Pregnancy 13

• divides mitotically to form twodaughter cells called blastomeres
• •Mitotic cell division proceeds and cell typedifferentiation emerges

the process of cellmovements by which a developing embryoforms distinct germ layers from theembryonic disc that later grow intoparticular organs

developing organism between betweenfertilization and complete implantation;implantation is initiated at approximately 7 daysafter fertilization (can be initiated as late as 10days after fertilization); implantation is completeby end of 2nd week

prenatal stage between completion of implantation at end of 2nd week through 8th week after fertilization

prenatal stage between 9th week after fertilization until birth

Average time of 38 weeks (266 days) fromfertilization/conception to birth and is divided into 3 trimesters each around 3 months long

• • Gestational age definition in clinical medicine:
• duration since day 1 of last menstrual periodwhich is approximately 2 weeks longer than duration since conception
• • Gestational age in clinical medicine:
• averagegestational age of a term birth is 40 weeks (280days)

• • Biological definition:
• conception
• • Clinical medicine definition:
• day 1 oflast menstrual period, which is onaverage two weeks before conception
• • General public definition:
• 1-2 daysafter a missed menstrual period or when the pregnancy test is positive,which is on average two weeks after conception (when hCG is detectable)

• • Missed menstrual period with coitus in thepast month
• • Nausea in morning (“morning sickness”)
• • Increase in size and tenderness of breasts
• • Darkening of areola around nipples

• • Increase in size of abdomen
• • Missed consecutive menstrual cycles
• •Increase in frequency of urination
• • Positive Hegar’s sign:
• uterine cervix becomes softer by 6th week of pregnancy
• • Positive pregnancy test

• • Detection of fetal heartbeat
• • Feeling the fetal movement
• •Visualization of fetus by ultrasound or fetoscopy

• • Human chorionic gonadotropin (hCG) hormone is produced by blastocyst and placenta of embryo and fetus
• • hCG has similar biological activity as LH
• • Detection of human chorionic gonadotropin (hCG)hormone present in blood and urine indicates pregnancy
• • Most urine and blood tests are not able to detect hCG until 15 days after conception or one day after missed menses
• • Can have false positive or false negative tests

• • After fertilization the zygote undergoes several mitotic divisions to become morula,which is a ball of 16 to 32 cells, by 3rd day after fertilization
• • The preembryo continues to divide as it passes down the oviduct to the uterotubaljunction
• • Movement of the developing preembryo is facilitated by the beating of oviductal cilia in the uterine direction
• •3-4 days after fertilization the preembryo enters the uterus

• the preembryoenters the uterus and is a mass of cells called the blastocyst
• • Blastocyst: ball made of single outer layer of cells (trophoblast) just inside the zona pellucida surrounding a fluid-filled cavity called the blastocoel
• • Inner cell mass in blastocyst: clump of cells near one end of blastocyst underneath the trophoblast layer
• • Inner cell mass gives rise to the embryo and also is the source of embryonic stem cells

• • Conception usually occurs in ampullary-isthmic portion of the oviduct
• •Dividing ball of cells moves through theoviduct to the uterus where implantation is initiated approximately7 days after conception

• • Implantation requires a uterus that hasbeen primed with appropriate amounts of estradiol and progesterone at the right time
• • Corpus luteum secretes modest levels of estrogen and high levels of progesterone which primes the uterus and makes the endometrium more vascular, secretory, and ready for implantation
• • Progesterone also causes the uterus to secrete protease enzyme that dissolves the zona pellucida surrounding the blastocyst

• • A non-implanted blastocyst rests freely in the uterine cavity for 2-3days
• • On approximately day 6 afterconception, the uterus secretes a protease enzyme that dissolves the zona pellucida

• • When zona pellucida is completely dissolved, the inner cell mass end of the blastocyst attaches to the uterine wall and penetrates the endometrium (=implantation initiation) approximately 7days after fertilization
• • A blastocyst poised for implantation releases signaling molecules that interact with endometrium and allow the process to proceed normally

