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Fetus > Molecular aspects of implantation > Flashcards

Molecular aspects of implantation Flashcards

1
Q

How does the endometrium change throughout the menstrual cycle

A

Proliferative phase- small glands with epithelial cells close together + overlapping, dense stroma
Early secretory phase- glands expanding, secretory vesicles at basal side of epithelial cells
Mid secretory phase- Further expansion of glands with secretory vesicles at apical side of epithelial cells, presence of secreted material in lumen
Late secretory phase- long extended glands with no secretory vesicles, oedema in stroma

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2
Q

How does steroid hormone receptor expression change

A

Expressed in the nuclei of both stromal and epithelial cells
Oestrogen receptor- maximum expression in late proliferative/early secretory phase
Progesterone receptor- maximum expression in early secretory phase. Decreases in epithelial cells before stromal cells

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3
Q

What immune cells are present in the endometrium

A 
Leucocytes
uNK cells (CD56+ve)
Macrophages
T cells
NO B cells
there are changes in the populations during early pregnancy
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4
Q

How is the endometrial cycle times

A

From the last menstrual period
According to the LH surge (tripling)
From endometrial morphology

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5
Q

What is the window of implantation

A

Day 20-23 of the endometrial cycle when the endometrium is receptive to an embryo
Characterised by expression of specific set of factors and pinopode formation

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6
Q

What are the abnormalities of endometrial function

A

Recurrent implantation failure after IVF- failure to achieve pregnancy after transfer of good quality embryos
Recurrent miscarriage- implantation occurs but pregnancy lost due to abnormal placental formation

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7
Q

Describe implantation

A

Initial interaction between trophoblast and luminal epithelium
Later interactions between trophoblast and stroma

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8
Q

What is the villous trophoblast, endovascular trophoblast and syncytiotrophoblast

A

Villous- Invasive, contacts maternal stroma, anchoring
Endovascular- invades maternal blood vessels
Syncytiotrophoblast- formed inside maternal blood vessels by cell fusion

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9
Q

Describe decidualisation

A

After implantation
Stromal cells secrete many factors including prolactin + IGFBP1
Controlled by cAMP and progesterone

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10
Q

What molecules are involved in the control of implantation

A

Proteases
Adhesion molecules/integrins
Cytokines
MMPs

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11
Q

How are MMPs produced

A

Secreted in inactive form containing propeptide, activated by removing
Expression of protein increased by cytokines IL1 + TNFa
Activation by trypsin and plasmin
Inhibited by TIMPs

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12
Q

What controls endometrial MMP production

A

Progesterone decreases production

IL1 and TNF increase production

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13
Q

What controls trophoblast MMP production

A

Hormones eg. hCG + progesterone

Cytokes eg IL1, TNF, IL6

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14
Q

What are the roles of proteases in endometrial function

A

Implantation- breakdown of extracellular matrix to allow embryo through epithelial cells
Menstruation- breakdown of endometrial tissues

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15
Q

What is the function of integrins

A

Mediate cell binding to ECM
Transduce signals from ECM into cells
Regulate gene expression including ECM degrading enzymes
avb3 may be involved in attachment of embryo to endometrium

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16
Q

What is the expression pattern of endometrial integrins throughout cycle

A

avb1, a1, a4 cyclically expressed

Upregulation during window of implantation

17
Q

Describe expression of integrins during window of implantation

A

Highest expression in epithelium and blood vessels
avb3 expressed in luminal + glandular epithelium equally
a1 + a4 higher in glandular than luminal epithelium

18
Q

Describe integrin expression in women with reproductive failure

A

Abnormal expression of avb3 in women with infertility
No difference in avb3, a1 or a4 in women with recurrent miscarriage or RIF
Levels not predictive of pregnancy outcome

19
Q

What cytokines are produced by the endometrium

A 
Pro-inflammatory
Th1 (IL2, TNFa, IFNy) and Th2 (IL10, IL4)
TGFb
GM-CSF, CSF
IL12, IL18, IL15
20
Q

What are the proinflammatory cytokines

A

IL1, TNFa, IFNy, LIF, IL11, IL6

21
Q

How are cytokines expressed in the endometrium

A

Mainly by epithelial cells in nonpregnant endometrium

By decidual and epithelial cells after implantation

22
Q

How does cytokine expression change after implantation

A

Many cytokines increased

23
Q

Describe rodent studies on Th1 an Th2 cytokines

A

Normal pregnancy outcomes- low placental production of IL2, IFNy + TNFa, produce low levels when challenges. Injection of IL10, IFNy + TNFa increases abortion rate
Abortion prone mice- Higher production of IL2, IFNy + TNFa. Produce higher levels when challenged. Injection of IL10 decreases abortion rate

24
Q

Describe the evidence for the role of LIF and IL11 in implantation

A

LIF- implantation does not occur in LIF knockout mice. LIF negative blastocysts in normal mice results in pregnancy- endometrial not embyronic LIF necessary. Provides model of infertility
IL11- IL11Ra knockout mice have implantation but only small decidua that degrades causing pregnancy loss. model of recurrent miscarriage

25
Q

Describe LIF and IL11 production in women with RIF + RM

A

RIF- decreased expression of LIF in glandular epithelium

RM- decreased endometrial expression of IL11 but not its receptor

26
Q

What is the role of cytokines in implantation

A

Receptors expressed by cytotrophoblast cells
Bring about positive (secretory) effects and negative (apoptosis) effects on cytotrophoblast cels
Possibly affect leucocyte activity particularly uNK cells

27
Q

What is the function of endometrial transcriptomics

A

Microarray based
Allows monitoring of 1000s of genes
Comparison of gene expression during different periods of menstrual cycle, and different pathologies
Identification of genes specifically expressed in window of implantation

28
Q

What is an endometrial receptivity array

A

Molecular tool defining receptivity at LH +7 (natural) or P+5 (hormone replacement)
Array of 238 genes
Used to determine receptivity status of endometrium in women undergoing IVF
Personalised treatment- if prereceptive then transfer delayed

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