Dr Kshitiz Murdia, Medical Director, INDIRA IVF group, shares his insights on the importance of embryo implantation for pregnancy
Why is it so difficult for women to become pregnant normally, or even with assistance from the OBGYN? Does it almost feel like the uterus is unconducive towards the implantation of the embryo?
Well, recent research shows that actually might be the case.
Embryo implantation for the beginning of pregnancy is quite similar to a battle. The endometrium is like a ‘fortresses’ that only allows implantation of healthy embryos.
The future of an embryo is undecided before implantation
One of the biggest challenges is the identification of the ‘window of receptivity’ of the endometrium. The period is between three and five days.
- The three steps that assist the implantation of an embryo are as follows –
- The identification of a receptive endometrium
- The recognition of a blastocyst-derived signalling pathway by the epithelium before implantation of the embryo
Reaching of the endometrial layer by the embryo
Damage to the uterine lining assists embryo implantation even when the hormonal priming is absent. It suggests that the epithelial layer of the endometrium acts as a barrier to implantation.
The endometrium allows embryo implantation within the window of receptivity
Only during the receptive window, the endometrium is comparatively hospitable towards the embryo. The morphology of the endometrium changes, complemented by distinct molecular signatures.
Since the receptive window precedes menstruation, a receptive endometrium is similar to injured tissue. A healthy embryo recognises the molecular signatures of a weakened endometrium and seizes the opportunity for implantation.
Embryo implantation changes the structure and nature of the endometrium
The implantation of an embryo elicits molecular signals that change the luminal epithelium structure. The implantation-ready epithelium undergoes cell flattening and a loss of cell polarity. The embryo compacts the edematous stroma of the epithelium and increases the formation of blood vessels.
The morphological changes precede variations in the endometrial gene expression profile. This is followed by the changes in levels of transcription factors, sorting of integrins and distribution of glycans.
The embryo elicits an immune response in the uterus
Embryo implantation results in the activation of the complement pathway and an inflammatory response. The embryo exaggerates the inflammatory response, which can increase the tissue damage in the endometrial epithelium facilitating the trophoblast implantation.
It’s similar to strafing, where the chorionic gonadotropin (CG) and interleukin 1ẞ (IL-1 ẞ) acts like grenades and missiles to wear the inner ‘fortress’ of the endometrium down. Medical professionals leverage the role of CG in assisted reproduction since the intrauterine infusion of the hormone improves the chances of embryo implantation.
Deceit and conviction: that’s how the embryo implants itself
The embryo uses techniques similar to that of the Trojan horse during implantation. It releases extracellular vesicles (EVs) and microRNAs (miRNAs). They seize the cellular machinery necessary for gene expression after the embryo reaches its target.
The epithelium is an “intelligent” opponent that allows implantation and developmentally-competent blastocysts to hijack the machinery. An embryo that secretes the desired type of EVs, miRNAs and other molecular signals can “convince” the endometrium for implantation.
The embryo hijacks the cellular machinery of the endometrial epithelium
After embryo adhesion, it tries to breach the luminal epithelium. It weakens the endometrial wall by downregulating the expression of E-cadherin, the protein that helps endometrial luminal cells adhere to each other tightly.
The trophoblast cells produce proteases that degrade tissues and weaken the endometrial layer.
Recent study suggests that entosis is the likely mechanism embryonic cells use to ‘eat’ the endothelial cells to aid implantation.
The endometrial morphology changes drastically after embryo implantation
After breaching, the embryo transforms the uterus into a new structure – the decidua. It is a remodelled endometrium with the exclusion of material B and T cells, and an influx of specialised NK cells.
Decidualisation is the mandatory morphological change that reprogrammes the endometrial stromal cells into becoming epithelial cells with secretory functions.
The endometrium needs to be able to change its gene expression profile completely for a period. It includes an overhaul of the immune system of the uterus. The ‘weakened’ NK cells and reduced number of B and T cells prevent foetal rejection.
The embryo lowers the defence of the uterine system
The outer cells of the embryo in the trophoblast stage begin to proliferate extensively.
The pioneers of trophoblast invasion include the inner cell mass (ICM), which produces EVs that spearhead the invasion. The decidua assists the invasion by modifying the expression of cell adhesion molecules in the endometrium.
It is evident that once the embryo proves itself worthy, the uterine system lowers its defences.
Endometrium is not a heartless entity: it wants what’s the best for you!
The severe battle between the endometrium and the embryo ensures that the next heir has the best health and ability to survive against all odds.
It is no wonder that the rate of natural pregnancy is only 30 per cent or less. Since gestation is an energetically expensive process for a human, the uterus simply ensures that the toughest embryo wins the fight.
In the cases of repeated miscarriages, it is often seen that the endometrium is incapable of recognising a weak or unhealthy embryo. Conversely, an endometrium may terminate its receptivity towards genetically weak or morphologically inconsistent embryos.
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