• • In early phase of implantation, the trophoblast differentiates into an outer syncytiotrophoblast and an innercytotrophoblast
• •Syncytiotrophoblast secretes proteases that breakdown cells of the uterine endometrium
• • Cells of uterine stroma demonstrate adeciduoma response and multiply rapidly and form a cap over blastocyst which makes implantation complete

• • Trophoblast/ syncytiotrophoblast penetrates epithelium and then stroma
• • Blastocyst penetrates further into stroma and amniotic cavity appears and blastocoel becomes yolk sac cavity
• • Deciduoma response: uterine tissue grows around and over blastocyst and implantation is complete
• • Sinusoids full of maternal blood developwithin the syncytiotrophoblast

• • Day 0: conception with zygote formation
• • Day 1: two blastomere cells
• •Day 3: morula (16-32 cells)
• • Day 4: early blastocyst
• • Day 5: late blastocyst
• • Day 6: blastocyst attaches to endometrium
• • Day 7: implantation begins (may begin on day 10)
• • Day 8: amniotic cavity & embryonic disc form
• • Day 9: uterine sinusoids develop
• • Day 10: implantation complete
• • Day 15: first missed menses/positive pregnancy test

• • Fetal cells are genetically different than those of the mother since half of the chromosomes come from the father of the fetus.
• • However, the common histocompatability molecules (HLAs)found on most nucleated cells
• are NOT found on placental cells.
• • This may be part of the reason why implantations are not routinely rejected by the mother’s tissue.

• • Soon after implantation the inner cell mass differentiates into the bilaminar embryonic disc which consists of two layers of cells, the epiblast and hypoblast
• • Hypoblast, along with epiblast and trophoblast,contribute to development of extraembryonic membranes which sustain embryo during intrauterine development
• • Only epiblast layer gives rise to embryo proper
• • Epiblast splits into 3 germ layers:
• ectoderm,mesoderm, endoderm

• • While the innate immune system can protect against infections it can also contribute to the fetal-maternal immune adjustment and the establishment of an adequate micro environment that will promote cell growth and inhibit harmful inflammatory immune reactions.
• • Successful implantation is known to be associated with a local Th1 (proinflammatorycytokine) response and issubsequently controlled by Th2 (antiinflammatorycytokine) response.

• • During implantation, apoptosis is critical for appropriate tissue remodeling of maternal decidua tissue and invasion of developing embryo.
• • Macrophages actively clear apoptotic cellsin the placental bed around developing embryo & fetus.
• • Macrophages are also an important source of cytokines and growth factors and it is postulated that these cells contribute to maintaining the appropriate balance of Th-1and Th-2 cytokines in the placental bed.

• • Thus, an appropriate balance between pro inflammatory and anti-inflammatorycytokines is thought to be essential for determining the success or failure of implantation and pregnancy.
• • At the site of implantation RANTES(regulated upon activation, normal T cell expressed
• and secreted) promotes trophoblast cell survival and modulates the balance of T reg/T effector lymphocytes in favor of maternal tolerance.

• Trophoblast cells can express Toll LikeReceptors which allow the placenta to recognize and respond to any microorganism that may endanger the fetus.

• • Nervous system
• • Epidermis of skin, hair, nails, and toothenamel

• • Skeleton
• • Notochord that develops into vertebral column
• • Muscles
• • Heart & circulatory system
• • Kidneys
• • Gonads
• • Deep layers of skin

• • Digestive tube and the liver, gallbladder, and pancreas that bud off the gut tube
• • Respiratory tube including the lungs

• • Yolk sac (mainly vestigial in humans)
• • Allantois (mainly vestigial in humans)
• • Amnion 4th membrane is the chorion and is derived from cytotrophoblast

• • Endoderm-lined membrane that surrounds the blastocoel (yolk saccavity)
• •Vestigial & non-functional in humansbut is very important in birds that lay eggs
• • Degenerates early in embryonic development in humans

• • Grows over forming embryo
• • Amniotic cavity becomes filled with amniotic fluid
• • Amniotic fluid supports and protects the fetus against mechanical shock and provides water and other materials to fetus

