35 Fertilization, Embryology, Parturition and Lactation

Quiz 6

• Quiz 6 will be on Thursday, May 29 and will cover lectures 32-35.

Lecture 35: Fertilization, Embryology, Parturition, and Lactation

• Topics covered:
  • Fertilization and implantation.
  • Early embryonic development.
  • Structures produced by primary germ layers.
• Embryonic membranes.
  • Role of placenta and umbilicus.
  • Changes associated with fetal growth.
  • Difference between a fetus and an embryo.
  • Hormones secreted during pregnancy.
  • Three stages of labor.
  • Physiology of lactation.

Overview of Human Development

• Fertilization initiates with the union of gametes.
• Developmental biology studies changes from fertilized egg to old age.
• Embryology studies the 38 weeks of development in utero.

Prenatal and Postnatal Periods

• Prenatal period: time in the womb.
• Postnatal period: period following birth.

Prenatal Development

• Prenatal development spans from conception to birth.
• Growing offspring (conceptus) develops during the gestation period which lasts 38 weeks and is divided into three stages:
  1. Pre-embryonic
  2. Embryonic
  3. Fetal

Developmental Stages

• Pre-embryonic Period (Weeks 1 and 2):
  • Zygote divides mitotically to produce a multicellular blastocyst.
  • Blastocyst implants in the uterus.
• Embryonic Period (Weeks 3 through 8):
  • Blastocyst grows, folds, and forms rudimentary organ systems.
  • It is now called an embryo.
• Fetal Period (Weeks 9 through 38):
  • Embryo is now called a fetus.
  • The fetus grows larger and develops until its organ systems can function without assistance from the mother.

Postnatal Period

• Involves rapid developmental changes in the first few months after birth.
• Divided into five stages:
  1. Neonatal period: birth to 1 month
  2. Infancy: 1 month to 2 years
  3. Childhood: 2 years to puberty
  4. Adolescence: puberty to sexual maturity
  5. Adulthood: sexual maturity to death

Senescence

• Development ends, leading to degeneration of tissues and organs, ultimately resulting in death.

Pre-Embryonic Period (Weeks 1 and 2)

• Begins with fertilization of a secondary oocyte.
• The blastocyst moves to the uterus and implants in the endometrium.
• Extraembryonic membranes form.

Fertilization

• Fusion of sperm and secondary oocyte forming a zygote.

Events Before Fertilization

• A. Capacitation
• B. Acrosomal reaction
• C. Cortical reaction

A. Capacitation

• Sperm becomes fully motile and capable of fusing with the oocyte.
• Alkaline semen allows sperm to swim faster.
• Fluids in the female reproductive tract alter the sperm plasma membrane.
• Progesterone from the oocyte chemically attracts sperm by chemotaxis.

B. Acrosomal Reaction

• Releases hyaluronidase and acrosin from the acrosome in the head of the sperm.
• Hyaluronidase breaks down granulosa cells of the corona radiata surrounding the secondary oocyte.
• Acrosin is a protease.
• Sperm bind receptors in the zona pellucida to open Ca^{+2} channels.
• Ca^{+2} influx releases additional hyaluronidase and acrosin, digesting holes in the zona pellucida.
• Many sperm are required to release enough enzymes for a single sperm to fertilize the oocyte.

C. Cortical Reaction

• Penetration of sperm produces changes in the oocyte and zona pellucida, preventing additional sperm from entering.
• Sperm entry releases cortical granules containing digestive enzymes.
• Destroys sperm-binding receptors.
• Additional sperm are rejected, preventing polyspermy (3n).

Fertilization Process

1. Sperm undergo capacitation as they migrate to the oocyte.
2. Acrosomal reaction releases enzymes from the head of the sperm.
3. The sperm binds to the plasma membrane of the oocyte.
4. Sperm entry stimulates the cortical reaction, which destroys sperm-binding receptors.
5. Additional sperm cells are rejected.
6. The sperm nucleus swells to form a male pronucleus.
7. The oocyte completes meiosis II, and the ovum's nucleus swells to form a female pronucleus.
8. A spindle forms between the male and female pronuclei, and the chromosomes intermix.

Post-Fertilization Events

• Sperm nucleus forms the male pronucleus, which is released into the cytoplasm of the oocyte.
• The oocyte completes meiosis II and forms the female pronucleus.
• Formation of spindle between pronuclei and chromosomes.

Cleavage and Blastocyst Formation

• Pronuclei combine through amphimixis, forming a diploid zygote.

