this phase
CELL
MEMBRANENucleus
Cytoplasm
10

11. Prophase
1
st
step in Mitosis
•begins (cell begins to divide)
•(or poles) appear and begin to move to opposite
end of the cell.
•form between the poles.
Centrioles
Sister chromatids
Spindle fibers11

12. Metaphase
2
nd
step in Mitosis
•Chromatids (or pairs of chromosomes) attach to the
spindle fibers.
Centrioles
Spindle fibers
12

13. Telophase
4th step in Mitosis
•Two new nuclei form.
•Chromosomes appear as chromatin (threads rather
than rods).
•Mitosis ends.
NucleiNuclei
Chromatin
13

14. Mitosis
Stage Chromosomes Other events
Prophase •Consist of 2 chromatids joined by
centromere
•Condense (shorter and fatter)
•Become visible
•Nuclear envelope disintergrates
•Centrioles at poles
•Spindle starts to form
Metaphase •Still consist of 2 chromatids joined
by centromere
•Centromeres attach chromatid
pairs to spindle fibres
•Chromatid pairs line up along the
equator of the cell
•Spindle formed
Anaphase •Centromere holding chromatids
splits to separate the chromatids
(when split = chromosomes)
•Chromosomes pulled to opposite
poles by spindle fibres contracting
•Pulled centromere first
•Spindle fibres contract
Telophase •Become long and thin = not visible•Nuclear envelop forms around
chromosomes at each end of cell
•Spindle disintergrates
14

15. Meiosis
Meiosis is the type of cell division by
which germ cells (eggs and sperm) are
produced.
One parent cell produces four daughter
cells.
Daughter cells have half the number of
chromosomes found in the original
parent cell
15

16. Meiosis
During meiosis, DNA replicates
once, but the nucleus divides
twice.
16

17. Meiosis
Four stages can be described for
each division of the nucleus.
17

18. First Division of Meiosis
•Prophase 1: Each chromosome duplicates and remains
closely associated. These are called sister chromatids.
•Metaphase 1: Chromosomes align at the center of the cell.
•Anaphase 1: Chromosome pairs separate with sister
chromatids remaining together.
•Telophase 1: Two daughter cells are formed with each
daughter containing only one chromosome of the
chromosome pair.
18

19. Second Division of Meiosis
•Prophase 2: DNA does not replicate.
•Metaphase 2: Chromosomes line up at the center of the
cell
•Anaphase 2: Centromeres divide and sister chromatids
move separately to each pole.

•Telophase 2: Cell division is complete.
Four haploid daughter cells are formed.
19

20. Meiosis Overview
•Meiosis is the process of going from a diploid
cell to a haploid cell
–N = haploid number of any genome
–For humans n = 23
–Your diploid chromosome count is
•2n = 46
20

21. Homologous pair of chromosomes in diploid cell
Duplication
Sister Chromatids
Separation of Homologous Chromosomes
Meiosis I
Separation of Sister Chromatids
Meiosis II
One diploid cell with 2 chromosomes
21

22. Meiosis In Males
•meiosis occurs in the testis
–Mature sperm begin as spermatogonium diploid cells
•When a male reaches puberty hormones in the brain
signal the testis to make testosterone
•Testosterone then prompts
–Maturation of sperm
–Growth of muscles
–Increased bone density
–Deepening of voice
–Increased hair growth
22

23. How Hormone Signals Work
23

24. Testosterone Levels
Over Time
•Once puberty is reached testosterone levels
decrease gradually and slowly over time
24

25. Meiosis In Females
•Meiosis begins in the ovaries
–Mature oocytes (eggs) develop from diploid oogonium cells
•When a female reaches puberty hormones in the brain
signal the ovaries to develop mature eggs
•As a follicle develops two major hormones are released
–Estrogen
–Progesterone
25

26. Female Sex Hormones
•Progesterone
–Readies the uterus for implantation
•Estrogen prompts
–Development of breasts
–Appearance of pubic hair
–Increase in fat beneath the skin
–Widening and lightening of the pelvis
26

