Development and Inheritance From fertilization to birth fertilization

Development and Inheritance • From fertilization to birth – fertilization – implantation – placental development – fetal development – gestation – labor – parturition (birth) Tortora & Grabowski 9/e 2000 JWS 1

Terminology of Development • Gestation period – time span from fertilization to birth (38 weeks) • Prenatal period (before birth) – embryological development • developing human for first 2 months after fertilization is known as an embryo • all principal adult organs are present – fetal development • from 9 weeks until birth is known as a fetus • by end of 3 rd month, placenta is functioning • Neonatal period is first 42 days after birth – obstetrics is branch of medicine that deals with the neonatal 2 period, pregnancy and labor Tortora & Grabowski 9/e 2000 JWS

From Fertilization to Implantation Tortora & Grabowski 9/e 2000 JWS 3

Events Before Fertilization • Haploid sperm nucleus & haploid secondary oocyte nucleus merge to form a single diploid nucleus • Occurs in uterine tube within 24 hours after ovulation (oocyte dies in 24 hours) • Events occurring before fertilization – peristalsis of uterine tube & movement of cilia transport the oocyte towards the uterus • oocyte releases chemical attractants – sperm swim towards oocyte by means of flagella • prostaglandins within the semen stimulate uterine contractions that help move sperm towards the oocyte – capacitation or final maturation of the sperm occurs within female • acrosomal membrane becomes fragile Tortora & Grabowski 9/e 2000 JWS 4

Sperm Contact during Fertilization • Sperm penetrates the granulosa cells around the oocyte (corona radiata) • Sperm digests its way through the zona pellucida – when ZP 3 glycoprotein binds to sperm head, it triggers the acrosomal reaction (enzyme release) • First sperm to fuse with oocyte membrane triggers the slow & the fast block to polyspermy – 1 -3 seconds after contact, oocyte membrane depolarizes & other cells can not fuse with it = fast block to polyspermy – depolarization triggers the intracellular release of Ca+2 causing the exocytosis of molecules hardening the entire zona pellucida = slow block to polyspermy 5 Tortora & Grabowski 9/e 2000 JWS

Events Within the Egg • Sperm entry, triggers oocyte to complete meiosis II and dump second polar body • Once inside the oocyte, the sperm loses its tail & becomes a male pronucleus • Fusion of male & female haploid pronuclei is the true moment of fertilization • Fertilized ovum (2 n) is called a zygote – zona pellucida still surrounds it Tortora & Grabowski 9/e 2000 JWS 6

Nature of Twins • Fraternal twins (dizygotic) – independent release of 2 oocytes fertilized by 2 separate sperm – as different as any 2 siblings • Identical twins (monozygotic) – 2 individuals that develop from a single fertilized ovum – genetically identical & always the same sex – if ovum does not completely separate, conjoined twins (share some body structures) Tortora & Grabowski 9/e 2000 JWS 7

Formation of the Morula • Rapid mitotic cell division of embryo is called cleavage • 1 st cleavage in 30 hours produces 2 blastomeres • 2 nd cleavage on 2 nd day • By 3 rd day has 16 cells • By day 4 has formed a solid ball of cells called a morula Tortora & Grabowski 9/e 2000 JWS 8

Development of the Blastocyst • A blastocyst is a hollow ball of cells that enters the uterine cavity by day 5 – outer covering of cells called the trophoblast – inner cell mass – fluid-filled cavity called the blastocele • Trophoblast & part of inner cell mass will develop into fetal portion of placenta • Most of inner cell mass will become embryo Tortora & Grabowski 9/e 2000 JWS 9

Implantation • Attachment of blastocyst to endometrium – occurs 6 days after fertilization – implants with inner cell mass in contact with the endometrium • Trophoblast develops 2 distinct layers – syncytiotrophoblast secretes enzymes that digest the endometrial cells – cytotrophoblast is distinct layer of cells that defines the original shape of the embryo • Trophoblast secretes human chorionic gonadotropin (h. CG) that helps the corpus luteum maintain the uterine lining 10 Tortora & Grabowski 9/e 2000 JWS

Implantation Notice: distinct syncytiotrophoblast and cytotrophoblast layers. Tortora & Grabowski 9/e 2000 JWS 11

Ectopic Pregnancy • Development of an embryo outside the uterus • Most often in uterine tube – common causes are blockages of uterine tube such as tumors or scars from pelvic inflammatory disease – symptoms are missed menstrual cycles, bleeding & acute pain • Twice as common in smokers because nicotine paralyzes the cilia Tortora & Grabowski 9/e 2000 JWS 12

