38. Fertilization and Implantation Flashcards

1
Q

Fertilization Process Overview:

  1. The sperm cell weaves past the follicular cells and binds to the ________
  2. A rise in _____ inside the sperm cell triggers the exocytosis of the acrosome, which contains hydrolytic enzymes
  3. Hydrolytic enzymes contained in the acrosomal cap are released. These enzymes locally dissolve the zona pellucida. The whip action of the tail pushes the sperm head toward the oocyte membrane
  4. With the head of the sperm now lying sideways, _______ on the oocyte surround the sperm head. The 2 membranes fuse, the contents of the sperm cell enter the oocyte; the sperm cell membrane remains behind
  5. A rise in _____ inside the oocyte triggers the _______ reaction, in which there is exocytosis of granules that previously lay immediately beneath the PM. The enzymes released lead to changes in the ZP proteins, causing it to harden and preventing additional sperm entry
  6. The rise in _____ inside the oocyte also induces completion of the oocyte’s second meiotic division, and the formation of the second _______, which usually lies next to the first
  7. The head of the sperm enlarges to become the male _____, which then fuses with that of the female
A
  1. Zona pellucida
  2. [Ca]
  3. Microvilli
  4. [Ca]; cortical
  5. [Ca]; polar body
  6. Pronucleus
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2
Q

In terms of the menstrual cycle, when does fertilization typically occur?

A

Day 15-16

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3
Q

Both sperm and oocyte must travel to the _____ for fertilization to occur. The LH surge leads to follicular ____, so that the ovum and surrounding _______ are ejected into the peritoneum

A

Ampulla; rupture; corona radiata

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4
Q

About 300 mill sperm enter the vagina near the uterus, and about 200 will reach the ampulla of the oviduct. What are some barriers they must overcome?

A

Distance, immunological, secretory, timing

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5
Q

Less than 20 million sperm per ejaculate is considered _____ for a male

A

Infertile

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6
Q

What changes occur in the uterus as a result of increased estrogen near the ovulation period?

A

Cervical mucous forms channels to allow motile sperm to pass through; myometrium contractions help to move sperm through cervix/uterus

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7
Q

Sperm must under go _______ in order to fertilize an oocyte; this occurs within the oviduct

A

Capacitation

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8
Q

What changes occur in sperm with capacitation?

A

Altered membrane fluidity d/t removal of cholesterol

Removal of various proteins, carbs, and glycoproteins from the membrane that may block binding sites

Change in membrane potential that may permit calcium influx and acrosome reaction

Phosphorylation of various proteins

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9
Q

Incapacitated sperm bind actively to the epithelial cells of the oviductal ______; they become unbound when capacitation occurs

WHAT is the purpose of them binding here?

A

Isthmus

Purpose is to slow the capacitation process, extending sperm lifespan and preventing too many sperm from reaching the egg. This increases the probability the sperm will be in the oviuct when the egg is ovulated

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10
Q

________ of sperm is associated with sperm capacitation and chemical signals from the oocyte; it involves a change in flagellar motion from wave-like to whip-like

A

Hyperactivation

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11
Q

Why is hyperactivation of sperm necessary with the capacitation reaction?

A

Allows the sperm to detach from the oviductal epithelium

Increases mobility in thick oviductal fluid and helps propel sperm through outer layers of egg to reach PM

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12
Q

What 3 barriers must be breached for fertilization to occur?

A
  1. The expanded cumulus (corona radiata)
  2. The zona pellucida
  3. The plasma membrane of the egg (oolemma)
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13
Q

The cumulus cell matrix surrounding the egg is predominantly made up of __________, which the sperm can digest via ______

A

Hyaluronic acid

Hyaluronidase

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14
Q

The zona pellucida is made up of what 3 glycoproteins?

A

ZP1
ZP2
ZP3

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15
Q

Sperm contain receptors for which zona pellucida glycoprotein? Binding of receptor to glycoprotein has what effect?

