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GENERAL EMBRYOLOGY

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THE DEVELOPING HUMAN

Introduction• Human development is a continuous process that begins when

an oocyte (ovum) from a female is fertilized by a sperm (spermatozoon) from a male

• Cell division, cell migration, programmed cell death, differentiation, growth, and cell rearrangement transform the fertilized oocyte, a highly specialized, totipotent cell, a zygote, into a multicellular human being

• From a single cell to a baby in 9 months, the study of the developmental processes that take place is called Embryology

Note:• Development does not stop at birth,• Although most developmental changes occur during the

embryonic and fetal periods,• important changes occur during later periods of development:

infancy, childhood, adolescence, and early adulthood

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Terminologies• Oocyte ( ovum /egg): refers to the female germ or sex cells

produced in the ovaries• Sperm (spermatozoon): refers to the male germ cell produced in

the testes (testicles) • Zygote: This cell results from the union of an oocyte and a sperm

during fertilization A zygote or embryo is the beginning of a new human being

Developmental Periods: can be divided into prenatal (before birth) postnatal (after birth) period. Stages of prenatal development: • begins at fertilization and embryonic development ends on day 56

(8th week )• The fetal period begins on day 57 and ends when the fetus is

completely outside the mother

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Prefertilization Events Sexual Reproduction• Sexual reproduction occurs when female and male gametes

(oocyte and spermatozoon, respectively) unite at fertilization.• Gametes are direct descendants of primordial germ cells, which

are first observed in the wall of the yolk sac at 4th week of embryonic development and subsequently migrate into the future gonad region where they arrive at the end of the 5th week

• Gametes are produced by a process called gametogenesis (formation of gamete)

• In males, this process is called spermatogenesis• In females, it is called oogenesis note :• The sequence of gametogenesis is the same, but the timing of

events during meiosis differs in the two sexes.

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Primodial germ cells in wall of yolk sac

Yolk sac

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• In preparation for fertilization, germ cells undergo gametogenesis. Which include:

meiosis, to reduce the number of chromosomes and cytodifferentiation to complete their maturation

Chromosomes• A single chromosome consists of TWO characteristic regions

called arms. These include: Short arm/ p arm Long arm/ q arm • These two arms are separated by a centromere• During meiosis I, single chromosomes undergo DNA replication,

which essentially duplicates the arms. • This forms duplicated chromosomes, which consist of two sister

chromatids attached at the centromere.

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1) Ploidy and N number• Ploidy refers to the number of chromosomes in a cell • The N number refers to the amount of DNA in a cell In humans, somatic cells (cells of an organism other than the

germ cells) contain 46 single chromosomes The chromosomes occur in 23 homologous pairs, of which

one member (homologue) of each pair is of maternal origin, and the other is of paternal origin to form the diploid number of 46

Note: The term “diploid” is classically used to refer to a cell containing 46 single chromosomes

The 23 homologous pairs of chromosomes is made up of: 22 pairs of matching chromosomes called autosomes and one pair of sex chromosomes

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• If the sex pair is XX, the individual is genetically female; if the pair is XY, the individual is genetically male.

• One chromosomes of each pair is derived from the maternal gamete, the oocyte, and one from the paternal gamete, the sperm

• Thus, each gamete contains a haploid number of 23 chromosomes, and the union of the gametes at fertilization restores the diploid number of 46

Meiosis• is the cell division that takes place in the germ cells to generate

male and female gametes, sperm and egg cells, respectively• Meiosis requires two cell divisions: meiosis I and meiosis II, to reduce the number of chromosomes to the

haploid number of 23

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Meiosis 1 Events that occur during meiosis I include the following: synapsis• homologous chromosomes align themselves in pairs, this

process is called synapsis crossingover• Crossovers: this involve the interchange of chromatid

segments between paired homologous chromosomes • Segments of chromatids break and are exchanged as

homologous chromosomes separate.• As separation occurs, points of interchange are temporarily

united and form an X-like structure, a chiasma

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Stages A – D, prophase of 1st meiotic division

E – metaphaseF - AnaphaseG - Telophase(of 1st meiotic division) Cells contain

23double-structuredchromosomes

Cells resulting from 1stmeiotic division

2nd meiotic divisionMetaphase of 2nd meiotic division

DisjunctionCells resulting from 2nd meiotic division

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Summary of Meiosis I Events that occur during meiosis I include the following: Synapsis: pairing of 46 homologous duplicated chromosomes Crossing over: exchange of large segments of DNA Alignment: alignment of 46 homologous duplicated

chromosomes at the metaphase plate Disjunction: separation of 46 homologous duplicated

chromosomes from each other; centromeres do not split. Cell division: formation of two secondary gametocytes (23

duplicated chromosomes, 2N).