27. Part II
Mechanisms of Meiosis
27

28. Color Scheme for Chromosomes
•We will begin with a hypothetical cell which contains 6
chromosomes
•Homologous chromosomes are the same size, but not
directly attached to one another
•One homolog will be solid color the other homolog will
be the same color with a pattern
•Sister chromatids are of course attached and the same
color
28

29. Hypothetical Spermatogonium or Oogonium Cell
How many chromosome does this cell have?
What is n for this cell?
When this cell goes through Meiosis I and II
how many chromosomes will it have?
29

30. Step 1 Duplication of the chromosomes is S Phase
30

31. Meiosis I
Separation of Homologs
31

32. 32

33. Anaphase I
•After a cell completes anaphase I the cell
is haploid
•Now you only have one copy of every
gene, it is a duplicated copy but still just
one copy
33
Hypothetically – the black dash represents a gene for eye color.
Since the separation of the homologs your cell now has only one
gene for eye color and not two as found in the diploid cell

34. Anaphase I
•Also during anaphase I in males the Y
chromosome pairs with the X chromosome
•After these separate the cell is haploid and
has either one duplicated copy of X or one
duplicated copy of Y
34

35. Meiosis II
Separation of Sisters
35

36. 36

37. Meiosis I Overview
37

38. Meiosis II Overview
38

39. Meiosis In Males
•Sperm formation occurs in
specialized cells in the testis
(Sertoli cells)
•It takes approximately 30(or
72) days for a mature sperm
cell to form
•Sperm production begins in
puberty and continues until
death
•Leydig cells produce
testosterone in the presence
of LH
•Sertoli cells are activated by
FSH. They are responsible for
spermatogenesis.
39
Many Complex and physiological
and morphological changes
happen during sperm development

40. Meiosis in Females
•Females produce eggs from puberty until
menopause
•Female oogonia undergo meiosis but do not
complete meiosis II unless the egg becomes
fertilized
–Arrested in metaphase II
40

41. Begins to undergo meiosis in the embryo
Arrested in Prophase I until puberty
Is this cell diploid or haploid
Oogonia
Follicle begins to form
Primary Oocyte
Finishes Meiosis I
At puberty Primary Oocyte can complete
Meiosis I
Polar Body
Secondary Oocyte
Arrested at Metaphase II
Mature Follicle
41

42. Meiosis In Females
•Polar bodies are
not
functional
•They only
contain
genetic
material and
are reabsorbed
by the body
42

43. Meiosis patterns in mammals differ for
males and females
•Gametogenesis, the production of gametes by
meiosis, differs in females and males
•Sperm are small and motile and are produced
throughout the life of a sexually mature male
•Spermatogenesis is production of mature sperm
43

44. Fig. 46-12b
Epididymis
Seminiferous tubule
Sertoli cell
nucleus
Testis
Cross section
of seminiferous
tubule
Spermatogonium
Primary spermatocyte
Secondary spermatocyte
Spermatids
(two stages)
Sperm
Lumen of
seminiferous tubule
44

45. Fig. 46-12c
Primordial germ cell in embryo
Mitotic divisions
Spermatogonial
stem cell
Mitotic divisions
Spermatogonium
Mitotic divisions
Primary spermatocyte
Meiosis I
Secondary spermatocyte
Meiosis II
Early
spermatid
Differentiation (Sertoli
cells provide nutrients)
Sperm
2n
2n
2n
n n
nn nn
n n n n
45

46. Fig. 46-12d
46

47. •Eggs contain stored nutrients and are much larger
•Oogenesis is development of mature oocytes
(eggs) and can take many years
47

48. Fig. 46-12g
Primordial germ cell
Mitotic divisions
Oogonium
Mitotic divisions
Primary oocyte
(present at birth), arrested
in prophase of meiosis I
Completion of meiosis I
and onset of meiosis II
Secondary oocyte,
arrested at metaphase of
meiosis II
First
polar
body
Ovulation, sperm entry
Completion of meiosis II
Second
polar
body
Fertilized egg
2n
2n
n
n
n
n
In embryo
48

