What is endometrial decidualization?
Endometrial decidualization is one of the first changes that happen in the very early stage of a pregnancy. It’s a complex process of the endometrium transforming itself to create the optimal microenvironment for the tiny embryo to implant and develop in the uterus. Encompassing biochemical, physiological and functional changes at multiple levels, endometrial decidualization lays the foundation for the normal development of the baby, as well as the maintenance of a healthy pregnancy.
How does endometrium change to accept and nurture the embryo?
Endometrium – the lining of the uterus – consists of multiple layers. The surface is covered in a single layer of epithelium cells (the dark purple cells that line the white space - uterine glands - in the photo) and basal lamina, which is supported by a cell-rich connective tissue called stroma cells (in the photo, these are the pink cells that fills the space in between the uterine glands). A network of blood vessels supply oxygen and nutrients to the stroma cells.
Endometrial decidualization is governed by multiple pathways, invloving hormones (primarily progesterone and estrogen, two important reproductive hormones that work synergistically), cytokines and transcription factors. During endometrial decidualization, a few things happen:
- First, the mucous membrane of the endometrium increases in thickness and vascularity. The increased development of blood vessels ensure that the implanting embryo – and the supportive structures like the placenta - will have adequate supply of oxygen and nutrients.
- Secondly, the stroma cells transform themselves into decidual stroma cells. Decidual stroma cells accumulate glycogen, lipids and proteins within the cytoplasm (the fluid inside cells), which become the nutrient source for the implanting embryo. There is also emerging evidence that recruitment and differentiation of immune cells occur during endometrial decidualization.
- Once the embryo implants, its trophoblast cells (the cells that form the outer layer of the blastocyst) proliferate and enter the endometrium, facilitating the vascular development in the decidual cell layer and maintenance of the endometrial decidualization. If no embryo implants in the cycle, endometrial decidualization stops and the cells are shed in a menstrual period.
How does endometrial decidualization impact pregnancy?
Proper decidualization ensures endometrial receptivity and facilitates implantation and further development of embryos in multiple ways:
- Penetration of the endometrium by embryonic cells
- Promotion of vascular development and placenta formation
- Intrauterine development of the embryo
- Differentiation of immune cells, which helps the maternal immune system accommodate the embryo (despite the embryo being 50% paternal, foreign to the maternal immune system)
When decidualization doesn’t progress properly, complications can arise:
- Recurrent miscarriages, especially early miscarriages
- Recurrent implantation failure
- Intrauterine growth restriction
What is the possible role of DHEA in endometrial decidualization and endometrial receptivity?
In the last few years, multiple studies have suggested that DHEA (dehydroepiandrosterone), a precursor to testosterone and estrogen, may play an important role in endometrial decidualization and its receptivity toward implanting embryos.
Progesterone and estrogen regulates endometrial decidualization together
To understand the possible role of DHEA in endometrial decidualization, we need to go back a few steps. While other factors such as cytokines and transcription factors are involved in this complex process, the two major players are progesterone and estrogen. These two hormones work in tight balance to regulate what happens to the endometrial cells in different phases of the menstrual cycle:
- Progesterone promotes the expression of estrogen receptors on the stroma cells.
- Once estrogen binds to the estrogen receptors, it promotes the proliferation of the endometrial stroma cells during the proliferative phase of the menstrual cycle.
- In the next phase – secretory phase – of the cycle, progesterone then inhibits the estrogen functions to let the stroma cells start the process of decidualization.
DHEA may support decidualization through conversion into testosterone and estrogen
One of these hormones – estrogen – is synthesized in the body from androgens. Endometrium produces its own androgen (testosterone), using DHEA. Conversion of DHEA into testosterone has been found to vary depending on the menstrual cycle phase. This conversion is the most active during the secretory phase, when endometrial decidualization occurs, suggesting that the cellular need for androgens is the most acute in this phase.
While scientists don’t know exactly what functions androgens play in the decidualization process, we know that endometrial stroma cells also have androgen receptors. This also points to the strong possibility that androgens are necessary for the process, whether indirectly through conversion into estrogen or directly through the androgen receptors. This is supported by a study that found reduced markers of endometrial receptivity when androgen receptors were blocked.
Interestingly, in 2017, a study found that DHEA supplementation improved the expression of HOXA-10 mRNA in the endometrium among women with poor response to IVF medications. HOXA-10 is a factor known to be involved in endometrial decidualization.
A 2018 study also found that addition of DHEA enhanced endometrial decidualization in women in their 40s. Authors hypothesized that supplementation with DHEA may enhance intracellular production of androgens in the endometrium, thus promoting the endometrial decidualization process.
Should I take DHEA to improve endometrial receptivity?
While this is an exciting area of reproductive research, and the theoretical connection between DHEA and endometrial receptivity is enticing, the jury is still out. More research is needed to confirm that DHEA benefits endometrial receptivity, as well as to understand the mechanism of action and the optimal DHEA dosage for supporting endometrial decidualization. We also don’t know who benefits from DHEA in this regard.
The bottom line: If you are taking DHEA for ovarian reserve support, it may come with a bonus benefit in the form of the endometrium being better prepared to welcome the implanting embryo. But it may be too early to start taking DHEA for endometrial receptivity specifically.
As always, we strongly recommend everyone considering DHEA supplementation for fertility purposes to discuss it with a qualified healthcare provider first. If you – or your healthcare team – have any questions, please let us know via LiveChat. We are with you.