• • 8 weeks: 5-10 ml
• • 20 weeks: 250 ml
• • 38 weeks: 1000-1500 ml
• • 40 weeks/term: 500-1000 ml
• • Amniotic fluid is secreted and absorbed at a maximal rate of 300-600 ml per hour

• • Derived from the cytotrophoblast and surrounds the embryo after 1 month of development
• • Chorion eventually fuses with amnion
• • Chorion forms an important component of the placenta

• • Placenta serves as a nutrient, respiratory, andexcretory organ for fetus
• • Through placenta fetus receives oxygen, glucose,growth factors, and other nutrients and eliminates carbon dioxide and other waste products
• • Molecules larger than 500 molecular weight will not pass through the chorionic villi and into fetal blood vessels
• • However, late in pregnancy, large protein maternal antibodies are actively pumped into fetal circulation by placental cells

• Human placenta is hemochorial because the chorionic villi are directly bathed by maternal blood

• • Around day 14 after conception, finger like projections (chorionic villi) of the cytotrophoblast extend through the syncytiotrophoblast and toward the vascular uterine stroma
• • Sinusoid pools of maternal blood bath chorionic villi

• • Contents of maternal blood (e.g., glucoseand oxygen) diffuse from uterine sinusoids through the thin wall of each chorionic villus and into the fetal vessel within each villus and travel to the fetus via the umbilical vein
• • In the opposite direction, the fetal waste products (e.g., CO2) leave the fetal blood via the umbilical arteries and diffuse across villi into mother’s blood to be excreted

• • Week 4: 20% of inner uterine wall covered by placenta
• • Week 20: 50% of inner uterine wall covered by placenta which weighs 200gm, while fetus
• weighs 500 grams
• • Week 40: placenta weight is 700 gmsand has 285 liters of blood that passthrough it each day

• • As fetus and placenta grow, the stratum functionalis of endometrium is transformed into the “decidua” of the pregnant uterus
• • Decidua basilis: maternal part of placenta
• • Decidua capsularis: result of deciduoma response with overgrowth of endometrium
• • Decidua parentalis: endometrium notdirectly connected to fetus
• • Technically the fetus resides within theuterine wall, not in the uterine cavity

• • Connects fetus with the placenta
• • Derived from body stalk that is structure connecting embryo and chorion
• • At birth, cord is 0.3-1.0 inches diameter and 20-22 inches long and is covered with amniotic membrane
• • Two umbilical arteries carry de-oxygenated fetal blood to the placenta
• • One umbilical vein carries oxygenated blood from the placenta to the fetus
• •Vessels within cord are cushioned by a gelatinous substance called Wharton’s jelly

• • Implant close together: single placenta, fusedchorions, and two amnions.
• Monozygotic identical twins: develops when inner cell mass of blastocyst divides, producing two embryos with a single placenta and chorion,but two amniotic sacs.
• • In some cases, however, splitting of early morula produces monozygotic twins with separate amnions, chorions, & separate or fused placentas

• • Dizygotic twin frequency varies by ethnicity,heredity, maternal age, parity, and fertility drugs:
• • Ethnic differences appear to be in part due to ethnic variations in follicle-stimulating hormone
• • 1/20 in a rural community of Yoruba in Nigeria
• • 1/80 in black females
• • 1/100 in white females
• • 1/155 in Japan

• • Heredity of mother is more important than father
• • Rate of twinning is near 0% at puberty to a peak level at around age 37 when FSH levels are
• highest
• • Rate of twinning increases with parity: the more children awoman has had the greater the likelihood her next pregnancy will be twins
• • Increased fecundity and higher rate of dizygous twins reported in women who conceive within one month afterstopping oral contraceptives, but not during subsequentmonths; this appears to be due to the sudden release of pituitary gonadotropin in amounts greater than usual during the first spontaneous cycle after stopping oral contraceptives.
• • Use of fertility enhancing drugs e.g., clomid increase therate dizygotic, trizygotic, etc. pregnancies

• Monozygotic twin frequency worldwide is around 1/250 and is largely independent of ethnicity, age, heredity,and parity