Beginnings of Organ Systems(Gastrulation) • Day 8 – cytotrophoblast forms amnion & amnionic cavity • cells of inner cell mass on amnionic cavity form ectoderm • cells bordering on blastocele form endoderm – ectoderm & endoderm together form embryonic disk • Day 12 – endodermal cells divide to form a hollow sphere (yolk sac) – cytotrophoblast cells divide to fill the spaces surrounding the yolk sac with extraembryonic mesoderm • spaces develop in that layer to form future ventral body cavity Tortora & Grabowski 9/e 2000 JWS 13

Primary Germ Layers • Day 14 --cells of embryonic disc produce 3 distinct layers • endoderm forms epithelial lining of GI & respiratory • mesoderm forms muscle, bone & other connective tissues • ectoderm develops into epidermis of skin & nervous system Tortora & Grabowski 9/e 2000 JWS 14

Formation of Embryonic Membranes • Yolk sac – site of early blood formation – gives rise to gonadal stem cells (spermatogonia & oogonia) • Amnion – surrounds embryo with fluid: shock absorber, regulates body temperature & prevents adhesions – fluid is filtrate of mother’s blood + fetal urine – examine a sample of it for embryonic cells (amniocentesis) • Chorion – becomes the embryonic contribution to the placenta – derived from trophoblast & mesoderm lining it – gives rise to human chorionic gonadotropin (h. CG) • Allantois – outpocketing off yolk sac that becomes umbilical cord Tortora & Grabowski 9/e 2000 JWS 15

Amnion, Yolk sac, Chorion, allantois Tortora & Grabowski 9/e 2000 JWS 16

Placenta & Umbilical Cord • Placenta forms during 3 rd month – chorion of embryo & stratum functionalis layer of uterus • Chorionic villi extend into maternal blood filled intervillous spaces --- maternal & fetal blood vessels do not join & blood does not mix – diffusion of O 2, nutrients, wastes – stores nutrients & produces hormones – barrier to microorganisms, except some viruses • AIDS, measles, chickenpox, poliomyelitis, encephalitis – not a barrier to drugs such as alcohol • Placenta detaches from the uterus (afterbirth) Tortora & Grabowski 9/e 2000 JWS 17

Tortora & Grabowski 9/e 2000 JWS 18

Parts of Endometrial Lining • Decidua = all of endometrium lost as placenta – equals all of the endometrium, except stratum basalis • Decidua basalis---portion of endometrium deep to chorion • Decidua capsularis---part of endometrial wall that covers implanted embryo • Decidua parietalis---part of endometrial wall not modified by embryo until embryo bumps into it as it enlarges 19 Tortora & Grabowski 9/e 2000 JWS fuses with decidua parietalis • Decidua capsularis

Umbilical Cord • Contents – 2 arteries that carry blood to the placenta – 1 umbilical vein that carries oxygenated blood to the fetus – primitive connective tissue • Stub drops off in 2 weeks leaving a scar called the umbilicus Tortora & Grabowski 9/e 2000 JWS 20

Placenta Previa • Placenta is implanted near or covering os of cervix – occurs in 1 to 250 live births • May lead to spontaneous abortion, premature birth or increased maternal mortality • Major symptom is sudden, painless bright red vaginal bleeding in the 3 rd trimester • Cesarean section is preferred delivery method Tortora & Grabowski 9/e 2000 JWS 21

Fetal Ultrasonography • Transducer emits high-frequency sound waves – reflected sound waves converted to on-screen image called sonogram – patient needs full bladder • Used to determine fetal age, viability, growth, position, twins and maternal abnormalities Tortora & Grabowski 9/e 2000 JWS 22

Amniocentesis • Fetal cells from 10 ml sample of amniotic fluid examined for genetic defects • Test at 14 -16 weeks • Results back in one month • Needle through abdominal wall & uterus • Chance of spontaneous abortion is 0. 5% Tortora & Grabowski 9/e 2000 JWS 23

Chorionic Villi Sampling • As early as 8 weeks • Results in few days • Chance of spontaneous abortion 1 -2% • 30 mg of placenta removed by suction through cervix or with needle through abdomen • Chromosomal analysis reveals same results as amniocentesis Tortora & Grabowski 9/e 2000 JWS 24