Process of Cleavage and Blastocyst Formation

• The zygote begins cleavage 30 hours after fertilization.
• Cleavage produces identical cells called blastomeres.
• By day two, there are 4 cells, and by the third day, 16 cells.
• By day 3 cells differentiate in 16 cell stage to become future tissues.
• The conceptus is now a morula (“little raspberry”) and covered by the zona pellucida.
• As mitotic divisions occur, the conceptus moves through the uterine tube and into the uterine cavity.
• By day 4 glycogen-rich secretions (uterine milk) from endometrial glands nourish conceptus.
• The blastocyst hatches from the zona pellucida.
• Blastomeres form an internal fluid-filled cavity.
• Days 4-7 The blastocyst prepares for implantation.
• The outer layer (trophoblast cells) surrounds the fluid-filled cavity to help form the placenta.
• The inner cluster (inner cell mass) becomes the embryo.

Twins

• During the first 8 days, cells may separate into 2 individuals, forming monozygotic or identical twins.
• Dizygotic or fraternal twins occur when 2 secondary oocytes ovulate.

Implantation (Days 4-7)

• The blastocyst attaches to the endometrium of the uterus.
• The trophoblast invades the stratum functionalis by secreting digestive enzymes, degrading the endometrial lining.
• The trophoblast divides into the inner cytotrophoblast and the outer syncytiotrophoblast.
• Synctiotrophoblast secretes enzymes digesting uterine cells.
• The inner cell mass differentiates into the hypoblast and epiblast, forming the embryonic disc.
• The amniotic cavity forms in the epiblast.

Process of Implantation

• Days 4-7: The blastocyst attaches to the stratum functionalis, and the trophoblast differentiates into the syncytiotrophoblast and the cytotrophoblast.
• Day 8: The syncytiotrophoblast digests the uterine wall as the inner cell mass differentiates into the hypoblast and epiblast.
• Day 12: The syncytiotrophoblast reaches maternal blood vessels and degrades them, creating lacunae; the amniotic cavity forms within the epiblast.
• Day 16: The blastocyst is fully implanted when completely covered by uterine tissue. The three primary germ layers are present.
• By day 12, the syncytiotrophoblast invades the uterine lining and reaches maternal blood vessels, digesting vessel walls.
• Blood pools into lacunae or intervillous spaces.
• The syncytiotrophoblast contacts nutrients in uterine glands.
• The syncytiotrophoblast secretes human chorionic gonadotropin (hCG), stimulating the corpus luteum to secrete estrogen and progesterone.
• hCG is detected in pregnancy tests.
• By day 16, blastocyst moves deeper and becomes covered by maternal epithelial cells and is considered fully implanted.

Ectopic Pregnancies

• Occur when the blastocyst implants in a different site than the uterus (occurs in 1-2% of pregnancies).

Extraembryonic Membranes

• Protect the embryo and assist with vital functions.
• Appear in week 2 of development and continue during the embryonic and fetal periods.
• Include:
  • Yolk sac
  • Amnion
  • Chorion
  • Allantois

Functions of Extraembryonic Membranes

• Yolk Sac
  • Forms from hypoblast cells.
  • Forms part of digestive tract, first blood cells and blood vessels, and first germ cells.
• Amnion
  • Develops from epiblast, enclosing the embryo in a fluid-filled amniotic cavity.
  • The amniotic fluid protects the embryo from trauma, maintains temperature, and allows freedom of movement.
  • Penetrated only by the umbilical cord.
• Allantois
  • Outpocketing of yolk sac.
  • Forms the base for the umbilical cord and part of the urinary bladder.
• Chorion
  • Develops from cytotrophoblast and syncytiotrophoblast.
  • Encloses all other membranes and the embryo.
  • Forms chorionic villi that blend with the stratum functionalis, forming the placenta.

Summary of Extraembryonic Membranes

Embryonic Period: Weeks 3-8

• Occurs after implantation, differentiation of the embryonic disc, and development of extraembryonic membranes.
• Starts with gastrulation.
• Gastrulation is the rearrangement and migration of the bilaminar embryonic disc to form the trilaminar embryonic disc.
• The three germ layers are:
  • Endoderm
  • Mesoderm
  • Ectoderm
• The three layers become all organ systems by week 8.
• The placenta forms and begins to provide nutrition and oxygen to the embryo and removes waste.