Meiosis II• Meiosis II. Events that occur during meiosis II include the

following:– Synapsis: absent.– Crossing over: absent.

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Summary of Meiosis I Events that occur during meiosis I include the following: Synapsis: pairing of 46 homologous duplicated chromosomes Crossing over: exchange of large segments of DNA Alignment: alignment of 46 homologous duplicated

chromosomes at the metaphase plate Disjunction: separation of 46 homologous duplicated

chromosomes from each other; centromeres do not split Cell division: formation of two secondary gametocytes (23

duplicated chromosomes, 2N).

Meiosis II• Meiosis II. Events that occur during meiosis II include the

following:– Synapsis: absent.– Crossing over: absent.

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Alignment: alignment of 23 duplicated chromosomes at the metaphase plate.

Disjunction: separation of 23 duplicated chromosomes to form 23 single chromosomes; centromeres split

Cell division: formation of four gametes (23 single chromosomes, 1N).

Note:

As a result of meiotic divisions,

(a) genetic variability is enhanced through crossover, which redistributes genetic material, and through random distribution of homologous chromosomes to the daughter cells; and

(b) (b) each germ cell contains a haploid number of chromosomes, so that at fertilization the diploid number of 46 is restored

SPERMATOGENESIS• Spermatogenesis is the sequence of events by which

spermatogonia are transformed into mature sperms.• This maturation process begins at puberty• Spermatogonia, which have been dormant in the

seminiferous tubules of the testes since the fetal period, begin to increase in number at puberty

• After several mitotic divisions, the spermatogonia grow and undergo changes

• Spermatogonia are transformed into primary spermatocytes, the largest germ cells in the seminiferous tubules.

• Each primary spermatocyte subsequently undergoes 1st meiotic division (reduction division) to form two haploid secondary spermatocytes, which are approximately half the size of primary spermatocytes

• Secondary spermatocytes then undergo a second meiotic division to form four haploid spermatids

• these haploid spermatids are approximately half the size of secondary spermatocytes.

• The spermatids are gradually transformed into four mature sperm by a process known as spermiogenesis

• The entire process of spermatogenesis, which includes spermiogenesis, takes approximately 2 months

• When spermiogenesis is complete, the sperms enter the lumina of the seminiferous tubules

• Sertoli cells lining the seminiferous tubules support and nurture the germ cells and may be involved in the regulation of spermatogenesis

• Sperms are transported passively from the seminiferous tubules to the epididymis, where they are stored and become functionally mature

• The epididymis is the elongated coiled duct along the posterior border of the testis

• It is continuous with the ductus deferens (vas deferens), which transports the sperms to the urethra

• Mature sperms are free-swimming, actively motile cells consisting of a head and a tail

• The neck of the sperm is the junction between the head and tail• The head of the sperm forms most of the bulk of the sperm and

contains the haploid nucleus. • The anterior two thirds of the nucleus is covered by the acrosome,

a caplike saccular organelle containing several enzymes

• When released, these enzymes facilitate dispersion of the follicular cells of the corona radiata and sperm penetration of the zona pellucida during fertilization

• The tail of the sperm consists of three segments: middle piece principal piece and end piece • The tail provides the motility of the sperm that assists its

transport to the site of fertilization. • The middle piece of the tail contains mitochondria, which

provide the adenosine triphosphate necessary for activity

OOGENESIS• Oogenesis (ovogenesis) is the sequence of events by which oogonia

are transformed into mature oocytes • This maturation process begins before birth and is completed after

puberty • Oogenesis continues to menopause, which is permanent cessation of

the menses (bleeding associated with the menstrual cycles)

Prenatal Maturation of Oocytes • Primordial germ cells (46, 2N) migrate from the wall of the yolk sac

and arrive in the ovary at 5th week and differentiate into oogonia (46, 2N), which populate the ovary through mitotic division.