Hormones of Pregnancy • Chorion – from day 8 until 4 months secretes h. CG which keeps corpus luteum active – corpus luteum produces progesterone & estrogen to maintain lining of uterus • Placenta – by 4 th month produces enough progesterone & estrogen that corpus luteum is no longer important – relaxin which relaxes CT of pelvis and cervix – human chorionic somatomammotropoin (h. CS) or human placental lactogen (h. PL) • maximum amount by 32 weeks • helps prepare mammary glands for lactation – corticotropin-releasing hormone (CRH) increases secretion of fetal cortisol (lung maturation) & acts to establish timing of birth 25 Tortora & Grabowski 9/e 2000 JWS

Hormone Blood Levels • Human chorionic gonadotropin (h. CG) produced by the chorion is less important after 4 months, because the placenta takes over the hormonal secretion of the corpus luteum. 26 Tortora & Grabowski 9/e 2000 JWS

Hormonal Secretion by the Placenta Tortora & Grabowski 9/e 2000 JWS 27

Early Pregnancy Tests • Detect human chorionic gonadotropin (h. CG) in the urine as soon as 8 days after fertilization – color change hen reaction between urine & antibodies in kit • False-negatives & false-positives do occur – excess protein or blood in urine – rare type of uterine cancer – steroid, diuretics, hormones and thyroid drugs alter test results Tortora & Grabowski 9/e 2000 JWS 28

Developmental Changes • Read Table 29. 2 to get a full description of the timing of fetal events during development Tortora & Grabowski 9/e 2000 JWS 29

Maternal Changes During Pregnancy Tortora & Grabowski 9/e 2000 JWS • Uterus nearly fills the abdominal cavity • GI tract compressed causing heartburn & constipation • Pressure on bladder causing changes in frequency & urgency • Compression of vena cava causing varicose veins & edema in the legs • Compression of renal vessels causing renal hypertension 30

Changes During Pregnancy • Cardiovascular changes to meet needs of fetus – rise in cardiac output of 20 -30% due to placenta – increase in heart rate 15% & increase in blood volume 30 -50% • Respiratory changes – increase in tidal volume 30% – decrease in expiratory reserve volume & airway resistance – minute respiratory volume increases as O 2 needs increase • Reproductive system changes – uterus increases in size from 80 g to 1200 g – hyperplasia and hypertrophy • Urinary system changes – increase in glomerular filtration rate of 40% Tortora & Grabowski 9/e 2000 JWS 31

Pregnancy-Induced Hypertension • Elevated blood pressure • Major cause is preeclampsia – sudden hypertension – large amounts of protein in the urine – generalized edema, blurred vision & headaches • Autoimmune or allergic reaction to presence of fetus • Eclampsia = convulsions & coma in mother Tortora & Grabowski 9/e 2000 JWS 32

Exercise and Pregnancy • In early pregnancy – avoid excessive exercise & heat buildup – linked to neural tube defects • Moderate exercise has beneficial effects – no evidence of inadequate blood flow to the placenta Tortora & Grabowski 9/e 2000 JWS 33

Labor and Parturition • Parturition means giving birth; labor is the process of expelling the fetus • Labor begins when progesterone’s inhibition is overcome by an increase in the levels of estrogen – progesterone inhibits uterine contraction – placenta stimulates fetal anterior pituitary which causes fetal adrenal gland to secrete DHEA – placenta converts DHEA to estrogen – estrogen overcomes progesterone and labor begins 34 Tortora & Grabowski 9/e 2000 JWS

Positive Feedback during Labor • Uterine contraction forces fetal head into cervix (stretch) • Nerve impulses reach hypothalamus causing release of oxytocin • Oxytocin causes more contractions producing more stretch of cervix & more nerve impulses Tortora & Grabowski 9/e 2000 JWS 35

True Versus False Labor • True labor begins when contractions occur at regular intervals – produces pain • back pain increases with walking – dilation of cervix with a discharge of bloodcontaining mucus in the cervical canal • False labor produces pain at irregular intervals but there is no cervical dilation Tortora & Grabowski 9/e 2000 JWS 36

Stages of Labor • Dilation – 6 to 12 hours – rupture of amniotic sac & dilation of cervix • Expulsion – 10 minutes to several hours – baby moves through birth canal • Placental – 30 minutes – afterbirth is expelled by muscular contractions Tortora & Grabowski 9/e 2000 JWS 37

