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Repro 313 > Lecture 9; Fertilisation and Implantation > Flashcards

Lecture 9; Fertilisation and Implantation Flashcards

1
Q

Describe ejaculate composition

A
  • Sperm leaves the male reproductive tract bathed in seminal plasma. (unmixed)
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2
Q

What happens when seminal plasma mixes?

A

As prostatic and seminal fluids mix in the vagina, a coagulum forms that holds ejaculate together and adheres the ejaculate to the female reproductive tract

(~1minute) (vaginal insemination)

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3
Q

What happens after vaginal insemination and coagulate formation?

A

Within 15 mins of ejaculation the coagulum is dispersed (lots of proteases in seminal fluid) allowing individual sperm to begin their quest for an egg

(breakdown of coagulum = liquefaction) Allows sperm motility

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4
Q

How does the vaginal environment make it difficult for sperm?

A

pH of the vagina is ~4.2pH and this pH is inhibitory to sperm motility and survival.

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5
Q

How does ejaculate counter vaginal pH?

A

Seminal plasma buffers the vaginal pH to ~7.2 at this pH sperm can become motile.

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6
Q

Describe where sperm must migrate to and from in the female reproductive tract;

A

Sperm must migrate from the site they are deposited to the oviduct for fertilisation to occur.

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7
Q

What is the first barrier in sperm transport?

A

The first barrier in sperm transport is the cervix.

The cervix secrete a mucous whose characteristics are under hormonal control and change throughout the menstrual cycle

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8
Q

How does timing matter with cervical mucous and sperm movement?

A

There is a short window (peri-ovulation) around the time of ovulation where sperm can pass through the mucous. Otherwise cervical mucous is hostile to sperm transport.

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9
Q

Describe cervical mucous during peri-ovulation

A

During peri-ovulation cervical mucous is produced in large amounts and it is thin.

Fertile mucous aligns its fibres and allows the passage of sperm through columns through the cervix (normally cross fibres = barrier)

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10
Q

What speed to sperm move through the cervix?

A

Sperm move through the cervix at a speed of around 1.2-3mm/minute

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11
Q

How does cervical mucous filter poor sperm?

A

The tails of normal sperm cause the fibres of the cervical mucus to vibrate in rhythm and breakdown.

Failure of abnormal sperm to induce this vibration in the cervical mucous may retard the progress of abnormal sperm

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12
Q

How many sperm are in ejaculate and how many reach the uterus?

A
  • Up to 20million sperm in ejaculate and 1million enter the uterus.
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13
Q

Do all sperm immediately traverse the cervix?

A
  • Not all sperm traverse the cervix immediately, some are stored in the crypts of the cervix which from they may later move into the uterus
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14
Q

What happens to sperm once they have traversed the cervix?

A

After traversing the cervix sperm move to the utero-tubal junction in about 30 minutes.

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15
Q

Describe the rate of sperm movement and the implications of discrepancies;

A

Sperm advance at 3mm/minute because of tail beating. This does not account for the distance covered in 30 minutes.

Therefore muscular contractions must be important in trans-uterine transport

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16
Q

What may cause uterine contractions to aid sperm movement?

A

Stimulation of the cervix by the penis may cause the release of oxytocin from the pituitary which then causes rhythmic uterine contractions aiding sperm.

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17
Q

What does sperm arriving in the uterus cause?

A

Sperm produce an innate immune response

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18
Q

Describe the innate immune response;

A

Sperm arriving in the uterus induce an infiltration of leukocytes (leukocytosis)

These phagocytose dead or dying sperm

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19
Q

Why else may an innate immune response be important?

A

Exposure of the maternal immune system may be important in dampening down or tolerising maternal immune response to paternal antigens

e.g women who have unprotected sex with a single partner for more than a year before becoming pregnant are at less risk of developing pre-eclampsia

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20
Q

Whats the implication of producing only one egg during ovulation?

A

Half the sperm will arrive at the utero-tubal junction on the wrong side!!!

They will continue their fruitless journey along a fallopian tube that has no egg

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21
Q

Describe sperm movement in the fallopian tube and numbers;

A

Sperm enter the follopian tube and movement is very slow

Only a few hundred will reach the distal end of the follopian tube

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22
Q

What happens if sperm enters the follopian tube prior to ovulation?

A

If sperm enter the follopian tube prior to ovulation their rate of tail beating slows and they wait in the narrow isthmus of the tube.

