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Fertilization and Fetal Development

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    Chapter 4: FERTILIZATION AND FETALDEVELOPMENT

    I. FERTILIZATION

    A. Fertilization is the union

    of mature egg cell (ovum)and sperm cell happening in

    the ampulla (outer third) of

    the fallopian tube resulting

    in a fertilized ovum known

    as the zygote.

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    B. It is also termed

    conception, fecundation, and

    impregnation.

    C. The movement of the

    sperms caused by flagellar

    action is believed to maintainthe sperms in suspension and

    to maintain the sperms in

    suspension and to facilitate

    transport.

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    D. Each sperm reaches the site of

    fertilization in the ampulla of the

    fallopian tube shortly after

    ejaculation, often only within 5

    minutes. But on average, a time of 4to 6 hours seems more reasonable.

    E. Sperms must be in the genital

    tract 4 to 6 hours before they are ableto fertilize an egg, It is during this

    period when the enzyme needed to

    dissolve the cement substance

    (hyaluronic acid) that holds together

    the cells covering the ovum isactivated. This enzymes is called

    hyaluronidase.

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    F. The sperm must undergo 2 processes before fertilization:

    1. Sperm capacitation: the process by which the sperm becomes

    hypermobli and there is a breakdown of the plasma membrane and

    exposes the acrosomal membrane/ covering of the sperm head

    allowing the sperm to bind with the zona pellucida of the ovum.

    2. Acrosomal Reaction: follows capacitation; the acrosomal covering of

    the head of the sperm contains hyaluronidase. So as millions of spermssurrounds the ovum, they deposit minute amounts of hyaluronidase in

    the corona radiata, the outer layer of the ovum, which allows the

    sperm head to penetrate the ovum

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    G. As soon as the sperm penetrates the zona

    pellucida and makes contact with the vitelline

    membrane of the ovum, a cellular change

    occurs in the ovum that inhibits other spermsto penetrate. This cellular change is mediated

    by release of material from the cortical

    granules, organelles found just below the egg

    surface

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    H. Fertilization occurs

    when the male

    pronucleus, thus the

    chromosome diploidnumber (46) is restored

    and a new cell, the

    zygote, is created with

    a new combination ofgenetic material which

    creates a unique

    individual different

    from the parents and

    anyone else.

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    II. CLEAVAGE/MITOSIS

    A. Zygote: the cell that resultsfrom the fertilization of the

    ovum by a spermatozoan. This

    cell undergoes mitosis which is

    the process of cell replication

    where each chromosome splits

    longitudinally to form a

    double-stranded structure.

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    B. Cleavage: series of

    mitotic cell division by

    the zygote

    C. Blastomeres:

    daughter cells arising

    from the mitotic cell

    division of the zygote

    92-cell, 4-cell, 8-cellblastomeres)

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    D. Morula: solid ball of

    cells produced by 16 or so

    blastomeres; called the

    traveling form because itis ion this form when it

    migrates thru the fallopian

    tube and reaches the

    uterine cavity about 3 to 4after ovulation.

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    E. Blastocyst: a fluid-filled cavity that

    reaches the uterine cavity

    Over the next 3 to 4 days of development,

    a differentiation of cells as to their specific

    potencies occurs. The reorganization ofthe morula follows forming a blastocyst.

    This is the stage when there is already a

    cavity in the morula called the blastocoels,

    and when it enters the uterine cavity. The

    cavity enlarges and pushes the morulacells into an outer layer of cells called the

    trophoblast. Along with this is an inner

    cells mass attached to one side of the

    blastocyst. The divisions and the

    reorganization have already consumed

    energy stores available in the zygote, such

    that it becomes necessary for the

    blastocyst to embed or implant in the

    uterine wall. This is necessary for it to

    obtain nourishment for its further

    development.

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    III. IMPLANTATION

    A. Also called Nidation

    B. Time: 6 to 9 days after

    fertilization

    C. Site: upper fundal portion or

    upper one-third of the uterus; canbe anterior 9towards the mothers

    front) or posterior. Abnormal

    implantation sites are the fallopian

    tubes which leads to ectopic

    pregnancy and the lower uterinesegment which causes placenta

    previa.

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    IV. THE PLACENTA

    A. Dimension

    1. Discoid: 15 to 20 cm in diameter and 2 to 3 cm thickness

    2. Location: in the uterus, anteriorly or posteriroly near the

    fundus.

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    3. Fetal Side: covered with

    amnion; beneath it the fetal

    vessels course with the

    arteries passing over the

    veins. Amnion: 0.02 to 0.05mm in thickness; a sac that

    engulfs the growing fetus.

