Implantation

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Implantation Prof Aboubakr Elnashar Benha University Hospital, Egypt Aboubakr Elnashar

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implantation

Transcript of Implantation

Page 1: Implantation

Implantation Prof Aboubakr Elnashar

Benha University Hospital, Egypt Aboubakr Elnashar

Page 2: Implantation

Introduction Blastocyst

a preimplantation embryo of varying cell number, from

30 to 200

Formed

4 days after the gonadotropin surge

3 days after ovulation,

Implantation

embedding of the blastocyst in the endometrial

stroma

begins with the loss of the zona pellucida (hatching)

1-3 days after the morula (8 cells) enters uterine

cavity.

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Preparation for Implantation

I. The change from proliferative to secretory

endometrium

At the time of implantation

The endometrium is 10-14 mm thick

Secretory activity has reached a peak

This change is the histologic expression of many

biochemical and molecular events.

{The primary endocrine requirement is the presence of

progesterone}.

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II. Endometrial receptivity

heralded by the progesterone-

induced formation of pinopodes

pinopodes absorb fluid from the

uterine cavity forcing the

blastocyst to be in contact with

the endometrial epithelium.

The window of endometrial

receptivity: 20-24 of a 28-day

normal cycle.

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III. A dialogue between endometrium and the early

embryo.

1. Early pregnancy factor (EPF)

detected in the maternal circulation within 1-2 days

after fertilization.

prior to implantation is produced by the ovary in

response to a signal from the embryo.

After implantation is derived from the embryo.

has immunosuppressive properties

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2. HCG

Secreted by blastocysts

beginning days 7-8 after fertilization

enhancing steroid secretion from corpus luteum

3. Prostaglandin E2

Secreted by secretory endometrial epithelial cells

synthesis is increased at the implantation site

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Implantation Define:

process by which an embryo attaches to the uterine

wall and penetrates first the epithelium and then the

circulatory system of the mother to form the placenta.

It is a process that is limited in both time and space.

Timing:

2-3 days after the fertilized egg enters the uterus;

entry is on day 18 or 19 of the cycle.

5-7 days after fertilization.

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First hormonal evidence of implantation

(the appearance of hCG)

occurred on 8, 9, or 10 days after ovulation

the earliest was 6 days and the latest 12 days.

The risk of spontaneous early miscarriage markedly

increases with late implantations (later than 9 days

after ovulation).

Stages:

Apposition,

Adhesion, and

Invasion (also called migration to denote its benign

nature).

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I. Apposition The human blastocyst remains in the uterine

secretions for approximately 1 to 3 days and then

hatches from its zona pellucida in preparation for

attachment.

The implantation site:

usually in the upper, posterior wall in the mid sagittal

plane.

Apposition of the blastocyst to the uterine epithelium,

usually about 2-4 days after the morula enters the

uterine cavity.

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The endometrium produces at least 3 cytokines

involved in implantation.

1. colony-stimulating factor-1 (CSF-1)

2. leukemia-inhibitory factor (LIF)

3. interleukin-1 (IL-1).

LIF displays the same pattern of expression as

CSF-1

Blocking the interleukin-1 receptor in mice: prevents

implantation.

Role of interleukin-1 is less clear

{mice that are deficient in the interleukin receptor have

normal reproduction}.

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II. Adhesion:

{integrin binding}

Peak integrin expression at the time of implantation

Abnormal level of integrin expression may be a

cause of infertility .

Formation of junctional complexes prevents

dislodging the embryo by flushing.

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III. Invasion

{invasion of the trophoblast via degradation of the

extracellular matrix}.

Three subsequent interactions occur:

1. Trophoblasts intrude between the uterine

epithelial cells.

2. Epithelial cells are lifted off the basement

membrane; trophoblasts can interdigitate

underneath.

3. Fusion of trophoblast with the uterine epithelial

cells.

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Process is not destructive.

Embryo does contain proteases, but protease

activity is confined to the removal of dead cells .

Cells move away from the trophoblast: contact

inhibition.

Trophoblast fills the spaces left

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Regulation

Many growth factors and cyto­kines

1. Integrin expression is critical to the early invasion

of the trnphohlast

2. Laminin: Actively migrating cells preferentially-

bind laminin

3. Fibronectin

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Vascular changes

uterine spiral arterioles are invaded by

cytotrophoblasts.

Maternal endothelium is replaced by

cytotro­phoblast tissue as far as the first third of the

myometrium.

This replacement may be governed by the selectin

family of surface molecules.

Failure of this process is noted in preeclampsia.

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Matrix metalloproteinases . Involved in menstruation.

key players in matrix degradation during the

trophoblast invasion.

Include the following:

Collagenases.

Gelatinases.

Stromelysins.

Can be activated by integrin-mediated adhesion.

Production is regulated by the following:

Plasminogen activators.

Cytokines.

Tissue inhibitors (TIMPs).

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Limitation of invasion .

Invasion is mediated by

Serine proteases and

Metalloproteinases (plasminogen activators):

plasmin activator metalloproteinase family, blast

plasminogen activator receptor may control the

plasmin proteolysis.

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Mechanisms of limitation

1. Cytokine secretion from the endometrial

lymphocytes (including natural killer cells) may

limit the invasion.

2. Invasion is limited by the decidual cell layer

Histamine may initiate the decidual response.

Blockage of histamine receptor H1 and H2 may

decrease the rate of implantation.

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3. Plasminogen activator inhibitor-I (PAl-I) is the

major decidual cell product; binds the plasminogen

activator

4. Transforming growth factor-β (TGF- β) is the key

growth factor in limiting invasion.

Induces increase in both PAl-l and TIMP.

Inhibits integrin expression.

Influences cytotrophoblasts to differentiate into

noninvasive syncytiotrophoblasts.

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Key Steps in Implantation The early embryo enters the uterine cavity as an 8-

cell morula and becomes a 30 to 200-cell blastocyst

before implantation.

Hatching from the zona pellucida begins about 1-3

days after the morula entered the uterine cavity.

The endometrium is prepared for implantation by the

complex activity of cytokines, growth factors, and lipids

modulated by the sex hormones, especially

progesterone.

The endometrium is receptive for implantation for only

a few days.

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The process of implantation begins with apposition

and adhesion of the blastocyst to the uterine

epithelium, about 2-4 days after the morula enters the

uterine cavity.

This process is mediated by cytokines and involves

adhesion molecules (integrins) that interact with

extracellular components, especially laminin and

fibronectin.

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Trophoblastic invasion rapidly follows adhesion of the

blastocyst, mediated by proteinase degradation of the

extracellular matrix.

The placenta is formed in the second week after

ovulation.

Limitation of trophoblastic invasion is due to a

restraint imposed by proteinase inhibitors, especially

plasminogen activator inhibitor and tissue inhibitors of

metalloproteinases.

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Thank you Aboubakr Elnashar