Decidualization is a process that results in significant changes to cells of the

endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...

in preparation for, and during, pregnancy. This includes morphological and functional changes (the decidual reaction) to endometrial stromal cells (ESCs), the presence of decidual

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

s (leukocytes), and vascular changes to maternal arteries. The sum of these changes results in the endometrium changing into a structure called the decidua. In humans, the decidua is shed during childbirth. Decidualization plays an important role in promoting placenta formation between a mother and her fetus by mediating the invasiveness of trophoblast cells. It also triggers the production of cellular and molecular factors that result in structural changes, or remodeling, of maternal spiral arteries. Decidualization is required in some mammalian species where embryo implantation and trophoblast cell invasion of the endometrium occurs, also known as

hemochorial placentation Placentation refers to the formation, type and structure, or arrangement of the placenta. The function of placentation is to transfer nutrients, respiratory gases, and water from maternal tissue to a growing embryo, and in some instances to remov ...

. This allows maternal blood to come into direct contact with the fetal chorion, a membrane between the fetal and maternal tissues, and allows for nutrient and gas exchange. However, decidualization-like reactions have also been observed in some species that don't display hemochorial placentation. In humans, decidualization occurs after ovulation during the

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

. After implantation of the embryo, the decidua further develops to mediate the process of placentation. In the event no embryo is implanted, the decidualized endometrial lining is shed or, as is the case with species that follow the estrous cycle, absorbed. In menstruating species, decidualization is spontaneous and occurs as a result of maternal hormones. In non-menstruating species, decidualization is non-spontaneous, meaning it only happens after there are external signals from an implanted embryo.

Overview

After ovulation, the high levels of

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

initiate the molecular changes leading to decidualization. The process triggers an influx of decidual leukocytes along with morphological and functional changes of ESCs. The changes in the ESCs result in the endometrium developing a secretory lining that produces a variety of proteins, cytokines, and growth factors. These secreted factors will regulate the invasiveness of trophoblast cells that eventually form the placental connection if an embryo implants into the decidua.

Decidual leukocytes

One of the identifying features of the decidua is the presence of large numbers of leukocytes that are mostly made up of specialized uterine natural killer (uNK) cells and some

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s. As the fetus consists of both maternal and paternal DNA, the decidual leukocytes play a role in suppressing the immune response of the mother to prevent treating the fetus as genetically foreign. Outside of their immune functions, the uNK cells and dendritic cells also act as regulators of maternal spiral artery remodeling and ESC differentiation.

Endometrial stromal cells (ESCs)

ESCs are the connective tissue cells of the endometrium that are fibroblastic in appearance. However, decidualization causes them to swell up and adopt an epithelial cell-like appearance due to the accumulation of

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

and lipid droplets. Furthermore, they begin secreting cytokines, growth factors, and proteins like IGFBP1 and prolactin, along with extracellular matrix (ECM) proteins such as fibronectin and laminin. The increased production of these ECM proteins turns the endometrium into the dense structure known as the decidua, which produces factors that promote trophoblast attachment and inhibit overly aggressive invasion.

During pregnancy

The decidual reaction is seen in very early pregnancy in the generalized area where the

blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the t ...

contacts the endometrial decidua. It consists of an increase in secretory functions of the endometrium at the area of implantation, as well as a surrounding stroma that becomes

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

tous. The decidual reaction occurs only in humans and a few other species. The decidual reaction and decidua are not required for implantation. Evidence can be taken from the fact that in ectopic pregnancies and hysterectomies, implantation can occur anywhere in the abdomino-pelvic cavity.

Role in diseases and disorders

Abnormalities in decidualization have been implicated in diseases such as

endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...

, in which impaired decidualization leads to ectopic uterine tissue growth. Lack of decidualization has also been linked to higher rates of

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...

. Chronic deciduitis, a chronic inflammation of the decidua, has been linked with premature birth.

In research

The decidualization process is initiated by progesterone, but this requires cyclic adenosine monophosphate (cAMP) to act as the initial signalling molecule to sensitize endometrial cells to progesterone. Consequently, human ESCs have been decidualized in culture with chemical analogs of cAMP and progesterone together. '' In vitro'' decidualization results in similar morphological changes to the human ESCs as well as upregulated production of decidualization markers such as IGFBP1 and prolactin. Mouse models have been extensively used for the identification of the molecular factors required for and involved in decidualization.

References

External links

Implantation stages
Human embryology; developed by the universities of Fribourg, Lausanne and Bern (Switzerland).
Histopathology Uterus – Decidual reaction
Microscopic review of decidualization {{Embryology Human pregnancy Menstrual cycle