• Fetus

conceptus from week 9 through birth

From Egg to Zygote

•Oocyte viable for 12 to 24 hours
•Sperm viable 24 to 48 hours after ejaculation
•For fertilization to occur, coitus must occur no more than
–Two days before ovulation
–24 hours after ovulation
•Fertilization - sperm's chromosomes combine with those of secondary oocyte to form fertilized egg (zygote)

Accomplishing Fertilization

•Ejaculated sperm
–Leak out of vagina immediately after deposition
–Destroyed by acidic vaginal environment
–Fail to make it through cervix
–Dispersed in uterine cavity or destroyed by phagocytes
–Few (100 to a few thousand) reach uterine tubes
•Sperm must become motile
•Sperm must be capacitated before they can penetrate oocyte
–Motility must be enhanced; membranes must become fragile to release hydrolytic enzymes
•Secretions of female tract weaken acrosome membrane
•Sperm follow "olfactory trail" to reach oocyte

Acrosomal Reaction and Sperm Penetration

•Sperm must breach oocyte coverings
–Corona radiata and zona pellucida
•Sperm weaves through corona radiata, then binds to zona pellucida and undergoes acrosomal reaction
–Enzymes released to digest holes in zona pellucida
–Hundreds of acrosomes release enzymes to digest zona pellucida
•Sperm head approaches oocyte
•Rear portion of acrosomal membrane binds to oocyte plasma membrane →
–Oocyte and sperm membranes fuse
–Gametes fuse as sperm's cytoplasmic contents enter oocyte
•Only one sperm allowed to penetrate oocyte (monospermy)

Block to Polyspermy

•Upon entry of sperm, Ca2+ surge from ER causes cortical reaction
–Cortical granules release enzymes (zonal inhibiting proteins, or ZIPs)
–ZIPs destroy sperm receptors
–Spilled fluid binds water and swells, detaching other sperm (slow block to polyspermy)

Completion of Meiosis II and Fertilization

•As sperm nucleus moves toward oocyte nucleus it swells to form male pronucleus
•The Ca2+ surge triggers completion of meiosis II → ovum + second polar body
•Ovum nucleus swells to become female pronucleus
•Fertilization – moment when membranes of two pronuclei rupture and chromosomes combine

Events of Embryonic Development: Zygote to Blastocyst Implantation

•Cleavage
–Occurs while zygote moves toward uterus
–Mitotic divisions of zygote
–First cleavage at 36 hours → two daughter cells (blastomeres)
–At 72 hours → morula (16 or more cells)
•At day 4 or 5, blastocyst (embryo of ~100 cells) reaches uterus

Implantation

•Blastocyst floats for 2–3 days
–Nourished by uterine secretions
•Implantation begins 6–7 days after ovulation
–Trophoblast cells adhere to site with proper receptors and chemical signals
–Inflammatory-like response occurs in endometrium
•Uterine blood vessels more permeable and leaky; inflammatory cells invade area
•Trophoblasts proliferate and form two distinct layers
–Cytotrophoblast (cellular trophoblast) - inner layer of cells
–Syncytiotrophoblast (syncytial trophoblast) - cells in outer layer lose plasma membranes, invade and digest endometrium
•Blastocyst burrows into lining surrounded by pool of leaked blood; endometrial cells cover and seal off implanted blastocyst
•Implantation completed by twelfth day after ovulation
–Menstruation must be prevented
–Corpus luteum maintained by hormone human chorionic gonadotropin (hCG)

Hormonal Changes During Pregnancy

•Human chorionic gonadotropin (hCG)
–Secreted by trophoblast cells; later chorion
–Prompts corpus luteum to continue secretion of progesterone and estrogen
–Promotes placental development via its autocrine growth factor activity
–hCG levels rise until end of second month, then decline as placenta begins to secrete progesterone and estrogen; low values at 4 months and rest of pregnancy

Placentation

•Formation of placenta from embryonic and maternal tissues:Temporary organ,Embryonic tissues
•Mesoderm cells develop from inner cell mass; line trophoblast
•Together these form chorion and chorionic villi
•Cores of chorionic villi invaded by new blood vessels; extend to embryo as umbilical arteries and vein
•Erosion → blood-filled lacunae (intervillous spaces) in stratum functionalis
•Villi lie in intervillous spaces, immersed in maternal blood
•Maternal portion of placenta –Decidua basalis
•Fetal portion of placenta–Chorionic villi
•Decidua capsularis - part of endometrium at uterine cavity face of implanted embryo
•Placenta fully formed and functional by end of third month–Nutritive, respiratory, excretory, endocrine functions
•Placenta also secretes human placental lactogen, human chorionic thyrotropin, and relaxin
•If placental hormones inadequate, pregnancy aborted
•Throughout pregnancy blood levels of estrogens and progesterone increase
•Prepare mammary glands for lactation
•Maternal and embryonic blood supplies normally do not intermix
•Embryonic placental barriers include:Membranes of chorionic villi,Endothelium of embryonic capillaries