49. •Spermatogenesis differs from oogenesis:
–In oogenesis, one egg forms from each cycle of
meiosis; in spermatogenesis four sperm form from
each cycle of meiosis
–Oogenesis ceases later in life in females;
spermatogenesis continues throughout the adult life
of males
–Oogenesis has long interruptions; spermatogenesis
produces sperm from precursor cells in a continuous
sequence
49

50. The interplay of tropic and sex
hormones regulates mammalian
reproduction
•Human reproduction is coordinated by hormones
from the hypothalamus, anterior pituitary, and
gonads
•Gonadotropin-releasing hormone (GnRH) is
secreted by the hypothalamus and directs the
release of FSH and LH from the anterior pituitary
•FSH and LH regulate processes in the gonads and
the production of sex hormones
50

51. •The sex hormones are androgens, estrogens, and
progesterone
•Sex hormones regulate:
–The development of primary sex characteristics
during embryogenesis
–The development of secondary sex characteristics at
puberty
–Sexual behavior and sex drive
51

52. Fertilization
52

53. Fertilization:
the fusion of the sperm cell nucleus
with the egg cell nucleus to produce
a zygote (fertilized egg)
53

54. Fertilization:
•External
•Occurs outside of the body of the female
•Increased number of eggs produced to insure
the survival of the species
•Ex) fish and amphibians
54

55. Fertilization:
•Internal
•Occurs inside the body of the female
•Fewer number of eggs are produced
•Increased parental care insures species
survival
•Ex) mammals, reptiles, birds
55

56. Fertilization:
•fertilization in
mammals occurs
in the oviduct
•The ova is viable
for
approximately
24 hours after
ovulation
56

57. 57

58. Fig. 47-3-5
Basal body
(centriole)
Sperm
head
Sperm-binding
receptors
Acrosome
Jelly coat
Vitelline layer
Egg plasma
membrane
Hydrolytic enzymes
Acrosomal
process
Actin
filament
Sperm
nucleus
Sperm plasma
membrane
Fused
plasma
membranes
Fertilization
envelope
Cortical
granule
Perivitelline
space
EGG CYTOPLASM
58

59. Fig. 47-UN1
Sperm-egg fusion and depolarization
of egg membrane (fast block to
polyspermy)
Cortical granule release
(cortical reaction)
Formation of fertilization envelope
(slow block to polyspermy)
59

60. Pregnancy
60
If the egg is fertilized, the uterus lining must not break down otherwise the
fertilized egg will not develop.
corpus luteum (structure that develops
after the ovum is discharged but
degenerates if no pregnancy):
continues to produce
progesterone and oestrogen
egg fertilized:
uterus lining
maintained, egg
implanted
progesterone memo
To: uterus
From: corpus luteum
Maintain uterus lining.
oestrogen memo
To: pituitary
From: corpus luteum
Don’t send FSH.

61. Implantation
•After approximately a week,
the developing embryo is
implanted into the uterus
Three stages of prenatal
development
•Pre-embryonic:0-3 weeks
•Embryo: conception to 8
weeks
•Fetus: Onwards

61

62. Embryonic Development
62

63. 63

64. Embryo:
•a multicellular organism in the early stages of
development
2 four cell stage embryos
Eight cell stage embryo
64

65. Fig. 47-6
(a) Fertilized egg(b) Four-cell stage(c) Early blastula(d) Later blastula
65

66. Embryo:
The beginning developmental processes are
always the same in all animals:
1) cleavage
2) growth
3) differentiation
66

67. Embryo:
•after fertilization
the diploid
ZYGOTE
undergoes
cleavage divisions
in the oviduct
67

68. Cleavage
the first series of cell divisions by mitosis
after fertilization
Cell division is rapid, new cells do not take
time for the growth phase G
1
cell growth does not occur so cells
decrease in size with each cleavage
division
68

69. Cleavage divisions
69

70. •Morula forms (solid ball of cells)
•Blastula forms (hollow ball of cells)
•Cells begin to grow before dividing
70