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23
Q

What happens to sperm during ovulation?

A

They move up the egg and stored sperm may also be released from the crypts of the cervix.

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24
Q

Where does fertilisation occur?

A

The ovum is usually fertilised close to the junction of the isthmus and the ampulla of the fallopian tube.

If unfertilised the oocyte can last 24hrs or less

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25
Q

What happens when sperm miss their target?

A

The continue up the fallopian tubes and enter the abdominal cavity

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26
Q

How long can sperm survive in the female reproductive tract?

A

Sperm usually only survive in the female reproductive tract only for a few ays but there are rare case reports of much longer survival times (up to a few months)

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27
Q

what is the first reaction of the sperm in the female reproductive tract?

A

Capacitation

Occurs a few seconds after ejaculation

28
Q

What is capacitation?

A

The process whereby sperm in the female reproductive tract can the ability to fertilise the ovum

29
Q

Describe the cellular events that happen in capactitation;

A

Rapid capacitation events;

HCO3- and Ca2+ activate:
- Soluble Adenyl Cyclase (SACY)

SACY activates PKA, increasing membrane solubility to Ca and thus ICF Ca concentrations

Slow Capacitation events;

Removal of Cholesterol in the membrane. Allowing sperm to maintain high levels of HCO3.

30
Q

What do capacitated sperm show?

A

Capacitated sperm show hyperactivation in which the tail movements changes with an increased bending of the tail and swinging of the head.

31
Q

What may hyperactivation facilitate?

A

Hyperactivation may facilitate movement of sperm through the tortuous folds of the follopian tubes.

32
Q

What is the length of time for capacitation?

A

The length of time for capacitation of human sperm is variable but only capacitated sperm can undergo the acrosome reaction.

33
Q

Describe ovulation;

A

Ovum release is a gradual gentle process that takes 30 seconds. Not an explosion!

34
Q

What is the function of the cumulus cells?

A

Cumulus cells act like velcro for fibria to have grip and sweep the ovum up.

If they are not present it is unlikely that the ovum will be swept up

35
Q

How does the follopian tubes move the ovum?

A

Combination of fibria beating and peristaltic contractions

36
Q

What is the first step in fertilisation?

A

The sperm penetrates the surrounding cumulus cells.

Assisted by hyaluronidase secreted by the acrosome. This digests the basement membrane allowing sperm to squeeze b/w cumulus cells

37
Q

What stimulates the hyaluronidase release in step one?

A

Stimulated by progesterone in the fluid surrounding the oocyte.

Only partial release of acrosome products

38
Q

What is step two in fertilisation?

A

Sperm digests through the corona radiata and contacts the zona pelucida. This contact triggers the acrosome reaction

39
Q

Describe the zone pelucide proteins that are involved in initiating the acrosome reaction;

A

Zona pelucida = protein coat

Major proteins= ZP 1 , 2 , 3

ZP 3 = primary sperm receptor (contact with sperm ligand initiates the acrosome reaction completely)

Sperm ligand is unknown (other receptor/ligand pairs may be involved)

40
Q

What is the acrosome?

A

The acrosome is a membranous pouch containing proteinases and other enzymes such as hyaluronidase

41
Q

Describe the acrosome reaction;

A
  • Acrosomal and plasma membranes of sperm head fuse. Thus allowing release of the acrosomal contents to the environment around the sperm
  • Acrosome reaction triggered by Ca infux
  • Progesterone or ZP3 can trigger this Ca influx
42
Q

In vitro how can the acrosome reaction be triggered?

A

Using a Ca ionophore

43
Q

Whats a requirement for fertilisation and acrosome reaction?

A

The acrosome reaction must occur in close proximity to the oocyte for a sperm to be able to fertilise it naturally

About 10% of sperm spontaneously undergo the acrosome reaction distal to the oocyte and these sperm cannot fertilise the egg.

44
Q

What is step three in the acrosome reaction?

A

Aided by enzymes of the acrosome the sperm then penetrates through the zona pellucida to the pervitelline space

  • ~10mins
45
Q

Once sperm enters the vitelline space what happens? (part of step 3)

A
  • Sperm then attatches to the vetilline membrane and the two membranes fuse allowing the sperm nucleus to enter the ovum
46
Q

What else happens as the sperm enters the vitelline space?

