Understanding how the uterine lining works

The uterine lining is called the endometrium. The endometrium has two important parts. The basal layer is the bottom layer closest to the muscle of the uterus. The basal layer always remains in the uterus even after a woman has her period every month. The basal layer does not grow or change in response to hormones. Most importantly, the basal layer contains many of the stem cells which are necessary to regenerate the uterine lining every month.

The functional layer is located on top of the basal layer. This layer grows and changes in response to hormones. These changes are mandatory in order to allow an embryo to implant. In the absence of pregnancy, it is the functional layer that is shed every month when a woman has her period.


After ovulation, the ovary produces progesterone. Progesterone (along with a slew of other molecules and growth factors) changes the uterine lining so that an embryo is able to implant. In the first several days after ovulation, the changes in the uterine lining are called secretory changes. After several days, there are further changes which are called decidual changes. The entire process is known as decidualization.

Much has been learned about the process of decidualization in the last few years. It is now believed that defects in the process of decidualization may cause infertility, miscarriage and other complications of pregnancy.

Important cells for decidualization

Once group of cells found in the functional layer of the endometrium are called endometrial stromal cells (EnDC). Progesterone (and other factors) change the EnDC into decidual cells (DC). However, not all of the EnDC cells will become decidual cells. Some may instead develop into a different cell type that doesn’t allow for healthy embryo implantation. These “bad” cells are acute senescent decidual cells (sometimes referred to as SASP). Senescent cells do not respond to progesterone and are responsible for the shedding of the lining each month.

How does the uterine lining become “healthy”?

In seems that healthy decidualization starts with the uterine lining regenerating itself normally after a woman has her period. The EnDC must be replenished and, after ovulation, they must be converted to decidual cells (DC) instead of senescent cells.

Cells in the basal layer called Endometrial Mesenchymal Stem-Like Progenitor Cells (eMSC) are primarily responsible for replenishing the EnDC. However, recent evidence has now pointed to another important source of stem cells to help replenish the uterine lining. These cells come from the bone marrow!

The Important Role of Bone Marrow

Inside of your bones are stem cells that are important for replenishing many different kinds of cells. Most people are aware that the bone marrow is the source of blood cells. Some of the bone marrow stem cells also make other types of cells (not blood cells). The cells are called bone marrow derived cells (BMDC). It now appears that BMDC are important for forming and maintaining a uterine lining that has healthy decidualization.

How does the uterus communicate with the bone marrow?

Estrogen from the ovaries causes the uterine lining to thicken and causes the production of a growth factor called SDF-1. SDF-1 causes the bone marrow to release BMDC and draws those BMDC to the basal layer of the endometrium. While there, the BMDC change into eMSC which replenish the EnDC and promote the formation of decidual cells instead of senescent cells.

How can this help me have a baby?

Doctors may be able to manipulate this system with medications to help women gain a healthier uterine lining and improve decidualization.

For example, studies have found that women with recurrent miscarriage have low levels of eMSC in the basal layer and have an excessive amount of senescent cells compared to decidual cells after ovulation.

One recent study used a diabetes medication called sitagliptin in women with recurrent miscarriage and found that it increased the amount of eMSC and improved the ratio of healthy decidual cells compared to senescent cells. It also appeared to reduce the risk of miscarriage.