71. 71

72. Differentation
•Gastrulation: one side
of the blastula
invaginates (indents)
forming a gastrula
•Three cell layers form
72

73. Differentiation
73

74. Fig. 47-16-5
Yolk sac
Mesoderm
Amnion
Chorion
Ectoderm
Extraembryonic
mesoderm
Trophoblast
Endoderm
Hypoblast
Expanding
region of
trophoblast
Epiblast
Maternal
blood
vessel
Allantois
Trophoblast
Hypoblast
Endometrial
epithelium
(uterine lining)
Inner cell mass
Blastocoel
Uterus
Epiblast
Amniotic
cavity
Expanding
region of
trophoblast
Yolk sac (from
hypoblast)
Chorion (from
trophoblast)
Extraembryonic
mesoderm cells
(from epiblast)
74

75. Differentiation
•The changing of unspecialized embryonic cells
into the specialized cells, tissues and organs of
a multicellular animal
75

76. Germ Layers
•EctodermOuter layer
•Nervous system including brain, spinal
cord and nerves
•Lining of the mouth, nostrils, and anus
•Epidermis of skin, sweat glands, hair, nails
76

77. Germ Layers
•Mesoderm Middle Layer
•Bones and muscles
•Blood and blood vessels
•Reproductive and excretory systems
•Inner layer (dermis) of skin
77

78. Germ Layers
•EndodermInner Layer
•Lining of digestive tract
•Lining of trachea, bronchi, and lungs
•Liver, pancreas
•Thyroid, parathyroid, thymus, urinary bladder
78

79. Placenta
•organ that
forms from the
embryo and
the uterus
79

80. Placenta
•contains blood vessels from the
mother and the developing baby
80

81. placenta
•Fully formed at 12 weeks
–1
st
wave of trophoblastic invasion at 12 weeks
–Second phase at 16 weeks
81

82. Placenta
•Oxygen & nutrients diffuse from the
mother’s blood vessels into the baby’s
blood vessels
•Wastes diffuse from the baby’s blood
vessels into the mother’s blood vessels
82

83. The placenta and fetal membranes
•Human placenta described as haemochorial
because of direct contact of chorion with
maternal blood
•It is deciduate because some maternal tissue
is shed at parturition
•Attached to uterine wall and link of mother
and fetus via umbilical cord
83

84. •Develops from 2 sources
•Principal component is foetal which develops from
chorion frondosum and maternal component consist
of decidual basalis
•Process begins at 6
th
week and is completed by the
12
th
week
•Until endof the 16
th
week ,the placenta grows both in
thickness and circumference due to growth of
chorionic villi with accompanying expansion of
intervillous space
84

85. Placenta at term
•Gross anatomy
–Circular disc 15-20 diameter 2.5cm thick at center
–Weighs 500gm ,proportion to weight of fetus of
1:6
–Has fetal and materna surfaces
–Fetal surface
•Covered by smooth amnion with cord attached near
centre
85

86. •Maternal surface
–Is rough and spongy
–Mapped out into 15-20 lobes or cotyledons
•From chorionic plate arise the stem villi and extend
to the basal plate.These are the functional units of
the placenta
•Each villi is made up of outer syncytiotrophoblast(for
transfer),cytotrophoblast(for synthesis),central
stroma containing fetal capillaries etc and basement
membrane
86

87. Placental circulation
•2-uteroplacental and foeto-placental
circulation
•Utero-placental concerned with circulaton of
maternal blood through intervillous space-
replaced every 3 to 4 times per minute
–Villi depend on maternal blood for nutrition ,thus
it is possible for chorionic villi to survive for a
varying period even after the foetus is dead
87

88. –120-200 spiral arteries open into intervillous
space by piercing the basal plate
–There is cytotrophoblastic invasion into spiral
arteries upto the intramyometrial segment and is
completed by 16 weeks
•The umbilical cord has 2 arteries and one
vein.The arteries carry impure blood and veins
carry pure blood
88