    Amniotic fluid: clear fluid

    that collects within theamniotic cavity

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    4. Maternal Side; divided into

    irregular lobes; consist of

    fibrous tissue with sparse

    vessels confined mainly to thebase

    5. Average weight at term 500

    gm

    6. Feto-placental weight ratio atterm - 6:1

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    B. Placenta is formed by the union of the pregnancy; thickens in pregnancy w/ depth of 5 to 10

    mm.

    1. Decidua Basalis: portion of deciduas directly beneath the site of implantation, under the

    imbedded ovum.

    2. Decidua Capsularis: the portion overlying the developing ovum; separates ovum from the rest of

    the uterine cavity; most prominent by 2nd month.

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    3. Decidua vera/ Desidua

    Parietalis: lines the remainder

    of the uterus

    Initially, the decidua capsularisand deciduas vera are

    separated by a space because

    the gestational sac does not fill

    the entire uterine cavity; by the

    fourth month, the growing sac

    fills uterine cavity.

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    4. Layers of deciduas Basalis and Decidua

    Vera

    a. Zona Compacta: uppermost/surface

    layer made up of compact cells.

    b. Zona Spongiosum: middle, spongy

    layer with glands and small blood vessels.

    c. Zona Basalis: lowest most/ basal layer

    * The zona basalis and zona spongiosumtogether form the functional layer zona

    functionales). Implantation is up to the

    level of spongiosum.

    * The zona basalis remains after

    delivery/ placental separation

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    5. Decidua Aging: Nitabuchs layer, a zone of

    fibrinoid degeneration, is where invading

    trophoblast meets the deciduas whenever the

    deciduas is defective.

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    C. PLACENTAL MATURITY: 12 weeks or 3

    months; functions most effectively through 40

    to 41 weeks; may be dysfunctional beyond 42

    weeks.

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    D. PLACENTAL FUNCTIONS: Varied

    1. Nutritive: transport nutrients and

    water soluble vitamins to fetus

    a. Fluid/gas transport

    * Diffusion: oxygen, carbon dioxide,

    water and electrolytes move from greater

    to lesser concentration

    * Facilitated transport: glucose

    * Active transport: amino acids,

    calcium, iron

    * Pinocytosis: fat, gamma globulin,

    albumin

    * Leakage allows fetal and maternal

    blood to mix slightly because of placental

    defect; normally there is no mixture of

    fetal blood.

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    2. Excretory with the amniotic fluid as

    the medium of excretion

    3. Respiratory organ of the fetus.

    4. The placental as a protective barriers

    to some substance and organism like

    heparin and bacteria; ineffective for

    virus, alcohol, nicotine, antibiotics,

    depressants and stimulants.

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    5. Endocrine: secretes hormones estrogen, progesterone, human

    chorionic gonadotropin (HCG), and human placental lactogen (HPL),

    also called chorionic somatomammotropin (HCS)

    a. Estrogen and progeterones major source of production after the first2 months is the placenta.

    b Human chorionic gonadotropin (HCG)

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    b. Human chorionic gonadotropin (HCG)

    * Secreted as early as 8 to 10 days after fertilization; detected in serum

    as early as the time of implantation by the most sensitive pregnancy test,

    the radioimmunoassay (RIA); and detected in urine by simple pregnancy

    test.

    * Functionc: prolong the life of the corpus luteum; serves as basis for

    pregnancy tests.

    * The hormone found elevated in excessive vomiting

    *Normal value: 400,00 I.U./24 hours

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    c. Human chorionic somatomammotropin (HCS) or Human Placental

    Lactogen (HPL)

    * Secreted by third week after ovulation

    * Influences somatic cellular growth of the fetus; resembles thegrowth hormone

    * The principal diabetogenic factor as it is the major insulin

    antagonist, or glucose sparing hormone

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    V. THE UMBILICAL CORD/FUNIS

    A. Length: 55cm, 1 inch across at term

    B. Parts:

    1. One left umbilical vein: carries oxygenated

    blood to the fetus

    2. Two umbilical arteries (left and right) carry

    deoxygenated blood from fetus to placenta

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    3. Whartons jelly, gelatinous

    substance

    a. Whartons Jelly: Specialized

    connective tissue, an extension of theamnion; surrounds the umbilical

    cord to prevent cord compression.

    b. The blood volume in the cord also

    helps prevent cord compression.

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    C. The cord extends from the fetal surface of the placental to the fetal

    umbilicus.

    D. Function: to transport oxygen and nutrients to the fetus and to returnmetabolic wastes including carbon dioxide from the fetus to the placenta.