Events of Embryonic Development: Gastrula to Fetus

• Germ Layers
– During implantation, blastocyst begins conversion to gastrula
• Inner cell mass develops into embryonic disc (subdivides into epiblast and hypoblast)
• Three primary germ layers form; extraembryonic membranes develop

Extraembryonic Membranes

• Amnion - epiblast cells form transparent sac filled with amniotic fluid
– Provides buoyant environment that protects embryo
– Helps maintain constant homeostatic temperature
– Allows freedom of movement; prevents parts from fusing together
– Amniotic fluid comes from maternal blood, and later, fetal urine
• Yolk sac - sac that hangs from ventral surface of embryo
– Forms part of digestive tube
– Source of earliest blood cells and blood vessels
• Allantois - small outpocketing at caudal end of yolk sac
– Structural base for umbilical cord
– Becomes part of urinary bladder
• Chorion - helps form placenta
– Encloses embryonic body and all other membranes

Gastrulation

•Occurs in week 3
•Embryonic disc → three-layered embryo with primary germ layers present
–Ectoderm, mesoderm, and endoderm
•Begins with appearance of primitive streak, raised dorsal groove; establishes longitudinal axis of embryo
•Cells begin to migrate into groove
–First cells form endoderm
–Cells that follow push laterally, forming mesoderm
•Notochord - rod of mesodermal cells that serves as axial support
–Cells that remain on embryo's dorsal surface form ectoderm
•Ectoderm, mesoderm, endoderm - primitive tissues from which all body organs derive
•Epithelia cells
–Ectoderm → nervous system; skin epidermis
–Endoderm → epithelial linings of digestive, respiratory, urogenital systems; associated glands
•Mesenchyme cells: Mesoderm → everything else

Organogenesis

• Gastrulation sets stage for organogenesis
– Formation of body organs and systems
• At eighth week
– All organ systems recognizable
– End of embryonic period
• Embryo begins as flat plate →
• Cylindrical body resembling three stacked sheets of paper folding laterally into tube, and at both ends

Specialization of Endoderm

•Primitive gut formed from endodermal folding
–Forms epithelial lining of GI tract
–Organs of GI tract become apparent, and oral and anal openings perforate
•Mucosal lining of respiratory tract forms from pharyngeal endoderm (foregut)
•Glands arise further along tract

Specialization of Ectoderm

•Neurulation
–First major event of organogenesis
–Gives rise to brain and spinal cord
–Induced by chemical signals from notochord
–Ectoderm over notochord thickens, forming neural plate
–Neural plate folds inward as neural groove with neural folds
•By 22nd day, neural folds fuse into neural tube
–Anterior end → brain; rest → spinal cord
•Neural crest cells migrate widely → cranial, spinal, and sympathetic ganglia and nerves; adrenal medulla; pigment cells of skin; contribute to some connective tissues
•Brain waves recorded by end of second month

Specialization of Mesoderm

•First evidence - appearance of notochord
–Eventually replaced by vertebral column
•Three mesoderm aggregates appear lateral to notochord
–Somites, intermediate mesoderm, and double sheets of lateral plate mesoderm
•Somites (40 pairs) each have three functional parts
–Sclerotome cells - produce vertebra and rib at each level
–Dermatome cells - form dermis of skin on dorsal part of body
–Myotome cells - form skeletal muscles of neck, trunk, and limbs (via limb buds)
•Intermediate mesoderm forms gonads and kidneys
•Lateral plate mesoderm consists of somatic and splanchnic mesoderm
•Somatic mesoderm forms:Dermis of skin in ventral region,Parietal serosa of ventral body cavity,Most tissues of limbs
•Splanchnic mesoderm forms:Heart and blood vessels,Most connective tissues of body,Entire wall of digestive & respiratory organs
•At end of embryonic period:Bones have begun to ossify; skeletal muscles well formed, contracting; metanephric kidneys developing; gonads formed,Lungs, digestive organs attaining final shape and body position,Blood delivery to/from placenta constant & efficient,Heart and liver bulge on ventral surface