89. Placental function
1.Transfer of nutrients and waste products between mother and foetus
that is:respiratory,excretory,nutritive
2.Produces or metabolises the hormones and enzymes necessary to
maintain the pregnancy
Human Chorionic Gonadotropin Hormone (HCG)- Prevents
menstruation
Human placental lactogen (hPL)- helps in the process of providing
nutrition to the fetus
Estrogen- helps maintain a healthy pregnancy
Progestin- support the endometrium to provide conducive
environment for fetal survival; and to suppress contractility in
uterine smooth muscles
3.Barrier function
4 . immunological function
89

90. •Transfer function dependent on:
–Physical properties of substances
–Extent and integrity of placental membrane
–Rate of blood flow,foetal and maternal on either
side of exchange membrane
•Mechanisms involved in transfer of substances
include: simple diffusion,active transfer,pinocytosis
and leakage through broken placental membrane

90

91. •Respiratory function-input of oxygen and
output of carbon dioxide by simple diffusion
across foetal membrane
•Excretory function of products from foetus
such as urea,uric acid and creatinine to
maternal blood by simple diffusion
•Nutritive foetus obtains nutrients from
maternal blood , so have diet rich in :
91

92. –Glucose for energy transferred by facilitated
diffusion
–Lipids for growth.Dual origin ,directly from mother
and also synthesised by foetus
–Amino acids actively transported through
enzymatic action
–Water and electrolytes-Na,K and Cl by simple
diffusion while Ca,Fe and phosphorus actively
transported.Water soluble vitamins actively
transferred
92

93. •Enzymatic function-numerous enzymes
elaborated in the placenta such as
oxytocinase and phospholipase A
2
•Barrier function – fetal membrane protects
fetus against noxious agents .In general
substances of high molecular weight of more
than 500 daltons are held up but there are
exceptions
93

94. The foetal membranes
•Consist of 2 layers –outer chorion and inner
amnion
•Chorion ends at edge of placenta-has no
vessels or nerves
•Amnion inner and in contact with liqour amnii
–Functions
•Contribute to the formation of liquor amnii
•Intact membranes prevent ascending uterine infection
94

95. •Facilitate dilatation of the cervix during labour
•Has got enzymatic activity for steroid
hormone metabolism
•Rich source of glycerophospholipids
containing arachidonic acid –precursor of
prostaglandin E2 and F2alpha
95

96. Amniotic fluid
•Origin- precise origin is unknown.Theories include:
–As a transudate from maternal serum across
foetal membranes or from maternal circulation in
the placenta
–As a transudate across the umbilical cord or from
foetal circulation in the placenta or secretion from
amniotic epithelium
–Contribution from foetal urine-the fetus drinks
about 400ml of liqour everyday at term and
passes equal amount in urine
96

97. –Secretion from tracheobronchial tree and across
the foetal skin before the skin becomes keratinised
at the 20
th
week
•Measures 30ml at 10 weeks and 300ml at 20
weeks reaching max of 1 litre at 36-38 weeks
•Physical features
–Colourless but near term becomes pale straw
coloured due lanugo and fetal squames.May be
turbid due to vernix caseosa
97

98. •Abnormal colour
–Meconium stained (green) due to foetal distress
–Golden colour in RH incompatibility due to
excessive hemolysis of feta RBC and hence
haemoglobin formation
–Greenish yellow in post maturity
–Dark coloured in concealed accidental
hemorrhage due to contamination of blood
–Dark brown(tobacco juice) amniotic fluid is found
in IUFD.Dark colour is due to frequent presence of
old HbA
98

99. •Functions
–Acts as shock absorber ,protecting the fetus from
possible extragenous injury
–Maintains an even pressure
–Distends amniotic sac and thereby allows for growth
and free movement of the fetus and prevents
adhesion between the foetal parts and amniotic sac
–Its nutritive value is negligible because of small
amount of protein and salt,however water supply to
foetus is quite adequate
99

100. •During labour
–Amnion and chorion are combined to form a
hydrostatic wedge which helps in dilatation of
the cervix
–During contration prevents marked interference
with placental circulation so long membranes
remain intact
–Flushes birth canal after first stage of labour and
by its aseptic and bactericidal action protects the
foetus and prevents ascending infection
100