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    VI. THE AMNIOTIC FLUID

    A. Clear, straw-colored fluid in w/c the fetus floats.

    B. Origin: Both fetal and maternal: amniotic epithelium maternal serum and in later

    part (10th week), fetal urine; constantly being replaced so there is no dry labor inpremature rupture of the bag of water.

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    C. Amount: 500 to 1,000 mL at term; polyhydramnios

    excessive amount of amniotic, greater than 1,000 to 1,500

    mL; oligohydramniosamount less than 300 to 500 mL.

    D. Reaction: neutral to alkaline (pH 7 to 7.25)

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    E. Abnormal Fluid Functions

    1. Serves as a protective

    cushion/shock absorber

    2. Separates fetus from

    membranes allowing

    symmetrical growth and free

    movement.

    3. Acts as a medium of excretion

    4. Serves as fetal drinks

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    5. Serves as a specimen forperiodic diagnostic exams todetermine fetal wellbeing orits absence.

    6. Maintains fetaltemperature

    7. Equalizes uterine pressure

    and prevents markedinterference with placentalcirculation during labor.

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    VII. STAGES OF INTRAUTERINE DEVELOPMENT

    A. The Ovum

    1. From fertilization to 2 weeks

    2. The period of pre-differentiation of organs.

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    3. When the ovum is exposed to a teratogen, the all or none

    law applies, meaning the ovum is damaged and is out in

    spontaneous abortion or it is not affected at all and continues

    to grow normally.

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    B. The Embryo

    1. From 2 weeks to 2 months

    2. The period of organ differentiation (organogenesis)

    3. Most Dangerous Period: A teratogen introduced at this stage may result

    in severe organ malformation and dysfunction.

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    C. The Fetus

    1. From 8 weeks to birth

    2. The period of post-

    differentiation of organs

    3. When exposed to a

    teratogen, a malformation is

    least likely to occur. If ever

    the fetus is affected, the

    effects will most likely be

    alteration in size or function

    but not in for.

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    VIII. THE EMBRYONIC

    GERM LAYERS

    A. Ectoderm: the outer layer;

    develops into:

    1. Nervous system.

    2. Hair Hair, nails, skin

    epidermis, sebaceous and sweat

    glands

    3. Salivary glands, mucous

    membrane of mouth

    4. Epithelium of nasal oral

    passage

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    B. Mesoderm: the middle l;ayer,

    develops into:

    1. Dermis

    2. Cardiovascular system

    3. Reproductive system system

    4. Musculo-skeletal system

    5. Urogenital system system, except the

    bladder

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    C. Endoderm/Entoderm: the

    inner layer develops into:

    1. Linings of gastrointestinaltract from pharynx to rectum]

    2. Liver, pancreas thyroid,

    parathyroid

    3. Respiratory tract

    4. Bladder, thyroid, thymus (for

    immunity building)

    IX FETAL CIRCULATION

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    IX. FETAL CIRCULATION

    A. Oxygenated blood from the

    placenta passes to the passes to the

    umbilical vein (1 left that contains

    the most amount of oxygenated

    blood at its entry into the liver);

    closes at birth with cord clamping

    and becomes ligamentum teres.

    From the umbilical vein, a smallamount of blood goes to the liver

    to nourish the liver. Most of the

    blood in the umbilical vein goes to

    the inferior vena cava thru the

    ductus which closes at birth w/cord clamping and becomes

    ligamementum venosum.

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    B. From the inferior vena

    cava, blood goes to the right

    auricle and is shunted to the

    left auricle by way of the

    foramen ovale, thus bypassing the lungs. It

    functionally closes with

    establishment of respiration

    about 1 to 3 days and

    anatomically closes a\in afew months.

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    C. From the left auricle, blood goes to the left ventricle to the

    aorta and to the lower parts of the body.

    D. From the hypogastric arteries, the right and left umbilicalarteries receive unoxygenated blood w/c is directed back to the

    placenbta for oxygenation and purification. The umbilical

    arteries close at birth with cord clamping and later become

    umbilical ligament.

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    E. Blood form the upper of thebody enters the heart by way ofthe superior vena cava (SVC).

    From the SVC, it goes to theright auricle, then to the rightventricle and to the pulmonaryartery.

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    F. From the pulmonary artery, asmall amount of blood goes to thelungs to nourish the lungs, butmost of the blood is shunted to

    the aorta by way of the ductusarteriosus. The ductus arteriosus,like the foramen ovale functionallycloses with establishment ofrespiration about 1 to 3 days and

    anatomically closes in a fewmonths about 2 to 3 monthsbecoming ligamentum arteriosum.If ductuc arteriosus fails to close,it will become an acyanotic heartdisease patent ductus arteriosus(PDA) - with machinery likemurmurs as an important sign.

