Development and Inheritance - Lecture Notes

Prenatal Period

• Begins with fertilization

• Secondary oocyte and sperm unite

• Ends 38 weeks later with birth

  • Pre-embryonic period

  • Embryonic period

  • Fetal period

Pre-embryonic Period

• First 2 weeks after fertilization

• Zygote, cell produced by fertilization, becomes spherical multicellular structure blastocyst

• Ends with blastocyst implants in uterine lining

Embryonic Period

• 3^rd through 8^th weeks of development

• Rudimentary versions of major organs appears

• Now called an embryo

Fetal Period

• Remaining 30 weeks prior to birth (9-38 weeks)

• Organism is now called a fetus

• Continues to grow and increase in complexity

Embryogensis

Developmental period of pre-embryonic and embryonic periods

Fertilization

• Fusion of sperm and secondary oocyte

• Restores diploid number of chromosomes (46 total)

• Determines the sex of the organism

• Occurs in the ampulla of the uterine tube

Capacitation

• Physiology condition undergone by sperm to become capable of fertilizing the secondary oocyte

• Occurs in female reproductive tract

• Glycoprotein coat and some proteins

  • Removed from sperm plasma membrane

• Lasts several hours

Influx of Ca²⁺

• Oocyte in surrounded by the cumulus oophorus (bound by pogesterone)

• Necessary for capacitation, acrosome reaction, fertilization

Phase of Fertilization

1. Corona Radiata Penetration

2. Zona Pellucida Penetration

3. Fusion of Sperm and Oocyte

Phase of Fertilization: Corona Radiata Penetration

• 1st phase

• Sperm reaching secondary oocyte

  • Initially prevented entry by corona radiata and zona pellucida

• Can push through cell layers of corona radiata

Phase of Fertilization: Zona Pellucida Penetration

• Acrosome Reaction:

  • Release pf digestive enzymes from acrosomes

  • Allows sperm to penetrate zona pellucida

• After penetration of secondary oocyte:

  • Immediate hardening of zona pellucida, preventing other sperm from entering this layer

  • Ensures only one sperm fertilizes the oocyte

Polyspermy

• If two sperm enter simultaneously

• Immediately fatal with 23 triplets chromosomes

Phase of Fertilization: Fusion of Sperm & Oocyte

• In the plasma membranes of sperm & oocyte

  • Immediate fuse; only sperm nucleus enters oocyte

• Forms an ovum after second meiotic completion

• Nucleus of sperm and ovum pronuclei

• Zygote: single diploid cell form

Pronuclei

• Each with haploid number of chromosomes

• Fuse to become diploid nucleus

Cleavage

• Rapid mitotic divisions increase cell number without increasing overall size

• Before 8-cell stage

  • Become tightly compacted after 3rd cleavage divisions

  • Compaction: process by which contact between cells in increased to the max

Cleavage: Morula

• 16-cell stage; Pre-embryo continues division

• Develops fluid-filled cavity, blastocyst cavity

Cleavage: Blastocyst

• Fluid-filled cavity

• Trophoblast: outer ring of cells surrounding cavity

  • Will form the chorion

• Embryoblast: packed cells within one side of blastocyst

  • Will form embryo proper

  • Cells pluripotent, able to develop into any tissue

Transit of the Pre-embryo through the uterine tube: Fertilization through implantation

Implantation

• Blastocyst embeds in uterine wall (day 7)

  • Burrows into the endometrium (implantation)

• Human Chorionic Gonadotropin (hCG) is secreted, maintaining the corpus luteum for hormone production

• Placenta beings to form by the 2nd week

  • Pregnancy detection

2 layers of Trophoblast

• Cytotrophoblast: Inner layer

• Syncytiotrophoblast: Outer layer

  • Produces hCG

Hormone levels during pregnancy

Clinical View: Infertility

• Inability to conceive and maintain a pregnancy

• Multiple causes:

  • Blocked uterine tubes

  • Caused by pelvic inflammatory disease or endometriosis

  • Ovulation disorders

  • Anti-sperm antibodies or low sperm count

  • Abnormal sperm, impaired sperm delivery

Clinical View: Infertility Treatments

• Intrauterine insemination

• Oral medications (Clomid)