101. •Clinical importance
–Study of it provides useful information about
status of foetus
–Intra amniotic instillation of chemicals used as a
method for induction of abortion
–Excess or less gives rise to hydramnios and
oligohydramnios
–ARM with drainage is helpful in induction of
labour
101

102. Umbilical Cord
•two arteries and a
vein Connects the
fetus to the
placenta
102

103. Amniotic Sac
•Contains fluid
(amniotic fluid) that
protects fetus by
giving it a stable
environment and
absorbing shock
103

104. •By the end of the 8
th

week of pregnancy
the embryo is called a
fetus and all of the
major structures are
present
104

105. Later Stages of Fetal Development
105

106. •After blastocyst formation, the embryo implants
into the endometrium
•The embryo releases human chorionic
gonadotropin (hCG), which prevents menstruation
•Pregnancy, or gestation, is the condition of
carrying one or more embryos in the uterus
•Duration of pregnancy in other species correlates
with body size and maturity of the young at birth
106

107. First Trimester
Human gestation can be divided into three trimesters of
about three months each
The first trimester is the time of most radical change for
both the mother and the embryo
During implantation, the endometrium grows over the
blastocyst
During its first 2 to 4 weeks, the embryo obtains nutrients
directly from the endometrium
Meanwhile, the outer layer of the blastocyst, called the
trophoblast, mingles with the endometrium and
eventually forms the placenta
Blood from the embryo travels to the placenta through
arteries of the umbilical cord and returns via the umbilical
vein
107

108. Fig. 46-16
Placenta
Uterus
Umbilical cord
Chorionic villus,
containing fetal
capillaries
Maternal blood
pools
Maternal
arteries
Maternal
veins
Maternal
portion
of placenta
Fetal arteriole
Fetal venule
Umbilical cord
Fetal
portion of
placenta
(chorion)
Umbilical
arteries
Umbilical
vein
108

109. Splitting of the embryo during the first month of
development results in genetically identical twins
Release and fertilization of two eggs results in fraternal
and genetically distinct twins
The first trimester is the main period of organogenesis,
development of the body organs
All the major structures are present by 8 weeks, and
the embryo is called a fetus
•Changes occur in the mother
Growth of the placenta
Cessation of ovulation and the menstrual cycle
Breast enlargement
Nausea is also very common
109

110. Human gestation
• the period
between
fertilization and
birth
•approximately 38-
40 weeks
110

111. Teratogens
•Substances that may harm the
developing fetus and result in the
formation of birth defects
–Pre-embryonic (0-3 weeks) phase follow ‘all or
none principle’
–Embryonic phase(4-8weeks)- fetus is affected
–Fetal stage >8 weeks till delivery
111

112. Teratogens include:
•Alcohol, certain drugs/medications,
infections, and certain chemicals
112

113. 113

114. Fetal Alcohol Syndrome
Can result in mental retardation / learning disability
Facial Features
•Epicanthal folds
•Small, widely spaced eyes
•Flat midface
•Short, upturned nose
•Smooth, wide philtrum
•Thin upper lip
•
Underdeveloped jaw
114

115. Cleft Lip / Palate
•maternal alcohol consumption and maternal
smoking during the early stages of pregnancy have
been shown to increase the risk of developing
orofacial clefts
•http://www.hopeforkids.com/body_cleft_lip%5B1%5D.html#
115

116. How do twins form???
116

117. Monozygotic Twins
(Identical Twins)
•One egg is fertilized by one sperm
•Embryo splits into two during the early stages of
development
• Have identical genes and must be of the same sex
•(Incidence: about 3 in every 1000 births)
117

118. 118

119. Dizygotic Twins
(Fraternal Twins)
•Two eggs are ovulated and each is fertilized by a
sperm cell
•No more genetically similar than any other sibling in
the family (can be same/different sexes)
•Maternal age, use of assisted reproductive
technologies are factors
•Incidence (6.7/1000 births in Japan to 40/1000 births
in Nigeria)
119

120. Thank you for
your attention !
120

121. Any questions?
121