A

ZP3 — binding of ZP3 receptor to ZP3 triggers to acrosome reaction

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16
Q

Describe the acrosomal reaction that occurs when the ZP3 receptor binds the ZP3 glycoprotein

A

Inner sperm plasma membrane fuses with outer acrosomal membrane to release contents of acrosomal vesicle

The enzymes in the acrosomal vesicle digest the zona pellucida

The ZP3 receptor is lost during this time, secondary binding to ZP2 occurs and sperm can enter the holes created in the ZP

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17
Q

Once sperm penetrate the ZP, they can reach the oocyte PM. The exact molecular mechanisms for this are not well understood but it is likely to involve _____ proteins that bind to sperm protein called ______

The entire sperm enters the egg during fusion, and sperm DNA instantly ________. The membrane that forms around it is called the _______

A

Tetraspanin; izumo

Decondenses; pronucleus

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18
Q

What are some examples of assisted reproductive techniques?

A

Ovulation induction

Artificial insemination (AI)

Gamete transfer

In-vitro fertilization (IVF)

Intra-cytoplasmic sperm injection (ICSI)

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19
Q

Fusion of sperm and egg triggers the cortical reaction, characterized by intracellular release of _____ and alteration of ZP2—>______, as well as release of HA and other proteoglycans and proteinases and formation of physical barrier by zona pellucida

A

[Ca]; ZPf

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20
Q

Alteration of ZP2—>ZPf has what effect during the cortical reaction?

A

Blocks binding of additional sperm — preventing polyspermy

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21
Q

Calcium release during the cortical reaction stimulates completion of meiosis II, requiring breakdown of ____ proteins and release of the 2nd polar body

A

MAPK

22
Q

After the cortical reaction, a pronucleus forms around the female chromosomes, and male and female chromosomes repilicate as pronuclei move together. Fusion of pronuclei initiates the first embryonic _______, signifying the beginning of embryonic dev’t

A

Cleavage

23
Q

Timing of pregnancy is classified differently by different professions. What is considered Day 0 for embryologists vs. clinicians?

A

Embryologists = fertilization age — moment of fertilization is day 0

Clinicians = last menses is day 0

24
Q

How is pregnancy divided in embryologists vs. clinicians?

A

Embryologists: corresponds to development — 0-3 weeks is early dev’t, 3-8 weeks is embryonic period, 8 weeks to term is fetal period

Clinicians: trimesters (first tri corresponds to early dev’t, embryonic period, and some of fetal period)

25
Q

How does total gestation time differ based on classification by embryologists vs. clinicians?

A

Embryologists = 38 weeks

Clinicians = 40 weeks

26
Q

During week 1 of embryonic development:

_____ = cell division without growth

The embryo remains ~100 micrometers in diameter. The embryo reaches ~16 cell stage _______ by day 3

The embryo is considered a _____ on day 4

Implantation occurs by day ___-___

A

Cleavage

Morula

Blastocyst

6;8

27
Q

Individual cells during embryonic cleavage are called ______

Mitotic divisions maintain a 2N diploid complement. Cells become ______ and blastomeres are _______

A

Blastomeres

Smaller; totipotent

28
Q

The embryo becomes a 16 cell morula by day 3. The outer cells of the morula increase cell-cell adhesion via ____ and _____, forming the _________.

There is an increase in sodium transport and osmosis to form a ______

A

Desmosomes; tight junctions; trophoectoderm

Blastocele

29
Q

In the later blastocyst, the interior cells will become the ______

A

Inner cell mass

30
Q

The inner cell mass is ______ and will form the ______

A

Pluripotent; embryo proper

31
Q

During what developmental stages does monozygotic twinning occur

A

During cleavage/blastocyst stages

32
Q

Hatching of the embryo from the ZP prior to implantation occurs when _____ secrete proteases that digest the ________

A

Trophoblasts; ZP

[note that inability to hatch can result in infertility, and premature hatching can result in abnormal implantation]