Dystocia & Cesarean Section • Dystocia = difficult labor – due to fetal position or size – breech presentation is butt or feet first in birth canal • Cesarean section (C-section) – horizontal incision through lower abdominal wall and uterus – a history of multiple cesarean sections does not preclude a vaginal birth Tortora & Grabowski 9/e 2000 JWS 38

Adjustments of the Infant at Birth • Respiratory System – after cord is cut, increased CO 2 levels in blood cause muscular contractions and first breath – breathing rate begins at 45/minute for the first 2 weeks & declines to reach normal rate • Cardiovascular System – foramen ovale closes at moment of birth – ductus arteriosus & umbilical vein close down by muscle contractions & become ligaments – pulse rate slows down (120 to 160 at birth) – increase in rate of RBC & hemoglobin formation 39 Tortora & Grabowski 9/e 2000 JWS

Premature Infants • Preemie is any baby weighs less than 5 lb. 8 oz at birth • Causes – poor prenatal care – drug abuse – young or old mother (below 16 or above 35) • Below 36 weeks – respiratory distress syndrome due to insufficient surfactant is major problem Tortora & Grabowski 9/e 2000 JWS 40

Physiology of Lactation • Lactation = production & release of milk • Prolactin from anterior pituitary increases during pregnancy, but progesterone inhibits effects of prolactin until after delivery • After delivery, progesterone levels drop & suckling increases the release of prolactin & oxytocin (milk ejection reflex) • Colostrum = cloudy fluid released for few days • True milk produced by 4 th day 41 • Tortora If suckling stops, milk secretion stops & Grabowski 9/e 2000 JWS

Milk Ejection Reflex • Oxytocin cause release of milk into mammary ducts • Stimulation of touching nipple causes hypothalamus to release oxytocin • Oxytocin causes contraction of myoepithelial cells • Milk moved from alveoli into mammary ducts • Oxytocin release by other stimuli Tortora & Grabowski 9/e 2000 JWS – hearing a baby’s cry or touching the 42 genitals

Benefits of Breast-feeding • Faster & better absorption of the “right” nutrients • Beneficial cells – functional white blood cells • neutrophils help ingest bacteria in baby’s gut • macrophages produce lysozymes • plasma cells provides antibodies prevent gastroenteritis • Decreased incidence of diseases later in life – reduction in allergies, respiratory & GI infections, ear infections & diarrhea • Parent-child bonding • Infant in control of intake Tortora & Grabowski 9/e 2000 JWS 43

Nursing and Childbirth • Nursing of first-born twin speeds birth of second child – stimulates release of oxytocin • Nursing of only child – promotes expulsion of the placenta – helps control hemorrhage after birth – helps uterus return to normal size Tortora & Grabowski 9/e 2000 JWS 44

Inheritance • Passing of hereditary traits from one generation to the next • Genotype – all human cells contain 23 pairs of chromosomes • one chromosome in each pair came from the mother and the other came from the father • similar locations on each pair of chromosomes code for the same trait (alleles) – if one allele controls the express of a trait, it is the dominant allele – if the other allele is completely masked it is the recessive allele • a person with the same alleles on both chromosomes is said to be homozygous for the trait----heterozygous for the trait is having different alleles on homologous chromosomes – heterozygous individuals are carriers of a recessive gene Tortora & Grabowski 9/e 2000 JWS 45

Genotype & Phenotype • Genotype = your genetic makeup • Phenotype = what you look like (outward expression of your genes) • Punnett square – method of showing 4 possible genetic combinations in offspring of 2 individuals Tortora & Grabowski 9/e 2000 JWS 46

Genetic Problems • Error in meiosis called nondisjunction – chromosomes fail to separate properly – cell with one or more extra or missing chromosomes is called an aneuploid • (2 n-1) is missing a chromosome • (2 n+1) has an extra chromosome • Error in meiosis called translocation – location of chromosome segment is moved • crossing-over between 2 nonhomologous chromosomes • Down syndrome results from a portion of chromosome 21 becoming part of another chromosome – individuals have 3 copies of that part of chromosome 21 Tortora & Grabowski 9/e 2000 JWS 47

Incomplete Dominance • Neither member of an allelic pair is dominant over the other --- resulting phenotype is intermediate • Sickle-cell trait individuals have both Hb. A & Hb. S – suffer from only minor problems with anemia since have both normal & sickle-cell hemoglobin • Sickle-cell anemic individuals have 2 Hb. S alleles – produce sickle-cell hemoglobin – suffer from severe anemia Tortora & Grabowski 9/e 2000 JWS 48