• A majority of oogonia continue to divide by mitosis but some of them enter meiosis I and undergo DNA replication to form primary oocytes (46, 4N)

• by the 5th month of prenatal development, the total number of germ cells in the ovary reaches its maximum, which is estimated at 7 million

Note: All primary oocytes are formed by the 5th month of fetal life• At this time, cell death begins, and many oogonia as well as

primary oocytes become atretic • By the seventh month, the majority of oogonia have degenerated

except for a few near the surface Note: No oogonia are present at birth• All surviving primary oocytes have entered prophase of meiosis I,

and most of them are individually surrounded by a single layer of flattened, follicular epithelial cells

• The primary oocytes enclosed by this layer of cells constitutes a primordial follicle

• Primary oocytes begin the first meiotic division before birth, but completion of prophase does not occur until puberty

• The follicular cells surrounding the primary oocyte are believed to secrete a substance, oocyte maturation inhibitor (OMI) which keeps the meiotic process of the oocyte arrested

Postnatal Maturation of Oocytes • Beginning during puberty, usually one follicle matures each

month and ovulation occurs, except when oral contraceptives are used

• The total number of primary oocytes at birth is estimated to vary from 600,000 to 800,000

• only approximately 40,000 are present by the beginning of puberty, and fewer than 500 will be ovulated

• As the primary oocyte enlarges during puberty, the follicular epithelial cells become cuboidal in shape and then columnar, forming a primary follicle

• The primary oocyte soon becomes surrounded by a covering of amorphous acellular glycoprotein material, the zona pellucida

Note: No primary oocytes form after birth in females, in contrast to the continuous production of primary spermatocytes in males

• The primary oocytes remain dormant in the ovarian follicles until puberty

• As a follicle matures, the primary oocyte increases in size and, shortly before ovulation, the first meiotic division is completed giving rise to a secondary oocyte and the first polar body.

• Unlike the corresponding stage of spermatogenesis, there is formation 2 daughters of unequal size, this is because the division of cytoplasm is unequal, each with 23 double structured chromosomes

• The secondary oocyte receives almost all the cytoplasm and the first polar body receives very little

• The 1st polar body is a small, nonfunctional cell that soon degenerates

• The first polar body lies between the zona pellucida and the cell membrane of the secondary oocyte in the perivitelline space

• The cell then enters meiosis II but it is arrested at metaphase approximately 3 hours before ovulation

• If a sperm penetrates the secondary oocyte, the second meiotic division is completed, and most cytoplasm is again retained by one cell, the fertilized oocyte (zygote), while the 2nd polar body receive little cytoplasm

• If not fertilized, the cell degenerates approximately 24 hours after ovulation

• The other cell, the 2nd polar body, also a small nonfunctional cell, soon degenerates.

• As soon as the polar body is extruded, maturation of the oocyte is complete

Note: The first polar may also undergoes a second division

• Of these, only about 400-500 become secondary oocytes and are expelled at ovulation during the reproductive period

• Few of these oocytes, if any, are fertilized and become mature• The number of oocytes that ovulate is greatly reduced in

women who take oral contraceptives because the hormones in them prevent ovulation from occurring

Embryological terminologies

Abortion This is the premature stoppage of development and expulsion of

a conceptus from the uterus or expulsion of an embryo or fetus before it is viable-capable of living outside the uterus

The products of an abortion is called an abortus (i.e. the embryo/fetus and its membranes)

There are different types of abortion: A spontaneous abortion is one that occurs naturally and is most

common during the third week after fertilization • Approximately 15% of recognized pregnancies end in

spontaneous abortion, usually during the first 12 weeks A habitual abortion is the spontaneous expulsion of a dead or

nonviable embryo or fetus in three or more consecutive pregnancies

An induced abortion is a birth that is medically induced before 20 weeks (i.e., before the fetus is viable)

• This type of abortion refers to the expulsion of an embryo or fetus induced intentionally by drugs or mechanical means

A complete abortion is one in which all the products of conception are expelled from the uterus

A missed abortion is the retention of a conceptus in the uterus after death of the embryo or fetus.