• • Delayed transport through the fallopian tube
• • Women who have recently been oncombination oral contraceptives because they cause decreased tubal
• motility• Minor trauma to blastocys during assisted reproductive techniques

• • If division occurs in first 72 hours after conception, before chorion and morula formation, two embryos with twochorions, two amnions, and one or two placentas will develop
• • If division occurs between days 4-8 after conception, after chorion and inner cell mass formation, two embryos with one chorion, two amnions, and one placenta will develop
• • If division occurs after day 8, after chorion and amnion have already formed, two embryos with a single chorion,amnion, and placenta will develop
• • If division occurs even later e.g., day 14, that is after the chorion, amnion, and embryonic disk have been formed,cleavage is incomplete and conjoined twins are formed

• • By end of second week post-conception, thepreembryo develops into a flattened embryotic disc consisting of three germ layers:
• ectoderm,mesoderm, and endoderm
• • Week 3-8 is embryonic period during which time all major internal and external structures takeshape
• • Very sensitive to disturbances (teratogens,mutagens) that could result in death or congenital malformations

• • Week 3 of development, the flat, trilaminarembryonic disc begins to curl under to form asausage-like shape
• • Ectoderm forms dermal layer & nervous system
• • Endoderm lines the inner tube which formsgut/intestine
• • Mesoderm is sandwiched in between these layers
• •Neural tube develops along embryo back and develops spinal cord and brain from ectoderm
• • A series of lumps (somites) form along either side of neural tube which develop into the vertebrae,ribs, and muscles in the back

• • 2 mm long embryo with C shape at beginning of week 4
• • Eyes began to form on head
• • Inner ear development begins
• • Pharyngeal arches develop in neck area which will develop into jaws, ear and other structure
• • Heart forms and begins beating
• • Tiny arm and leg buds develop

• • Rapid growth of brain
• • Arm buds flatten and handsbecome paddle shaped
• • 1 cm in length by end of week

• • Eyes become pigmented
• • Exterior ears began to form
• • Head/brain continues to grow
• • Leg bud becomes paddle shaped
• • Hand rays indicate positions of digits
• • Distinct tail is still present

• • Toe rays form indicating position ofdigits
• • Rapid development of gut tube causes intestines to protrude into the umbilical cord to produce an umbilical herniation
• • Tail is diminished

• • 1.25 inches long by the end of week 8
• • Eyelids have grown to meet each other and fuse so eyes are closed
• • Fingers and toes can be clearly seen,however, a thin sheet of webbing still exists between each digit
• • Tail has disappeared
• • Embryo now begins to look human
• •Brain, spinal cord, and peripheral nerves areall developed

• • Organ systems established in the embryonic period continue to develop and differentiate
• • Period of rapid growth

• • fetal heart rate can be heard with astethoscope
• • Fetus can react to stimuli and fetal movements begin, however mom can not yet feel these movements Month 4-5 gestation
• • Mom may began to feel fetus moving

• • Skin covered with protective layer of fatty secretions called vernix caseosa
• • Skin grows layer of downy hair (lanugo)

• • Fetus adds layers of fat and loses its wrinkled appearance
• • Lungs mature

• • The limiting factor for survival of premature infants is lung development
• • Youngest premature infants that have survived have been a biological gestation age of 21 weeks postconception (clinical medicine gestational age of 23 weeks) and less than 400 grams in weight;
• most born atthis age and size do not survive.

• • Fetus derives nutrients from Mother’sblood via the umbilical vein in form of glucose, amino acids, fatty acids,vitamins, salts, and minerals
• • Carbon dioxide & other wasteproducts are delivered to placenta by umbilical arteries

• • Fetal kidneys are functionalthroughout fetal period and produce 450 ml of urine a day late inpregnancy which is excreted into amniotic fluid
• • In late pregnancy, the fetus swallows about

• • The placenta is oxygenating unit for fetus
• • When blood enters the right side of the fetal heart, it travels up the pulmonary trunk and by passes
• the lungs by moving through the ductus arteriosis to the aorta

