Fertilization and Implantation (Creamer) Flashcards

1
Q

Describe the general steps of fertilization:

A

(occurs ~day 15-16 of menstrual cycle, allows for recombination of genetic material)

1) sperm cell moves through follicular cells and binds to zona pellucida
2) rise in Ca2+ within sperm triggers exocytosis of acrosome (acrosomal reaction) which contains hydrolytic enzymes
3) hydrolytic enzymes are released, locally dissolving the zona pellucida; whip like action of the sperm tail pushes the head toward oocyte membrane
4) sperm head now lays sideways w/ microvilli of the oocyte surrounding, fusing the two membranes; contents of sperm cell enter the oocyte, while the membrane remains behind
5) rise in Ca2+ within the oocyte triggers the cortical reaction, exocytosis of granules that lay immediately beneath the plasma membrane; these enzymes lead to changes in zona pellucida proteins, causing the zona pellucida to harden, preventing entry of other sperm cells
6) rise in Ca2+ also induces completion of oocyte’s second meiotic division and the formation of second polary body, usually located next to the first polar body, creating the female pronucleus
7) head of sperm enlarges and becomes male pronucleus
8) the pronuclei fuse

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2
Q

Where do gametes need to travel to for proper fertilization and how is this achieved?

A
  • both sperm and oocyte must travel to ampulla of oviduct for fertilization to occur (ampulla is middle portion of oviduct)
  • LH surge leads to follicular rupture
  • ovum and surrounding corona radiata get ejected into peritoneum
  • oocyte is swept into oviduct by fimbriae
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3
Q

How do sperm travel to the oviduct?

A
  • ~300 million sperm enter vagina near uterus (<20 million/ejaculate > infertile)
  • ~200 million reach ampulla of oviduct
  • barriers: distance, immune system, secretions, timing
  • myometrium contracts as a result of increased estrogen near ovulation period (helps move sperm through cervic/uterus)
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4
Q

Describe the spermatic states based on biochemistry of the head:

A
  • epididymal: plasma membrane of spermatozoa contains complement of surface molecules (proteins and carbs)
  • ejaculated: surface molecules in epididymal sperm becomes coated w/ seminal plasma proteins that mask portions of the membrane molecules
  • capacitated: occurs when sperm are exposed to female tract environment; the seminal plasma coatings and some surface molecules are removed, exposing portions of the molecules that can bind to zona pellucida of oocyte
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5
Q

What is the purpose of sperm capacitation?

A
  • penultimate step in maturation of spermatozoa and is required to render the sperm competent to fertilize an oocyte
  • two effects: destabalization of the acrosomal head which allows it to penetrate the outer layer of the egg, and chemical changes in the tail that allow for greater mobility of sperm
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6
Q

Describe the process of capacitation in sperm:

A
  • occurs after ejaculation, when the spermatozoa leave the vagina and enter the superior female reproductive tract
  • the uterus aids in capacitation by secreting sterol-binding albumin, lipoproteins, proteolytic, and glycosidasic enzymes
  • incapacitated sperm bind actively to epithelial cells of oviductal isthmus and become unbound when they are capacitated
  • binding: slows capacitation process, extends sperm lifespan (several days), and increases probability sperm will be in oviduct when egg is ovulated
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7
Q

Describe the process of activation within sperm:

A
  • occurs during capacitation and is also triggered by chemical signals from oocyte
  • involves change in flagella motion: from wave-like to whip-like, necessary for sperm to detach from epithelium of oviduct, increases mobility, helps propel sperm through outer layers of egg to reach the plasma membrane
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8
Q

What are the 3 barriers sperm has to breach to reach the oocyte?

A
  • the expanded cumulus (corona radiata), multiple sperm bind here but only 1 fertilizes the egg
  • zona pellucida
  • plasma membrane of the oocyte
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9
Q

What is the expanded culumus (corona radiata) componsed of and how do sperm penetrate this layer?

A
  • predominantly hyaluronic acid
  • sperm digest this via membrane bound hyaluronidase
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10
Q

What is the zona pellucida composed of and how do sperm penetrate this layer?

A
  • glycoproteins: ZP1, ZP2, ZP3, ZP4
  • sperm contains ZP3 receptors (available after capacitation)
  • binding of ZP3 receptor to ZP3 triggers acrosome reaction
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11
Q

What occurs during the acrosomal reaction?

A
  • binding of ZP3 receptors of sperm to ZP3 of oocyte zona pellucida triggers acrosomal reaction
  • inner sperm plasma membrane fuses w/ outer acrosomal membrane to release contents of acrosomal vesicle
  • these enzymes digest zona pellucida
  • sperm can enter the holes created in zona pellucida
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12
Q

How does the sperm enter the plasma membrane of the oocyte and what occurs immediately after this?

A
  • sperm possess protein, Izumo, which binds to Izumo receptor on oocyte
  • entire sperm enters the egg during fusion, and sperm DNA instantly de-condenses
  • membrane called pronucleus forms around the DNA
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13
Q

What is the cortical reaction and what is the purpose of this event?

A
  • cortical reaction triggered by fusion of sperm and egg
  • oocyte releases high level of Ca2+ which causes alteration of ZP proteins to block binding of additional sperm
  • hyaluronic acid, proteoglycans, and proteinases are released and hydrated
  • zona pellucida forms a physical barrier
  • this reaction prevents polyspermy
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14
Q

What event stimulates the oocytes completion of meiosis II and what occurs following this stimulation?