Development of Fetal Circulation

•First blood cells arise in yolk sac
•By end of third week
–Embryo has system of paired vessels
–Two vessels forming heart have fused; bent into "S" shape
•Heart beats by 3½ weeks
•Unique vascular modifications
–Umbilical arteries and umbilical vein
–Three vascular shunts
•All occluded at birth
•Vascular shunts
–Ductus venosus - bypasses liver (umbilical vein → ductus venosus → IVC)
–Foramen ovale - opening in interatrial septum; bypasses pulmonary circulation
–Ductus arteriosus - bypasses pulmonary circulation (pulmonary trunk → ductus arteriosus → aorta)

Events of Fetal Development

•Fetal period - weeks 9 through 38
•Time of rapid growth of body structures established in embryo

Effects of Pregnancy on the Mother: Anatomical Changes

•Reproductive organs become engorged with blood
–Chadwick's sign - vagina develops purplish hue
–Breasts enlarge and areolae darken
–Pigmentation of facial skin many increase (chloasma)
•Uterus expands, occupying most of abdominal cavity
–Ribs flare → thorax widens
•Lordosis occurs with change in center of gravity
•Relaxin causes pelvic ligaments and pubic symphysis to relax to ease birth passage
•Weight gain of ~13 kg (28 lb)
•Good nutrition vital
–300 additional daily calories
•Multivitamins with folic acid reduce fetal risk of neurological problems, e.g., spina bifida, anencephaly, and spontaneous preterm birth

Effects of Pregnancy: Metabolic Changes

•Placental hormones
–Human placental lactogen (hPL) (human chorionic somatomammotropin (hCS))
•→ maturation of breasts, fetal growth, and glucose sparing in mother (reserving glucose for fetus)
•Parathyroid hormone and vitamin D levels high throughout pregnancy → adequate calcium for fetal bone mineralization

Effects of Pregnancy: Physiological Changes

•GI tract:Morning sickness believed due to elevated levels of hCG, estrogen and progesterone,Heartburn and constipation are common
•Urinary system:↑ Urine production due to ↑ maternal metabolism and fetal wastes, Frequent, urgent urination; stress incontinence may occur as bladder compressed
•Respiratory system:Estrogens may cause nasal edema and congestion,Tidal volume increases,Dyspnea (difficult breathing) may occur later in pregnancy
•Cardiovascular system:Blood volume increases 25–40%
•Safeguards against blood loss during childbirth:Cardiac output rises as much as 35-40%
•Propels greater volume around body:Venous return from lower limbs may be impaired, resulting in varicose veins

Homeostatic Imbalance

•Preeclampsia
–Insufficient placental blood supply → fetus starved of oxygen
–Woman → edematous, hypertensive, proteinuria
–May be due to immunological abnormalities
•Correlated with number of fetal cells that enter maternal circulation

Parturition

•Giving birth to baby
•Labor
–Events that expel infant from uterus
•Increased production of surfactant protein A (SP-A) in weeks before delivery may trigger inflammatory response in cervix → softening in preparation for labor

Initiation of Labor

•Fetus determines own birth date
•During last few weeks of pregnancy:Fetal secretion of cortisol stimulates placenta to secrete more estrogen
•Causes production of oxytocin receptors by myometrium
•Causes formation of gap junctions between uterine smooth muscle cells
•Antagonizes calming effects of progesterone, leading to Braxton Hicks contractions in uterus
•Fetal oxytocin causes placenta to produce prostaglandins
•Oxytocin and prostaglandins - powerful uterine muscle stimulants:Due especially to prostaglandins, contractions → more frequent and vigorous,Anti-prostaglandins contraindicated during labor
•Increasing cervical distension:Activates hypothalamus, causing oxytocin release from posterior pituitary,Positive feedback mechanism occurs
•Greater distension of cervix → more oxytocin release → greater contractile force → greater distension of cervix → etc.