A miscarriage is the spontaneous abortion of a fetus and its membranes before the middle of the second trimester (approximately 135 days)

Threatened abortion• This might take place before the 20th week of pregnancy• Some pregnant women have some vaginal bleeding with or

without abdominal cramps during the first three months of pregnancy

• When the symptoms indicate a miscarriage is possible, the condition is called a "threatened abortion."

• (This refers to a naturally occurring event, not medical abortions or surgical abortions

Trimester: A period of three calendar months during a pregnancy.

• Obstetricians commonly divide the 9-month period of gestation into three trimesters. The most critical stages of development occur during the first trimester (13 weeks) when embryonic and early fetal development is occurring

C L I N I C A L C O R R E L A T E S

Birth Defects and Spontaneous Abortions

Chromosomal abnormalities

May be: numerical structural note• The normal human somatic cell contains 46 chromosomes; the

normal gamete contains 23• Normal somatic cells are diploid, or 2n; normal gametes are

haploid, or n • Euploid refers to any exact multiple of n, e.g. diploid or triploid

Numerical Abnormalities

Polyploidy• Polyploidy is the addition of an extra haploid set or sets of

chromosomes (i.e., 23) to the normal diploid set of chromosomes (i.e., 46)

A. Triploidy • is a condition in which cells contain 69 chromosomes• The most common type of polyploidy is triploidy • Triploid fetuses have severe intrauterine growth retardation

with a disproportionately small trunk • Triploidy could result from the second polar body failing to

separate from the oocyte during the second meiotic division; but more likely triploidy results when an oocyte is fertilized by two sperms (dispermy) almost simultaneously

• Triploidy occurs in approximately 2% of embryos, but most of them abort spontaneously

• Triploid fetuses account for approximately 20% of chromosomally abnormal miscarriages.

• Although triploid fetuses have been born alive, this is exceptional.

• These infants all died within a few days because of multiple anomalies and low birth weight

B Tetraploidy: • is a condition in which cells contain 92 chromosomes• Usually due to failure of first mitotic division: chromosomes

replicate and divide, but all end up in the same nucleus • Tetraploid embryos abort very early, and often all that is

recovered is an empty chorionic sac, which used to be referred to as a "blighted embryo."

Aneuploidy • Aneuploidy is the addition of one chromosome (trisomy) or loss

of one chromosome (monosomy). Trisomy results in spontaneous abortion of the conceptus. However,

I. trisomy 13 (Patau syndrome),

II. trisomy 18 (Edwards syndrome),

III. trisomy 21 (Down syndrome),

IV. and Klinefelter syndrome (47,XXY) are found in the liveborn population

Monosomy also results in spontaneous abortion of the conceptus However, monosomy X chromosome (45,X; Turner syndrome) is

found in the liveborn population • Aneuploidy occurs as a result of non-disjunction during meiosis

• In meiosis, two members of a pair of homologous chromosomes normally separate during the first meiotic division so that each daughter cell receives one member of each pair

• Sometimes, however, separation does not occur (nondisjunction), and both members of a pair move into one cell

• As a result of nondisjunction of the chromosomes, one cell receives 24 chromosomes, and the other receives 22 instead of the normal 23

• When, at fertilization, a gamete having 23 chromosomes fuses with a gamete having 24 or 22 chromosomes, the result is an individual with either 47 chromosomes(trisomy) or 45 chromosomes (monosomy)

Note:• In women, the incidence of chromosomal abnormalities,

including non-disjunction, increases with age, especially at 35 years and older

Trisomy 21 (Down syndrome)• Down syndrome is usually caused by an extra copy of

chromosome 21 (trisomy21) features of children with down syndrome include• Physical growth retardation• varying degrees of mental retardation (Down syndrome IQ is

around 50, compared to children without the condition with an IQ of 100 (Mental retardation has historically been defined as an IQ below 70)

• craniofacial abnormalities, including upward slanting eyes, epicanthal folds (extra skin folds at the medial corners of the eyes), flat facies, and small ears;

• cardiac defects; and hypotonia

• Single simian crease• high incidences of leukemia, • infections,• thyroid dysfunction, • Brachycephaly• Clinodactyl of the fifth digit• and premature aging• nearly all develop signs of Alzheimer’s disease (progressive

mental deterioration manifested by loss of memory) after age 35

Incidence rate The incidence of Down syndrome is approximately • 1 in 2000 conceptuses for women under age 25• This risk increases with maternal age to 1 in 300 at age 35• and 1 in 100 at age 40