Sickle-Cell Inheritance • 1 normal • 2 embryos will be sickle-cell trait • 1 sickle-cell anemia Tortora & Grabowski 9/e 2000 JWS 49

Multiple-Allele Inheritance – Genes with more than two alternate forms • 3 different alleles of the I gene • IA, IB, or i – A and B alleles are codominant since both genes are expressed equally – 6 possible genotypes produce 4 blood types • 4 phenotypes of the ABO blood groups are (A, B, AB & O) Tortora & Grabowski 9/e 2000 JWS 50

Polygenic Inheritance • Traits controlled by many genes – continuous gradations of small differences – body build, height and skin, hair & eye color • Skin color controlled by 3 genes (Aa, Bb, Cc) – person with genotype of AABBCC is dark – person aabbcc is light • Parental generation & F 1 and F 2 generation Tortora & Grabowski 9/e 2000 JWS 51

Autosomes & Sex Chromosomes • Each of us has a pair of sex chromosomes • Females XX • Males have XY – Y is smaller – Y is needed to produce male development Tortora & Grabowski 9/e 2000 JWS 52

Human Chromosomes • 22 pairs of autosomes • 1 pair of sex chromosomes Tortora & Grabowski 9/e 2000 JWS 53

Sex-Linked Inheritance • Genes found only on X chromosomes • Red-Green color blindness is lack of either red or green cones, so seen as same color – XCXC is normal, XCXc is carrier – Xc. Xc is color blind – XCY is normal, Xc. Y is color blind • Hemophilia is sex-linked trait where blood fails to clot • Other sex-linked traits – absence of incisors, night blindness, juvenile glaucoma, and some 54 types of deafness, diabetes, cataracts, and muscular dystrophy Tortora & Grabowski 9/e 2000 JWS

X-Chromosome Inactivation • Females have double dose of X chromosome in all cells • One X chromosome is randomly & permanently inactivated early in development • Visible as dark-staining Barr body easily seen in nucleus of neutrophils as “drumstick” – tightly coiled even in interphase cell Tortora & Grabowski 9/e 2000 JWS 55

Environmental Influences • Phenotype is result of environment effects on genetic makeup – more influential on polygenic traits such as height • Teratogens = cause developmental defects – Chemicals & Drugs • fetal alcohol syndrome = slow growth, facial features, defective heart & CNS • cocaine = attention problems, hyperirritability, seizures – Cigarette Smoking • low birth weight, cleft lip & palate, SIDS – Irradiation or radioisotopes during first trimester • mental retardation, microcephaly Tortora & Grabowski 9/e 2000 JWS 56

Infertility • Female – 10% of reproductive age U. S. population • ovarian disease or obstruction of uterine tubes • inadequate or excessive body fat • Male – definition is production of adequate quantities of viable, normal sperm & transport through ducts • seminiferous ducts sensitive to x-rays, infections, toxins, malnutrition & high scrotal temperatures Tortora & Grabowski 9/e 2000 JWS 57

Alternative Fertilization Techniques • Fertilization in a laboratory dish -- 16 cell stage placed into uterus – in vitro fertilization • mother given FSH to produce multiple oocytes (surgically removed) • mixed with solution containing sperm – intracytoplasmic sperm injection into oocyte • Embryo transfer – artificial insemination of oocyte donor – blastocyst transfer to infertile woman for pregnancy • Gamete intrafallopian transfer – FSH & LH stimulate multiple oocytes---aspiration & fertilization outside the body---reimplantation into uterine tubes (whole procedure is to skip vagina) Tortora & Grabowski 9/e 2000 JWS 58

Down Syndrome (DS) • Nondisjunction of chromosome 21 causes one of daughter cells to end up with extra copy – trisomy 21 ---2 copies from mom & one from dad • More common in older mothers – more exposure to radiation & chromosomedamaging chemicals • kinetochore microtubules that pull chromosomes apart sustain damage • 1 in 800 infants is born with Down syndrome – mental retardation, distinctive facial structures & malformation of the heart, ears, hands & feet Tortora & Grabowski 9/e 2000 JWS 59

Fragile X Syndrome • Defective gene on X chromosome – broken tip of X chromosome • Causes mental retardation in some of males with this gene – learning difficulties, oversized ears, enlarged testes & double jointedness – may be involved with autism • Unaffected males may pass gene onto daughters whose children may suffer Tortora & Grabowski 9/e 2000 JWS 60