Gastrulation and Formation of Germ Layers

• Week 3, the primitive streak forms a groove on the surface of the epiblast.
• The primitive streak forms head and tail regions, as well as right and left sides and dorsal and ventral surfaces of the embryo.
• Once the primitive streak develops, gastrulation begins.
• Epiblast cells migrate into and then under the primitive streak by ingression; these cells replace the hypoblast to become the endoderm.
• Epiblast cells migrating between the endoderm and epiblast become the mesoderm, and the remaining cells become the ectoderm.
• Late in week 4, trilaminar disc folds to become more cylindrical. Cephalic and caudal regions fold in on themselves. Left and right sides fold in on the midline.

Organogenesis

• The three primary germ layers (ectoderm, mesoderm, and endoderm) differentiate into organs and organ systems.

Differentiation of Germ Layers

• Ectoderm
  • Forms the epidermis, nervous system, and sense organs.
  • Neurulation is the formation of the brain and spinal cord.
  • The neural tube develops, and primary brain vesicles (forebrain, midbrain, and hindbrain) form.
  • Neural crest cells produce ganglia, nerves, pigmented skin cells, and the adrenal medulla.
• Mesoderm
  • Forms the notochord, somites, ribs, dermis, and skeletal muscles.
  • The notochord supports the body and remains as intervertebral discs.
  • Somites have 3 regions:
    1. Sclerotome (vertebrae and ribs)
    2. Dermatome (dermis)
    3. Myotome (most of skeletal muscles)
  • Also forms gonads, kidneys, spleen, adrenal cortex, cardiovascular system, serous membranes, and connective tissue of limbs.
• Endoderm
  • Forms the epithelium of the digestive, respiratory, urinary, and reproductive systems.
  • Forms the middle ear cavity and auditory tube.
  • Forms thyroid, parathyroid, thymus, palatine tonsils, liver, gall bladder, and pancreas.

Summary of Body Structures Produced by Germ Layers

Summary of Organogenesis

• Rudimentary organs are present by the 4th week of development.
• Exposure to teratogens during organogenesis increases the risk of birth defects because developing tissues and organs are most susceptible to these agents due to rapid growth and development.

Zika Virus

• The Zika virus is dangerous to development as it is spread primarily through infected Aedes mosquitoes.
• Infection during pregnancy can cause serious birth defects, such as microcephaly, likely because it targets neuronal stem cells.

Fetal Period: Week 9 until Birth (Week 38)

Placenta

• In the pre-embryonic period, the embryo receives nutrients through uterine milk and digested endometrial cells until the formation of the placenta in week 12.
• Placentation begins at implantation.
• It is a temporary organ for the exchange of O_2, nutrients, and waste between the mother and fetus through the umbilical cord.
• The umbilical cord connects the placenta to the fetus and contains two umbilical arteries and one umbilical vein.
• Chorionic villi penetrate uterine blood vessels to form blood-filled lacunae. The lacunae merge as a single cavity called the placental sinus.
• At placentation, the stratum functionalis becomes the decidua basalis.
• The placenta develops from fetal and maternal structures. Maternal and fetal blood do not mix due to the placental barrier.
• The placental barrier is formed by maternal and fetal basal lamina, fetal connective tissue, cytotrophoblast, and synctiotrophoblast.
• Placenta allows gases, nutrients, and wastes to pass by diffusion.
• Fetal hemoglobin (hemoglobin F or γ hemoglobin) has a higher affinity to O_2 than adult hemoglobin, allowing for efficient oxygen saturation.
• Secretes: hCG, estrogen and progesterone, human placental lactogen and placental prolactin, and relaxin.

Fetal Development

• Major Events: Ossification begins, eyes well developed, the sex can be determined from genitals (Month 3).
• Month 4: Startle reflexes develop, kidneys well formed, heartbeat heard with stethoscope (CRL 14 cm).
• Month 5: Growth slows, hair on head, skin covered by lanugo, brown fat forms (CRL 19 cm).
• Month 6: Significant weight gain (CRL 23 cm), eyebrows and eyelashes form, eyelids open, lungs produce surfactant.
• Month 7: Fetus turns upside down, subcutaneous fat deposited, testes descend in males (CRL 28 cm).
• Months 8 and 9: Neuronal networks form, organs are growing, lanugo is shed, and blood cells form in the bone marrow (CRL is about 36 cm).

Big Picture of Prenatal Development

1. Fertilization: Sperm cell and secondary oocyte unite in the uterine tube.
2. Pre-embryonic period: Chromosomes from the male and female pronuclei combine and form the zygote. Cleavage produces a blastocyst that implants in the uterine endometrium.
3. Embryonic period: Cells in the blastocyst migrate to form the three germ layers. Differentiation of the three germ layers results in organogenesis.
4. Fetal period: The placenta completes its development and provides nutrients to the fetus. Tissues and organs continue to mature until gestation is complete at 38 weeks.