(A) Child with Down syndrome, which is characterized by a flat broad face, oblique palpebral fissures (B) broad hand with a single transverse (simian) crease

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Anterior view of the faces of dizygotic male twins that are discordant for Down syndrome (trisomy 21). The one on the right is smaller and hypotonic compared with the unaffected twin. The twin on the right developed from a zygote that contained an extra 21 chromosome. Note the characteristic facial features of Down syndrome in this infant: upslanting palpebral fissures, epicanthal folds, and flat nasal bridge

Trisomy 18 (Edwards syndrome) Patients with trisomy 18 show the following features: • mental retardation, • growth retardation• prominent occiput• congenital heart defects• low-set ears,• flexion of fingers and hands • short sternum• Micrognathia • renal anomalies • Syndactyly( webbing or fusion of fingers or toes)• and malformations of the skeletal system.

incidence rate

incidence rate of this condition is approximately 1 in 5000 newborns. • 85% are lost between 10 weeks of gestation • whereas those born alive usually die by age 2 months• Approximately 5% live beyond 1 year

Child with trisomy 18. Note the low sets ears, small mouth, deficient mandible (micrognathia) flexion of the hands, and absent/ or hypoplasia of thr radius and unla

Photograph of child with trisomy 18. Note the prominent occiput, cleft lip, micrognathia, low-set ears, and one or more flexed fingers

Trisomy 13(Patau syndrome) The main abnormalities of trisomy 13 are• mental retardation• severe central nervous system malformations• congenital heart defects• sloping forehead; malformed ears• scalp defects• bilateral cleft lip and/or palate;• Polydactyly (presence of more than 5 digits on hand or foot) eye defects, such as :• Microphthalmia • anophthalmia (congenital absence of tissue of the eyes)

Incidence rate• The incidence of this abnormality is approximately 1 in 20,000 live

births, • over 90% of the infants die in the first month after birth• Approximately 5% live beyond 1 year

Child with trisomy 13, note the bilateral cleft lip, the sloping forehead, and anophthalmia

Trisomy 13: The syndrome is commonly accompanied by polydactyly

Turner syndrome• Turner syndrome, with a 45,X karyotype, is the only

monosomy compatible with life • Even then, 98% of all fetuses with the syndrome are

spontaneously aborted• The few that survive are unmistakably female in appearance Characteritics features are the absence of ovaries (gonadal dysgenesis) short stature• Webbed neck• lymphedema of the extremities,• skeletal deformities• and a broad chest with widely spaced nipples

Patients with Turners syndrome (A) swelling in the hand

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Patients with Turners syndrome (B) prominient webbed neck and widely spaced nipples with a broad chest (C) Caused by lymphedema

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Klinefelter's syndrome ( 47, XXY)• found only in males• The non disjucntion of XX homologues is the most causative event

features• small testes• hyalinization of seminiferous tubules• sterility• often tall with disproportionately long lower limbs• Intelligence is less than in normal siblings • Approximately 40% of these males have gynecomastia

Incidence rate:

1 in 500 males

Adolescent male with Klinefelter syndrome (XXY trisomy)

Note the presence of breasts; approximately 40% of males with this syndrome have gynecomastia (development of mammary glands) and small testes

Structural chromosome abnormalities• involve one or more chromosomes usually result from

chromosome breakage.

Breaks are caused by: Environmental factors, such as viruses, radiation, and drugs• The result of breakage depends on what happens to the broken

pieces• In some cases, the broken piece of a chromosome is lost, and

the infant with partial deletion chromosome is abnormal• A well-known syndrome, caused by partial deletion is the cri-

du-chat syndrome Cri-du-chat syndrome• caused by partial deletion of the short arm of chromosome 5• children have a catlike cry, microcephaly, mental retardation,

and congenital heart disease

Microdeletions• This takes place in a few contiguous genes• This may result in microdeletion syndrome or contiguous gene

syndrome• They can be detected only by high resolution banding (high resolution banding allows detection of very small

terminal deletions in a number of disorders) Examples of microdeletion include occurs on the long arm of

chromosome 15 if the defect is inherited on the paternal chromosome, it is

called Prader-Willi syndrome• if the defect is inherited on the maternal chromosome , it is

called Angelman syndrome

Prader-Willi syndrome• affected individuals are characterized by hypotonia, obesity,

mental retardation, hypogonadism, and cryptorchidism (undescended testes)