• In virto fertilization (IVF)

• Donor oocytes

Clinical View: Chromosomal Abnormalities and Spontaneous Abortion

• Occurs regularly during gametogenesis, fertilization, or cleavage

• If severe, result in spontaneous abortion (miscarriage)

• Many within 2 to 3 weeks after fertilization, before pregnancy known

• Perhaps 50% of pregnancies terminated from spontaneous abortion

  • Half from chromosomal abnormalities

Changes to embryoblast

• By day 8 (2nd week)

• Cells start forming two layers:

  • Hypoblast layer adjacent to blastocyst cavity

  • Epiblast layer adjacent to amniotic cavity

• Together form flat disc - bilaminar germinal disc

Extraembryonic membranes

• Formed by bilaminar germinal disc and trophoblast

  • Mediate between them and environment

• Protects embryo

• Assist in nutrition, gas exchange, and removal of waste

Extraembryonic membranes: Yolk Sac

• 1st extraembryonic membrane to develop

• Continuous with hypoblast layer

• Does not store yolk (like birds)

• Important site for early blood cell and blood vessel formation

Extraembryonic membranes: Amnion

• Membrane continuous with epiblast layer

• Eventually encloses entire embryo in fluid-filled sac - amniotic cavity

• Protects membrane from drying out

• Specialized to secrete amniotic fluid bathing embryo

Extraembryonic membranes: Chorion

• Outermost extraembryonic membrane

• Formed from cytotrophoblast cells and syncytiotrophoblast

• Cells blend with functional layer of endometrium

• Eventually form placenta

  • Site of nutrient exchange between embryo and mother

Placenta

• High vascular structure

Functions:

• Site exchange of nutrients, wastes, and respiratory gases between maternal and fetal blood

• Transmits maternal antibodies to developing embryo or fetus

• Produces estrogen, progesterone, and hCG

  • Maintains and builds the uterine

Placenta: Connecting Stalk

• Connects early embryo to placenta

• Eventually contains umbilical arteries and veins

• Precursor to future umbilical cord

Placenta: Chorionic Villi

• Fingerlike structures formed from chorion

• Containing branches of umbilical vessels

Placenta: Gas and Nutrient exchange

• Functional layer of endometrium with maternal blood vessels

• Maternal blood does not mix with fetal blood

• Bloodstreams so close that nutrients and gases mix

• O₂ diffusing from maternal blood to fetal blood

• CO₂ diffusing from fetal to maternal blood

Placenta: Selectively permeable

• Example: respiratory gases passing freely

• Microorganisms and certain maternal hormones prevented

Some harmful substances can cross:

• Example: viruses, bacteria, drugs, alcohol, and toxins

• May cause birth defects or death

Formation of Extraembryonic Membranes: Week 3

Formation of Extraembryonic Membranes: Early Week 4

Formation of Extraembryonic Membranes: Late Week 4

Gastrulation¹

• Critical period of development; occurs during third week

• Epiblast forms three primary germ layers

  • Cells from which all body tissues develop

  • Ectoderm, mesoderm, endoderm

• Three-layered structure called an embryo

Gastrulation²

• Begins with formation of primitive streak

  • Thin depression on surface of epiblast

• Primitive node

  • Cephalic end of streak

  • Consists of elevated area surrounding small primitive pit

• Invagination:

  • Cells detaching from epiblast layer

  • Migrate through primitive streak between epiblast and hypoblast layer

Formation of three primary germ layers:

1. Ectoderm: Becomes nervous system, epidermis

2. Mesoderm: Becomes muscles, bones, heart, kidneys

3. Endoderm: Becomes digestive, respiratory, and urinary linings

Embryonic Folding

• Flattened, disc-shaped 3 week embryo

• Starts to fold on itself during late 3rd and 4th week

• Two types of folding:

  • Cephalocaudal and Transverse

Embryonic Folding: Cephalocaudal Folding

• Occurs in cephalic and caudal regions of region

• Rapid growth of embryonic disc and amnion

• No growth of yolk sac

• Causes head and tail to fold on themselves

Embryonic Folding: Transverse Folding

• Left and right sides fold inward, creating a cylindrical body

• Fusing of sides of embryonic disc in midline

• Ectoderm solely along exterior of embryo

• Endoderm confined to internal region of embryo

• Yolk sac pinching off from most endoderm

  • Except vitelline duct

• Creates torso region

Differentiation of ectoderm

• On external surface of cylindrical embryo

• Responsible for formng nervous system tissue: Neurulation

• Forms:

  • Epidermis, sense organs, pituitary gland, adrenal medulla, enamel of teeth, lens of eye

Three Primary Germ Layers and Their Derivatives

Five categories of Mesoderm

• Notochord

• Paraxial mesoderm

• Intermediate mesoderm

• Lateral plate mesoderm

• Head mesenchyme

Five categories of Mesoderm: Notochord

• Formed by tightly packed midline group of mesodermal cells

• Basis for central body axis and axial skeleton

• Induces formation of neural tube

Five categories of Mesoderm: Paraxial Mesoderm

• Found on both sides of neural tube

• Forms somites, block-like masses

  • Forms axial skeleton, muscle, and cartilage, dermis, and connective tissue

Five categories of Mesoderm: Intermediate Mesoderm

• Lateral to paraxial mesoderm

• Forms most of kidneys, ureters, and reproductive system

Five categories of Mesoderm: Lateral Plate Mesoderm

• Most lateral layers of mesoderm

• Forms spleen, adrenal cortex, and cardiovascular system

• Serous membranes and connective tissue of limbs

Five categories of Mesoderm: Head mesenchyme

Forms connective tissues and musculature of face

Differentiation of endoderm

• Becomes innermost tissue after transverse folding

• Forms:

  • Linings of GI, respiratory, urinary, and reproductive tracts

  • Tympanic cavity, auditory tube

  • Liver, gallbladder, pancreas, palatine tonsil, thyroid and parathyroid glands, thymus

Organogensis

• Organ development when layers have formed and folding complete

• By 8 weeks, upper/lower limbs have adult shape and most organ system have rudimentary form

• Teratogens: substances causing birth defects or death (drugs or viruses)

• Peak development period: time where most organization and construction of an organ occurs

Fetal period (Weeks 9-38)

• Growth and organ maturation

• Crown-rump length (CRL) and weight increase significantly

• Movement begins (quickening)

• Last two months: Rapid weight gain and lung maturation

Pregnancy: First Trimester

• First 3 months of pregnancy

• Zygote becoming embryo and then early fetus

Pregnancy: Second Trimester

• 4 to 6 months

• Growth of fetus and expansion of maternal tissues

Pregnancy: Third Trimester

• 7 to 9 months

• Fetus growing most rapidly

• Mother’s body preparing for labor and delivery

Hormonal Changes: Estrogen & Progesterone

• Produced by corpus luteum during 1st trimester. Mostly produced in placenta in 2nd & 3rd trimesters.

• High levels suppressing FSH and LH secretion

  • Ovarian cycle and follicular development arrested

• Facilitate:

  • Uterine & mammary gland enlargement, and fetal growth

  • Faster-growing nails & fuller hair

  • Relaxation of ligamentous joints

  • Uterus functional layer growth due to progesterone

Hormonal Changes: Relaxin

• Secreted by corpus luteum and placenta

• Promotes blood vessel growth ini uterus

Hormonal Changes: Corticotropin-releasing hormone (CRH)

• Secreted from placenta in large amounts

• Role in length of pregnancy and timing of childbirth

• Responsible for aldosterone rise in mother

  • Promotes fluid retention and edema

Hormonal Changes: Human placental lactogen (HPL)

• Secreted from placenta

• Affects how pregnant woman metabolizes certain nutrients

  • Mother metabolizing more fatty acids instead of glucose

  • Inhibits effects of insulin; more glucose available for fetus

Hormonal Changes: Prolactin

• Increased levels (10x) produced by anterior pituitary

• Ensures lactation occurs after giving birth

Hormonal Changes: Oxytocin

• Increased levels produced by hypothalamus

• Involved in uterine contractions

• Involved in milk expulsion from mammary glands

• Increased in second and third trimester

  • In response to rising estrogen levels

Uterine expansion

• Begins once implantation occurs

• By 12 weeks, uterus just superior to pubic symphysis

• Most of enlargement due to:

  • Muscle hypertrophy, hyperplasia, placental growth, and amniotic fluid

• By 16 weeks, fundus at midpoint between pubic symphysis and umbilicus

• By ninth month fundus at xiphoid process of sternum

Melanocyte-stimulating hormoe

• Secreted by placenta

• Darkening of areola and nipples, linea alba, and now linea nigra

• Growth of mammary glandular tissue

  • Development of additional acini

Increased insulin resistance in pregnancy can cause

• Due to increased levels of corticosteroids, estrogen, progesterone, and HPL

• Can lead to gestational diabetes in mother

Morning Sickness

• Occurs in 1st trimester; not just in the morning

• Some with a little nausea, others with severe symptoms (hyperemesis gravidarum [HG])

• Cause unknown, possibly due to high hormones

Nutrition Changes

• Weight gain due to fetus, fluid retention, adipose tissue, etc.

• About 300 extra calories/day needed

• Require adequate folic acid, calcium, protein, and iron

Clinical View: Gestational Diabetes

• Diabetes that first develops during pregnancy

• Increased insulin resistance and high blood glucose

• Appearing in 2nd trimester

• May develop high blood pressure and complications; risk of large baby

  • Increased risk of cesarean section and birth complications, hypoglycemia

• Special diet to regulate blood glucose levels

• At increased risk for type 2 diabetes later in life

Body System Changes:

• Cardiovascular: Blood volume increases by 50%

• Respiratory: Tidal volume increases

• Urinary: Increased filtration due to fetal waste

• Digestive: Increased nutrient absorption, but also reflux, nausea

Clinical View: Preeclampsia

• High blood pressure occurring by second half of pregnancy

• Risk factors: obesity, diabetes, older age, and previous preeclampsia

• Cause is unknown but general risks of hypertension for mother

• Only cure is giving birth, with medications or labor induction

Eclampsia:

• High blood pressure causing seizures

• Medical emergency

Stage of Labor: Dilation Stage

• 1st stage of labor

• Longest stage; cervix dilates to 10 cm

• Amniotic sac may rupture (water breaking)

• Ends when cervix if effaced (thinned)

Dilation variability

• Nulliparous women (who have not given birth) experience longer dilation stage, 8 to 24 hours

• Parous women (who have given birth) may be in this stage for 4 to 12 hours

Stage of Labor: Expulsion Stage

• Usually 30 mins to several house

• Baby is pushed out of the birth canal

• Crowning: When first part of baby’s calvarium distends vagina

• Episiotomy: sometimes necessary

  • Perineal muscle surgically incised

Stage of Labor: Placental Stage

• Placenta is expelled (afterbirth)

• Uterus continuing to contract

  • Compresses uterine blood vessels; displaces placenta from uterine wall

• Afterbirth:

  • Placenta and remaining fetal membranes; 30 minutes

  • Complications may occur if fragments are left

Clinical View: Fetal Positioning and the Dilation Stage

• Fetus in vertex position - head down toward sacrum

  • Ideal position for pushing

• Breech position

  • Buttocks first and may delay cervical dilation

• Variant positions extraction

  • Forceps, vacuum may be needed

  • Cesarean section

Clinical View: Vaginal Bacteria and the Infant Microbiome

Vaginal delivery vs cesarean (C-section) delivery

• Exposure to fecal bacteria during vaginal delivery

  • Infants have gut microbiome similar to the mother

  • Diverse, protective, supported by nutrients in breast milk

• Exposure to surrounding environment during C-section

  • Hospital-acquired bacteria

  • Less diverse, prone to health issues later in life

True vs False Labor:

• True Labor: Regular contractions, cervical dilation

• False Labor (Braxton-Hicks): Irregular, non-progressive contractions

Postnatal Changes for the Newborn

• Respiratory changes. in neonate

  • Fetus after being expelled from uterus

  • Fetal lungs not full inflated prior to birth

Neonatal Adjustment

• Respiratory System: First breath expands lung

• Circulatory System: Fetal shunts close

• Thermoregulation: Brown fat helps generate heat

• Digestive System: Meconium (first stool) is passed

Clinical View: Preterm (Premature) Birth

• Baby born before start of 37th week pregnancy

• Preterm births earlier than 24 weeks rarely survive, may have severe medical issues