33
Q

Once the blastocyst has hatched, it will begin synthesizing and secreting molecules that promote maintenance of pregnancy, promote implantation, and _____ development

A

Placental

34
Q

Secretion of ______ and ______ factors such as platelet-activating factors, hCG, prostaglandin E2, IL-1a, IL6, etc., occurs after blastocyst hatching

A

Immunosuppressive; immunoregulatory

35
Q

hCG is secreted by _____ and _______ cells. It is measurable in blood ~8 days post ovulation and its structure closely resembles LH

A

Trophoblasts; syncytiotrophoblasts

36
Q

Functions of hCG

A

Prevents involution of the corpus luteum

Prevents menstruation

Leads to increased secretion of progesterone and estrogen

Autocrine growth factor — stimulates trophoblast growth and development; stimulates placental growth

37
Q

The pre-implantation blastocyst is bathed in uterine secretions. It draws ____ and necessary metabolic substances for growth and survival; exchange occurs via ______ and specific transport mechanisms

A

Oxygen; diffusion (O2/CO2)

38
Q

T/F: Just prior to implantation, nutrient exchange becomes inadequate, requiring intimate association via implantation/placental dev’t

A

True

39
Q

Typical implantation occurs where?

A

Posterior wall of uterine fundus

40
Q

Invasive, interstitial implantation involves adhesion supported invasion and migration of ______ cells as well as hydrolytic enzymes which break down the _____

A

Trophoblastic; ECM

41
Q

Attachment of the blastocyst during implantation involves rapidly proliferating __________, initially provides a feeder layer of cintinuously dividing cells

A

Cytotrophoblasts

[so syncytiotrophoblasts have adhesive properties while the cytotrophoblasts have proliferative activity]

42
Q

Syncytiotrophoblasts have adhesive, invasive, and endocrine functions.

Describe some of these functions

A

They express adhesive surface proteins (cadherins and integrins) that initially bind uterine surface epithelia, as the embryo implants bind to components of the uterine extracellular matrix

Breakdown of EC matrix = secretion of matrix metalloproteases

hCG secretion

Highly steroidogenic

Functions in phagocytosis and bidirectional placental transfer

43
Q

What are the stages of implantation?

A

Apposition
Attachment
Invasion
Decidualization

44
Q

Describe the apposition phase of implantation

A

Contact between endometrium and trophoblasts

Typically a crypt in endometrium

Inner cell mass rotation near endometrial epithelium

45
Q

Describe attachment phase of implantation

A

Trophoblast cells adhere to the luminal endometrial epithelium

Interaction between surface proteins on trophoblasts and epithelial cells

Initiates changes in endometrial stroma (decidualization)

46
Q

Describe invasion stage of implantation

A

Degradation of endometrial epithelial cells; trophoblast fusion and formation of syncytiotrophoblasts which protrudes through basement membrane and reaches endometrial stroma

Syncytiotrophoblasts secrete autocrine and paracrine factors to increase invasion/degrade matrix

47
Q

______ is a response of maternal stromal cells to invasion and progesterone, in which endometrial stroma is transformed into enlarged and glycogen-filled decidual cells

A

Decidualization

48
Q

Once decidualization has occurred, the endometrium is called the decidua. It is ready for implantation of the embryo. Describe the functions of the decidua at this point

A

Decidua forms an epithelial like sheet with adhesive junctions that inhibit migration of the implanting embryo

Production of signals that prevents the embryo from invading myometrium — postpartum hemorrhage

49
Q

T/F: a decidual response occurs during ectopic implantation

A

False - there is no decidual response, thus invasion is not controlled and can rupture the tissues and cause hemorrhage

50
Q

Describe the formation of primary, secondary, and tertiary villi during placentation

A

Primary villi form as a result of proliferation of syncytiotrophoblasts and cytotrophoblasts to lacunae

Secondary villi form when mesenchyme cells from extraembryonic mesoderm invade the villi (now called the chorionic membrane)

Eventually, mesenchymal cells form fetal blood vessels de novo = tertiary villi