Angelman syndrome• affected individuals are characterized by mentally retardation,

inability to speak, exhibition of poor motor development, and are prone to unprovoked and prolonged periods of laughter

Patient with Angelman syndrome resulting from a microdeletion on maternal chromosome 15

Patient with prader willi syndrome resulting from a microdeletion on paternal chromosome 15

Uterus ( womb)

introduction• is a thick-walled, pear-shaped muscular organ

dimension Length = approx 7-8 cm width = approx 5-7cm at its superior part thickness= approx 2-3 cm

parts• consists of two major parts Body, the expanded superior 2/3 Cervix, the cylindrical inferior 1/3

The body of the uterus• narrows from the fundus (the rounded, superior part of the body)

to the isthmus Note: the isthmus is the 1cm long constricted region between the

body and cervix

The cervix of the uterus • is its tapered vaginal end that is nearly cylindrical in shape• It has a lumen called the cervical canal • the cervical canal, has constricted openings at each end• At the upper constricted end is the internal os, while at the

lower constricted end is the external os• The internal os communicates with the cavity of the uterine

body,while the external os communicates with the vagina

The walls of the body of the uterus• consist of three layers Perimetrium, the thin external layer Myometrium, the thick smooth muscle layer Endometrium, the thin internal layer

• The perimetrium is firmly attached to the myometrium

The layers of the endometrium• It has 3 layers A thin superficial layer called the compact layer A thick middle layer called the spongy layer A thin deep layer called the basal layer• . The basal layer of the endometrium has its own blood supply

and is not sloughed off during menstruation• The compact and spongy layers collectively are called the

functional layer, • This functional layer disintegrate and are shed during

menstruation and after parturition (delivery of a baby)

Uterine tubes

intro

The uterine tubes extend laterally from the horns of the uterus

Dimension

approximately 10 cm long and 1 cm in diameter

Parts

the uterine tube is divided into four parts: infundibulum ampulla isthmus uterine part

functions carries oocytes from the ovaries and sperms entering from the

uterus to reach the fertilization site in the ampulla of the uterine tube

conveys the cleaving zygote to the uterine cavity

Ovaries

Intro: • The ovaries are almond-shaped reproductive glands located close to

the lateral pelvic walls on each side of the uterus

functions They produce oocytes They also produce estrogen and progesterone, Estrogen and progesterone are hormones responsible for the

development of secondary sex characteristics and regulation of pregnancy

Female reproductive cycles• females undergo reproductive cycles (sexual cycles), involving

activities of the hypothalamus of the brain, pituitary gland (hypophysis), ovaries, uterus, uterine tubes, vagina, and mammary glands and this commences at purberty

• These monthly cycles prepare the reproductive system for pregnancy

• Gonadotropin-releasing hormone is synthesized by neurosecretory cells in the hypothalamus and is carried by the hypophysial portal system to the anterior lobe of the pituitary gland

• Gonadotropin-releasing hormone stimulates the release of 2 hormones namely:

Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)• These 2 hormones act on the ovaries: Follicle-stimulating hormone (FSH) stimulates the development of ovarian follicles and the production of estrogen by the follicular cells. Luteinizing hormone (LH) serves as the "trigger" for ovulation (release of secondary oocyte) stimulates the follicular cells and corpus luteum to produce

progesterone

Ovarian cycle• These are cyclic changes in the ovaries, and these changes are

produced by FSH and LH• These changes include:

I. development of follicles

II. ovulation, and

III. Formation of the corpus luteum

Development of follicles • Development of an ovarian follicle is characterized by:

I. Growth and differentiation of primary oocyte

II. Proliferation of follicular cells

III. Formation of zona pellucida

IV. Development of the theca folliculi

• As primordial follicles begin to grow, surrounding follicular cells change from flat to cuboidal in shape and then columnar, forming a primary follicle

• Also, follicular (granulosa) cells and the oocyte secrete a layer of glycoproteins on the surface of the oocyte, forming the zona pellucida

Development of theca folliculi• As the primary follicle continues to grow, the adjacent

(surounding) connective tissue organizes into a capsule, called the theca folliculi