Stages of Labor: Dilation Stage

•From labor's onset to fully dilated cervix (10 cm)
•Longest stage of labor - 6–12 hours or more
•Initial weak contractions:
•15–30 minutes apart, 10–30 seconds long
•Become more vigorous and rapid
•Cervix effaces and dilates fully to 10 cm
•Amnion ruptures, releasing amniotic fluid
•Engagement occurs - head enters true pelvis

Stages of Labor: Expulsion Stage

•From full dilation to delivery of infant
•Strong contractions every 2–3 minutes, about 1 minute long
•Urge to push increases (in absence of local anesthesia)
•Crowning occurs when largest dimension of head distends vulva:Episiotomy may be done to reduce tearing

Stages of Labor: Expulsion Stage

•Vertex position – head-first:Skull dilates cervix; early suctioning allows breathing prior to complete delivery
•Breech position – buttock-first:Delivery more difficult; often forceps required, or C-section (delivery through abdominal and uterine wall incision)

Stages of Labor: Placental Stage

•Strong contractions continue, causing detachment of placenta and compression of uterine blood vessels
–Limit bleeding; cause placental detachment
•Delivery of afterbirth (placenta and membranes) occurs ~30 minutes after birth
•All placenta fragments must be removed to prevent postpartum bleeding

Adjustments of the Infant to Extrauterine Life

•Neonatal period - four-week period immediately after birth

First Breath:
•↑ CO2 → central acidosis → stimulates respiratory control centers to trigger first inspiration
–Requires tremendous effort – airways tiny; lungs collapsed
–Surfactant in alveolar fluid helps reduce surface tension
•Respiratory rate ~45 per minute first two weeks, then declines
•Keeping lungs inflated difficult for premature infant(< 2500 g, or 5.5 pounds, at birth)
–Surfactant production in last months of prenatal life
–Preemies usually on respiratory assistance until lungs mature

Transitional Period

•Unstable period lasting 6–8 hours after birth
–Alternating periods of activity and sleep
–Vital signs may be irregular during activity
–Baby gags frequently as regurgitates mucus and debris
•Stabilizes with waking periods occurring every 3–4 hours

Occlusion of Fetal Blood Vessels

•Umbilical arteries and vein constrict and become fibrosed
•Proximal umbilical arteries → superior vesical arteries to urinary bladder
•Distal umbilical arteries → medial umbilical ligaments
•Umbilical vein becomes round ligament of liver (ligamentum teres)
•Ductus venosus → ligamentum venosum about 30 minutes after birth
•Pressure changes from infant breathing cause pulmonary shunts to close:Foramen ovale → fossa ovalis up to a year after birth,Ductus arteriosus → ligamentum arteriosum about 30 minutes after birth

Lactation

•Production of milk by mammary glands
•Toward end of pregnancy:Placental estrogens, progesterone, and human placental lactogen stimulate hypothalamus to release prolactin-releasing factors (PRFs) → Anterior pituitary releases prolactin
•2-3 days later true milk production begins
•Colostrum:Less lactose but more protein, vitamin A, minerals than true milk; almost no fat,Yellowish secretion rich in IgA antibodies
•IgA resistant to digestion; may protect infant against bacterial infection; absorbed into bloodstream for immunity:Released first 2–3 days,Followed by true milk production
•Prolactin release wanes after birth
•Lactation sustained by mechanical stimulation of nipples - suckling-Suckling causes afferent impulses to hypothalamus → prolactin → stimulates milk production for next feeding
–Hypothalamus also → oxytocin from posterior pituitary → let-down reflex

Advantages of Breast Milk

•Fats and iron better absorbed; amino acids more easily metabolized, compared with cow's milk
•Beneficial chemicals:IgA, complement, lysozyme, interferon, and lactoperoxidase (protect from infections),Interleukins and prostaglandins prevent overzealous inflammatory responses,Glycoprotein deters ulcer-causing bacterium from attaching to stomach mucosa
•Natural laxative effect helps eliminate bile-rich meconium, helping to prevent physiological jaundice
•Encourages bacterial colonization of large intestine
•Women nursing 6 months lose bone calcium; replaced after weaning if healthy diet
•Women may ovulate when nursing despite inhibition of GnRH and gonadotropins

Assisted Reproductive Technology

•Surgical removal of oocytes following hormone stimulation
•Fertilization of oocytes
•Return of fertilized oocytes to woman's body
•Disadvantages:Costly, emotionally draining, painful for oocyte donor
•In vitro fertilization (IVF):Oocytes and sperm incubated in culture dishes for several days,Embryos (two-cell to blastocyst stage) transferred to uterus for possible implantation
•Zygote intrafallopian transfer (ZIFT):Fertilized oocytes transferred to uterine tubes
•Gamete intrafallopian transfer (GIFT):Sperm and harvested oocytes are transferred together into the uterine tubes
•Cloning:Legal, moral, ethical, political roadblocks