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    X. INTRAUTERINE GROWTH AND DEVELOPMENT

    Age Development4 weeks All systems in the rudimentary form. Beginning formation of

    eyes, nose, GIT, Heart chambers formed; heart beating (14days) With arm and leg buds.

    8 weeks Head large in proportion to the body, Neuromusculardevelopment some movements, Rapid brain development,

    External genitalia appear12 weeks Placenta fully formed and functionging, Kidneys develop;

    secrete urine, Centers of ossification in most bones, With

    sucking and swallowing, Sex distinguishable, FHT detected

    by ultrasound16 weeks

    More human appearance, Quickening - mulltigravida,Meconium in bowels, External genitalia obvious, Scalp hair

    develops, Formed eyes, nose, ears, FHT by fetoscope20 weeks With vermix casecsa and downy lanugo, Quickening

    stronger, felt by primigrivida, FHT audible using

    stethoscope, Bones hardening

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    24 weeks Body-well proportioned, skin red and wrinkled, hearingestablished, eyebrows, eyelashes recognizable, When

    born, may breathe, but usually doesnt.28 weeks Viable; immature if born at this time, Surfactantproduction begins, Body is less wrinkled, With iron

    storage, Nails appear, Pupillary membrane has just

    disappeared from the eyes32 weeks Subcutaneous fats begins to deposit, Skin is smooth

    and pink, More reflexes present, With iron and calcium

    storage, Good chances of survival if delivered36 weeks Lecithin/ sphyngomyelin ration 2:1 (L/S), nails firm,

    With definite sleep/ wake pattern, Lanugo

    disappearing, Survival same as term40 weeks Fulterm with good muscle tone and reflexes, Little

    lanugo, If male, testes in scrotum, the age at time of

    EDC, With other characteristics features of the

    newborn.

    S C A CO C

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    XI. SPECIAL CONCERN:

    TERATOGENIC

    A. Teratogenesis: the dysgenesis of

    fetal organs as evidenced either

    structurally or functionally

    B. Manifestation: The typical

    manifestation of teratogenesis arerestricted growth or death of the

    fetus, carcinogenesis, and

    malformation, defined as defects in

    organ structure or function. These

    abnormalities vary in severity and

    major malformations may be life-threatening, or may have cosmetic

    functional effects and require

    major surgery.

    C S f Ri k B di i i k i

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    C. Safety Risk: Because any medication can present risks in

    pregnancy, and because not all risks are known, the safest

    pregnancy-related pharmacy is as little pharmacy as possible.

    Prescribing drugs for women during the antenatal and postnatal

    period is a balancing act and that no risk-free alternatives exist.Each drug should be assessed, and its risks and benefits should be

    weighed.

    D P l E

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    D. Paternal Exposure:

    Exposure to medications

    may alter the quality, size,

    shape performance, and

    production of sperm. Thisobservation suggests that

    drug exposure in the male

    may put the fetus at risk.

    Animal studies have shown

    that maternal teratogenicexposure may lead to

    pregnancy loss or failure of

    the embryo to develop, but

    no evidence shows that

    paternal exposure directly

    increases the risk of birth

    defects

    E Safety Guides Pregnancy

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    E. Safety Guides Pregnancy

    1. For any ailments seek medical attention. Take only prescribed drugs.

    2. D not self-medicate

    3. Do not take over-the-counter drugs including vitamins and minerals.

    4. Do not take alcohol no matter how slight. The US Federal Drug

    Administration (FDA), the government agency that oversees the sfatey of

    drugs, provides the most widely used system to grade the teratogenic effectsof medications. It assigns a safety category for medications using a 5-letter

    system: A, B, C, D and X.

    Drugs with Proven Terarogenic Effects

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    Drugs with Proven Terarogenic Effects

    Drugs Teratogenic EffectsAnticholinergic drugs Neonatal meconium ileusAntithyroid drugs (Prophylthiouracil, methimazole) Fetal & neonatal goiter, hypothyroidismCyclophosphamide CNS malformation, secondary cancerDiethylstilbestrol Vaginal cancer, other genitourinary defects in male

    or male offspringHypoglycemic drugs Neonatal hypoglycemiaMethotrexate

    CNS & limb malformation

    NSAIDs Constriction of ductus arteriosus, necrotizing

    enterocolitisPhenytoin Growth retardation, CNS defectsPsychoactive drugs (barbiturates, opiods,

    benzodiazepines)Neonatal withdrawal syndrome when given in late

    pregnancyTetracycline Teeth staining/ defects, bone defectsThalidomide Limb defects/ shortening, internal organ defectsWarfarin (Coumadin) Skeleton & CNS defects **Heparin is the

    anticoagulant of choice in pregnancy; does not


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