• Usually very low birth weight

• May have jaundice, breathing issues, problems regulating body temp, and feeding difficulties

Postpartum

• Time period after giving birth

• Woman’s body undergoing further changes

  • Feed neonate

  • Return to pre-pregnancy form and function

Postpartum Hormonal Changes: Estrogen & Progesterone

• Mood swings, postpartum depression risk - Baby Blues

• Hair reverts back to normal hair loos cycle

  • Peak in loss about 3 to 4 months after delivery

• Chemoreceptors less sensitive to CO₂ due to low progesterone

• Corticotropin-releasing hormone (CRH). Placenta stops producing.

Lochia

• Portion of blood volume, mucus endometrial tissue

• Expelled via the vagina

• Heaviest first five days, continues for several weeks

Lactation: Prolactin

• Produced by anterior pituitary

• Responsible for milk production

• Secretion inhibited by dopamine in nonpregnant women and in men

• Increased by high levels of estrogen

Lactation: Colostrum (initial milk)

• Produce by mammary glands

  • During late pregnancy and first few days after birth

• Watery, yellowish, milk like substance and lower concentration of fat than true breast milk

• Rich in immunoglobulins, especially IgA

• Laxative effect

Lactation: Breast milk

• Starts to be produced few days postpartum

• Higher fat content than colostrum

• Has essential fatty acids, enzymes for digestion, and immunoglobulins

• More easily digestible than breast milk substitutes

Milk Letdown

• Oxytocin stimulates release via positive feedback

• With suckling, mechanoreceptors in breast stimulated

• Send signals to hypothalamus

• Hypothalamus is stimulated to produce oxytocin, released into blood by posterior pituitary

• Targets myoepithelial cells in mammary acini

  • Cells contract, releasing breast milk from acini

• As milk released, infant continuing to nurse

  • Facilitates further milk release

Genetics¹

• Heredity: Transmission of genetic characteristics from parent to child

• Genetics: Field of biology studying heredity and transmission patterns

• Karyotype: Display of chromosomes pairs, ordered and arranged by size and similar features

• Homologous Chromosomes: Paired chromosomes with genes for equivalent biological characteristics

Genetics²

• Sex Chromosomes: Last two chromosomes containing genes that specify sex

• Genes: Units of DNA that code for a protein

• Locus: Specific space where each gene is located on a chromosome

• Alleles: Variants of one gene found at some locus on homologous chromsomes

  • Example: alleles determining type A or type O blood

Genetics³

• Dominant allele

  • Expresses, or physically shows, the trait

  • Represented by capital letter

• Recessive allele

  • Trait is masked, represented by lowercase letter

  • Expressed only if present on both homologous chromosomes

• Punnet Square:

  • Square showing specific gene combinations resulting from two parents

  • Gives probability that a particular gene combination can occur

Genetics⁴

• Homozygous: If identical alleles present

• Heterozygous:

  • Both dominant and recessive allele present

  • But only dominant allele expressed

  • Expression of the receive allele may appear to skip generations

    • Its phenotype is masked by the dominant allele

Karyotype

Chromosomes & Heredity

• Humans have 46 chromosomes (23 pairs)

• Autosomes (22 pairs) vs. Sex Chromosomes (XX/XY)

• Genotype: Genetic makeup

• Phenotype: Physical trait

Patterns of Inhertitance:

• Dominant-Recessive: Dominant allele expressed (e.g. eye color)

• Incomplete Dominance: Blended traits (e.g. sickle cell trait)

• Codominance: Both alleles expressed (e.g. ABO blood type)

• Polygenic Inheritance: Multiple genes influence traits (e.g. height, skin color)

• X-linked Inheritance: Traits carried on the X chromosome (e.g. color blindness, hemophilia)

Sex-linked traits

• Traits expressed by genes on X or Y chromosomes

• 900 to 1400 genes on X chromosome

• Most not involved in sex determination

• 70 to 200 genes on Y chromosome

• Mostly for male development

• Sex-linked traits most often involve X chromosome

X-linked recessive traits