• • The deoxygenated blood reaches the placenta via the umbilical arteries,where it releases carbon dioxide andpicks up oxygen
• • Oxygenated blood travels in umbilical vein back to the right side of the fetal heart

• • The blood is exchanged between theright side and left side of heart through passage of blood through hole called foramen ovale between right & left atria
• • Blood is transported from the right ventricle directly to the aorta via theductus arteriosis
• • The ductus arteriosis and the for amenovale both typically close at birth

• • 50% of preembryos/embryos die within the firstthree weeks of life
• • Conceptus is typically lost before the womenknows that she is pregnant
• • Of confirmed pregnancies, 15-20% miscarry
• • Chromosomal abnormalities account for 42% of spontaneously aborted
• preembryos/embryos/fetuses
• • Chromosomal abnormalities occur in 1/200 newborns

• Viruses:
• • HIV, chickenpox, herpes simplex,mumps, rubella, parvovirus
• Bacteria:
• • Syphilis, tuberculosis, typhoid

• • Main effects during 4-7th week gestation
• • Mercury, lead, cadmium, arsenic, PCBs,DDT, benzene, and carbon tetrachloride
• • Alcohol/fetal alcohol syndrome
• • Tobacco
• • Recreational intoxicants
• • Some pharmaceuticals

• • Ultrasound can detect fetal heart rate by 8 weeks
• • Ultrasound is used to assess fetal anatomy and movement and placenta position
• • Multiple serum marker test from maternal blood:
• hCG (human chorionicgonadotropin), alpha-fetoprotein, and estriol levels can estimate likelihood that a fetus has Down’s syndrome, however this test is not definitive

• • Recommended in women over 34 years, or women with family history of genetic disorders
• • Procedure performed between 14th and16th week of pregnancy (biologicaldefinition) or 16-18 weeks gestation (clinical medicine definition)
• • Needle is inserted through abdominal and uterine walls into amniotic fluid with ultrasound guidance
• • Cells and amniotic fluid can be evaluated for chromosomal abnormalities

• • Recommended in women over 34 years, or women with family history of genetic disorders
• • Procedure performed between 8th & 10th week of pregnancy (biological definition) or 10th & 12th week gestation (clinical medicine definition)
• • Needle is inserted through vagina and cervix into uterine cavity using ultrasound as a guide
• • Chorionic cells removed from placenta & analyzed
• • Higher risk of inducing miss-carriage than with amniocentesis
• • With CVS get results earlier than amniocentesis, which is preferable if the pregnancy is going to be terminated based on the test results

• • Relatively safe for mother
• • 87% of all induced abortions in the USA are in the 1st trimester
• • Medical abortion from taking pill or surgical abortion that uses aspiration and instruments to empty contents of uterus

• • Mifepristone = RU486 referred as the abortion pill acts by preventing progesterone action byblocking progesterone receptors
• • Mifepristone can be taken within first 35 dayspost-conception to induce a miscarriage and
• is sometimes taken with misoprostol (prostaglandin)vaginal suppository that softens the cervix tofacilitate the release of miscarriage out of cervix

• • Most frequent used method in 1st trimesterabortion in USA
• • Done in 5th - 11th week after conception
• • Vacurette tube is placed through cervix intouterus and is connected to a suction devise
• • If material is not completely removed bysuction, the endometrium is scraped with acurette

• • Done in 8th - 14th week afterconception
• • Cervix is typically dilated withLaminaria which is a brown algae
• • The endometrium is scraped with acurette which is inserted through the cervix

• • Cervix is typically dilated with a small tube of Laminaria (brown algae)inserted into cervix which absorbsmoisture and expands and dilates cervix
• • Administration of intra-amniotic (Fig15-7) saline, urea, glucose, or prostaglandin alone or in combination to terminate the pregnancy and induce delivery

• • Performed after 12th week postconception
• • Cervical dilation using Laminaria(brown algae)
• • Uterine contents removed usingsuction, curettes,and forceps

• • Dilation and extraction referred to as“partial birth abortion” and has been typically performed in the late 2nd trimester and early 3rd trimester
• • Ban on this procedure in certain areas of the world