A

As sperm enters the vitelline membrane granules are released by the ovum (cortical granules) that prevent further sperm penertrating the zona

may include anti-acrosin

47
Q

Describe fertilisation beyond the third step;

A
  • Entry of sperm into the oocyte causes a release of intracellular Ca, this is followed by regular spikes of Ca in the oocytes.
  • These Ca changes alter protein phosphorylation patterns in the oocyte and the oocyte nucleus becomes activated
  • oocyte nucleolus completes the second mitotic division
  • oocyte forms a pronucleus as does the sperm
  • Two membranes of the pronuclei then break down and mitotic division begins. The fertilised egg is now a zygote.
48
Q

Describe movement of the zygote from the follopian isthmus

A

The zygote begins cleavage in the tube and takes 5 days to transverse and enter the uterus. (during the passage, 2 then 4 cell products of conception form)

Further doubling gives rise to the morula at the 8-16 cell stage. The cells of the morula become tightly cohesive and compact

49
Q

What is gestation age?

A

Age of foetus from ovulation onwards

50
Q

What is a 64 cell product?

A

Blastocyst (comes after morula)

51
Q

Describe the blastocyst

A

Blastocyst;
- Two differentiated cell populations: trophectoderm (forms placenta) and inner cell mass with will form the embryo proper

Blastocyst remains free in the uterine cavity 2-3 days before implanting

52
Q

What is decidualisation?

A

Endometrial cells differentiate to facilitate pregnancy;

  • stromal cells become plump and glycogen rich
  • Recruitment of leukocytes

This starts during the menstural cycle. (not all animals are decidual)

53
Q

Describe when implantation normally occurs

A

Implantation usually occurs 7-10 days post ovulation

The blastocyst remains encompassed by the zona pelucida while free floating in the uterine cavity

54
Q

Describe the blastocyst adhering to the uterine wall (first part of implantation)

A

The hatched blastocyst comes into contact with the receptive decidua

The blastocyst sticks to the decidual epithelium via specific adhesion molecules . This is called nidation

55
Q

Following nidation what happens

A

The embryo erodes the uterine wall and becomes completely embedded the epithelium heals over the implantation site.

The trophoectoderm differentiates into two populations;

  • mononuclear cytotrophoblasts
  • multinucleated syncyotiotrophoblasts
56
Q

Describe the placenta;

A
  • The placenta has a branching villous structure
  • The placenta is made of specialised cells called trophoblasts
  • 3 main populations of trophoblasts
    • Cytotrophoblasts
    • Syncytiotrophoblast
    • Extravillous trophoblast (EVTs)
57
Q

Describe cyotrophoblast function;

A

Cytotrophoblasts are the pre-cursors for both syncytiotrophoblast and EVTs

58
Q

Describe syncytiotrophoblast;

A

The syncytiotrophoblast is a continuous single (multinucleated) cell formed by fusion from underlying cytotrophoblasts

59
Q

Describe EVTs

A

IN villous tips cytotrophoblasts differentiate into EVTs that break through the overlying syncytiotrophoblast and grow out from the placenta by invading into the decidual stroma.

60
Q

Describe EVT’s movement and implantation

A

EVTs invade the decidua in columns and also spread outwards from the nidation site invading into the decidua

61
Q

What us the function of EVTs invading the decidua?

A

1) Physical attatchment of the placenta to the decidua

2) Adaptation of blood vessels in the uterus called the spiral arteries to maintain pregnancy

62
Q

Describe EVT movement with regard to the spiral arteries;

A

EVTs migrate down the spiral arteries and replace the endothelial cells that line these arteries. They also digest the muscular/elastic wall of these vessels and transform them into

  • non-vasoactive
  • flaccid
  • wide bore tubes, no muscular walls, lined by trophoblasts

Traditionally called the physiological changes of pregnancy more commonly referred to as spiral artery remodelling

63
Q

What does spiral artery remodelling allow and what sort of process is it?

A

This means the placenta and fetus can get a constant and increased supply of blood as they grow.

Constant perfusion

These processes are highly regulated both spatially and temporally

64
Q

What are trophoblast plugs and their function?

A

During the first trimester EVTs form plugs in the spiral arteries so that little maternal blood reaches the placenta.

The trophoblast plugs act as a pressure reducing valves that stop the implanting placenta being exposed to the full force of the maternal blood pressure. (early exposure increases risk of miscarriage)

65
Q

Describe early embyronic nutrition;

A

In the absence of maternal blood the embryo is nourished by;

1) Glandular secretions (stored in yolk sac)
2) Yolk sac

Repro 313 (20 decks)

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