Pregnancy and Childbirth

• Maternal changes during pregnancy divided into three trimesters, each lasting about 3 months.

Trimesters

• First trimester (Months 1-3): Most critical stage and more spontaneous abortions occur. May be characterized by morning sickness and fatigue.
• Second trimester (Months 4-6): Uterus and abdomen expand. Some relief from morning sickness. Fetal movements may be felt.
• Third Trimester (Months 7-9): Uterus and abdomen enlarge further. Backaches and pressure on internal organs.

Hormonal Changes

• hCG, relaxin, human placental lactogen, Corticotropin-releasing hormone (CRH), and oxytocin are all involved in pregnancy.
• The syncytiotrophoblast secretes hCG; it maintains corpus luteum to secrete estrogen and progesterone.
• The anterior pituitary inhibits follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stopping the normal ovarian cycle.
• hCG declines after the 4th month, when the corpus luteum is no longer needed because the placenta secretes estrogen and progesterone.

Hormones

• Relaxin: From the placenta, it suppresses uterine contractions and loosens the pubic symphysis and sacroiliac joints.
• Human Placental Lactogen (hPL): Stimulates breast development. Prepares mammary glands to secrete milk.
• Corticotropin-releasing hormone (CRH): A week 12 cortisol from the adrenal cortex matures fetal lungs and produces surfactant.
• Prolactin: From the anterior pituitary, it stimulates milk production from mammary glands.
• Oxytocin: From the fetal and maternal hypothalamus during labor, it stimulates uterine contractions and milk release from mammary glands.

Anatomical and Physiological Changes

• Before pregnancy, the uterus is the size of a fist.
• By month 4, the uterus fills the pelvic cavity and pushes into the abdominal cavity. This enlargement results from the hypertrophy of the myometrium, placental growth, and increased amniotic fluid.
• By month 7, the uterus reaches the umbilicus. Abdominal organs are displaced upward, compressing the diaphragm and pressing on the urinary bladder.
• Changes in the center of gravity may cause lordosis and backaches to occur.
• Breasts enlarge due to increased glandular and adipose tissue.

Childbirth (Parturition)

• Fetus is normally expelled from the uterus through the vagina.
• This series of events is called labor.
• The fetal adrenal cortex produces cortisol, which stimulates the placenta to secrete a high level of estrogen.
• The high estrogen level stimulates the uterus to form oxytocin receptors.
• Both the fetal hypothalamus and the maternal hypothalamus secrete oxytocin, which stimulates the placenta to secrete prostaglandins.
• Prostaglandins dilate the cervix and, along with oxytocin, increase the strength of uterine contractions.
• A positive feedback mechanism begins when cervical stretching triggers the release of more oxytocin and prostaglandins.

Stages of Labor

• The three stages of labor are dilation, expulsion, and placental.

1. Dilation Stage

• From the onset of labor until the cervix is fully dilated (10 cm).
• This is the longest stage of labor (8-24 hours).
• The amnion ruptures, releasing amniotic fluid.
• The head of the fetus enters the pelvis.

2. Expulsion Stage

• From full dilation to delivery.
• Assisted by contractions and voluntary “pushing” by the mother.
• Lasts 30 minutes to 1 hour.
• Can be complicated by breech birth or non-vertex presentation.

3. Placental Stage

• After delivery, the placenta and extraembryonic membranes (afterbirth) are delivered.
• The uterus contracts, compressing arteries to limit bleeding.
• Lasts about 30 minutes.

Lactation

• Lactation is the production and release of breast milk from the mammary glands.
• Increase in placental estrogen, progesterone, and human placental lactogen (which stimulates prolactin from the anterior pituitary).
• After birth, colostrum is secreted (rich in protein and IgA but low in fat).
• True breast milk is produced a few days later.
• Acts as a laxative to cleanse meconium (fecal material first excreted by newborn).
• Prolactin is no longer inhibited by estrogen and progesterone from the placenta.

1. Infant suckling triggers the maternal hypothalamus to produce oxytocin, and the maternal anterior pituitary to produce and release prolactin.
2. Oxytocin stimulates myoepithelial cells of the breast to contract (let-down reflex).
3. Prolactin stimulates the mammary glands to produce additional milk.
4. A positive feedback mechanism is responsible for the continued production of milk, which occurs as long as the infant continues to suckle.