A
  • the rise of Ca2+ within the oocyte stimulates completion of meiosis II: MAPK proteins break down and 2nd polar body is released
  • egg activation occurs as sperm DNA condenses
  • pronucleus forms around female chromosomes
  • male and female chromosomes replicate as pronuclei move together
  • fusion of pronuclei initiates first embryonic cleavage (signifies beginning of embryonic development)
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15
Q

What happens during 1 week of development?

A
  • cleavage: cell division w/o growth
  • embryo remains ~100 μm in diameter
  • by day 3, reaches ~16 cell stage morula
  • around day 4, early blastocyst develops
  • around days 6-8, implantation occurs
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16
Q

Describe the process of cleavage in terms of embryonic development:

A
  • individual cells = blastomeres
  • mitotic divisions maintain 2n (diploid) complement
  • cells become smaller
  • balstomeres are totipotent (able to become any cell type)
  • embryo reaches 16-cell morula by day 3
17
Q

Describe the compaction and blastocyst development:

A
  • outer cells of morula increase cell-cell adhesion via desmosomes and tight junctions: form trophoectoderm, increase Na+ transport and osmosis to form blastocele
  • inner cells become inner cell mass (ICM): will form embryo proper, pluripotent
  • early blastocyst formed around day 3, late blastocyst around day 5
18
Q

Describe the process of blastocyst hatching:

A
  • hatching of embryo from zona pellucida prior to implantation
  • trophoblasts secrete proteases that digest ZP
  • inability to hatch can result in infertility
  • premature hatching can result in abnormal implantation
19
Q

What does the blastocyst secrete and why?

A
  • blastocyst secretes molecules that promote maintenance of pregnancy, implantation and placental development
  • secretes immunosuppressive and immunoregulatory factors (e.g. platelet-activating factor, human chorionic gonadotropin, early pregnancy factor, immunosuppressive factor, prostaglandin E2, interleukin 1-α, interferon-α, leukemia inhibitory factor, and colony-stimulating factor)
20
Q
  • hormone secreted by trophoblasts and syncytiotrophoblasts
  • measurable in blood ~8 days post ovulation
  • structure closely related to LH
  • prevents involution of corpus luteum: prevents menstruation, leads to increased secretion of progesterone and estrogen
  • autocrine growth factor: stimulates trophoblast growth/development and placental growth
A

human chorionic gonadotropin (hCG)

21
Q

Describe the apposition stage of implantation:

A
  • contacts occurs between endometrium and trophoblasts, typically within a crypt in endometrium
  • inner cell mass rotation near endometrial epithelium
22
Q

Describe the attachment stage of implantation:

A
  • trophoblast cells adhere to luminal endometrial epithelium
  • interaction between surface proteins on trophoblasts and epithelial cells occurs
  • initiates changes in endometrial stroma (decidualization): increase vascular permeability, intracellular matrix composition, stromal cell morphology
23
Q

Describe the invasion stage of implantation:

A
  • degradation of endometrial epithelium cells
  • trophoblast fusion and formation of syncytiotrophoblasts (multinuclear, multicellular syncytium)
  • synctiotrophoblast (SB) protrudes through basement membrane and reaches endometrial stroma
  • SB’s secrete autocrine and paracrine factors (metalloproteinases, angiogenic factors) to increase invasion/degrade matrix
  • primary metabolic substrates of degraded cells/matrix are taken up by conceptus
  • fingerlike projections reach maternal blood supply
  • surface epithelium becomes restored as conceptus invades
24
Q
  • cells that are adhesive, invasive, and posses endocrine functions
  • express adhesive surface proteins (cadherins, integrins): initially bind uterine surface epithelia, as embryo implants bind to components of uterine extracellular matrix
  • break down extracellular matrix: secretion of matrix metalloproteases and other hydrolytic enzymes
  • hCG secretion: maintains viability of corpus luteum (progesterone secretion)
  • highly steroidogenic at 10 weeks: make progesterone at sufficient levels to maintain pregnancy independently of corpus luteum
  • as implantation and placentation process, functions in phagocytosis and bidirectional placental transfer of gases, nutrients, and wastes
A

syncytiotrophoblasts

25
Q

Describe the process of decidualization:

A
  • response of maternal stroma cells to invasion and progesterone
  • endometrial stroma is transformed into enlarged and glycogen-filled decidual cells
  • endometrium is now called decidua and is ready for implantation of embryo
  • decidua forms epithelial-like sheet w/ adhesive junctions that inhibit migration of implanting embryo
  • production of signals prevents embryo from invading myometrium (postpartum hemorrhage)
26
Q
  • implantation that occurs somewhere other than uterine fundus
  • most common site is oviduct (tubal pregnancy)
  • no decidualization occurs
  • invasion is not controlled and can rupture tissues and cause hemorrhage
A

ectopic implantation

27
Q

Describe the process of placentation:

A
  • spaces appear within syncytiotrophoblasts ~day 9
  • lacunae: break maternal capillaries; fill w/ endometrial secretions, maternal blood, and digested matrix for nutrient transfer
  • primary, secondary and tertiary villi form
28
Q

How are primary, secondary, and tertiary villi formed?

A
  • primary villi: proliferation of syncytiotrophoblasts and cytotrophoblasts to lacunae
  • secondary villi: mesenchyme cells from extraembryonic mesoderm invade villi (now called chorionic membrane)
  • tertiary villi: eventually mesenchymal cells form fetal blood vessels de novo