• cells of the theca folliculi then differenciate into: an inner layer of secretory cells, called the theca interna and an outer fibrous capsule,called the theca externa

• As development continues, fluid-filled spaces appear between follicular (granulosa) cells

• The fluid filled space is crescent-shaped, but with time, it enlarges which coalesce to form a single large cavity, the antrum, which contains follicular fluid

• After the antrum forms, the ovarian follicle is called a vesicular or secondary follicle

• The primary oocyte is pushed to one side of the follicle, where it is surrounded by a mound of follicular cells, the cumulus oophorus, that projects into the antrum

• The secondary/ vesicular follicular continues to grow and become matured having a diameter of about 25mm or more

• At maturity, it is called the mature vesicular/ mature secondary or Graafian follicle

• The early development of ovarian follicles is induced by FSH, but final stages of maturation require LH as well

• Growing follicles produce estrogen, hormone that regulates development and function of the reproductive organs

Ovulation This is the release of an oocyte from the ovarian follicle• In a few before ovulation, under the influence of FSH and LH, the

secondary follicle grows rapidly to a diameter of about 25 mm to become mature vesicular/ mature secondary or Graafian follicle

Coincident with final development of the vesicular follicle, there is an abrupt increase in LH that causes the primary oocyte to complete meiosis I and the follicle to enter the preovulatory mature vesicular stage

Meiosis II is also initiated, but the oocyte is arrested in metaphase approximately 3 hours before ovulation

In the meantime, the surface of the ovary begins to bulge locally, and at the apex, an avascular spot, the stigma, appears

For the oocyte to be released, 2 events occur which are caused by LH surge:

I. The high concentration of LH increases collagenase activity, resulting in digestion of collagen fibers (connective tissue) surrounding the follicle

II. Prostaglandin levels also increase in response to the LH surge and cause local muscular contractions in the ovarian wall

• Those contractions extrude the oocyte, which together with its surrounding follicular (granulosa) cells from the region of the cumulus oophorus,

• this causes ovulation in which oocyte floats out of the ovary• Some of the cumulus oophorus cells then rearrange themselves

around the zona pellucida to form the corona radiata

C l i n i c a l c o r r e l a t e s During ovulation, some women feel a slight pain called

mittelschmerz also known as middle pain because it normally occurs near the middle of the menstrual cycle

A variable amount of abdominal pain, mittelschmerz , accompanies ovulation in some women. In these cases, ovulation results in slight bleeding into the peritoneal cavity, which results in sudden constant pain in the lower abdomen.

Mittelschmerz may be used as a symptom of ovulation, but there are better symptoms, such as the slight drop in basal body temperature

Some women fail to ovulate, this is called anovulation, because of a low concentration of gonadotropins

• In these cases, administration of an agent to stimulate gonadotropin release and hence ovulation can be employed

• Although such drugs are effective, they often produce multiple ovulations, so that the risk of multiple pregnancies is 10 times higher in these women than in the general population

Theca interna Luteal cells

fibrin

Blood vessels

antrum

Theca externa

C: CORPUS LUTEUM B: OVULATIONA : PREOVULATORY FOLLICLE

Corpus Luteum• Shortly after ovulation, the walls of the ovarian follicle and theca

folliculi collapse and are thrown into folds are vascularized by surrounding vessels

• Under LH influence, they develop into a glandular structure, these cells develop a yellowish pigment and change into lutein cells the corpus luteum, which secretes progesterone and some estrogen

• progesterone and estrogen, cause the endometrial glands to secrete and prepare the endometrium for implantation of the blastocyst

• If the oocyte is fertilized, the corpus luteum enlarges to form a corpus luteum of pregnancy and increases its hormone production.

• Degeneration of the corpus luteum is prevented by human chorionic gonadotropin

• The corpus luteum of pregnancy remains functionally active throughout the first 20 weeks of pregnancy

• If the oocyte is not fertilized, the corpus luteum involutes and degenerates 10 to 12 days after ovulation

• It is then called a corpus luteum of menstruation • The corpus luteum is subsequently transformed into white scar

tissue in the ovary, a corpus albicans• Except during pregnancy, ovarian cycles normally persist

throughout the reproductive life of women and terminate at menopause, the permanent cessation of menstruation, usually between the ages of 48 and 55