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

endometrium The endometrium is the inner epithelium, 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 funct ...

in preparation for, and during,

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

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

white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

s (leukocytes), and vascular changes to maternal arteries. The sum of these changes results in the endometrium changing into a structure called the

decidua The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilized egg to support. The decidua is under the influe ...

. In humans, the decidua is shed during

childbirth Childbirth, also known as labour, parturition and delivery, is the completion of pregnancy, where one or more Fetus, fetuses exits the Womb, internal environment of the mother via vaginal delivery or caesarean section and becomes a newborn to ...

. Decidualization plays an important role in promoting placenta formation between a mother and her fetus by mediating the invasiveness of

trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...

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

cell invasion of the endometrium occurs, also known as

hemochorial placentation Placentation is the formation, type and structure, or modes of 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 remo ...

. This allows maternal blood to come into direct contact with the fetal

chorion The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It is also present around the embryo of other animals, like insects and molluscs. Structure In humans and other therian mammals, the cho ...

, 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 Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

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 makes pregnancy possible. The ovarian cycle controls the production and release of eg ...

. 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 The estrous cycle (, originally ) is a set of recurring physiological changes induced by reproductive hormones in females of mammalian subclass Theria. Estrous cycles start after sexual maturity in females and are interrupted by anestrous phase ...

, 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 ma ...

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,

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s, and

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

s. 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 A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's 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 Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, the decidual leukocytes play a role in suppressing the

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

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 Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

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. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

and

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

droplets. Furthermore, they begin secreting cytokines, growth factors, and proteins like

IGFBP1 Insulin-like growth factor-binding protein 1 (IBP-1) also known as placental protein 12 (PP12) is a protein that in humans is encoded by the ''IGFBP1'' gene. Function This gene is a member of the Insulin-like growth factor-binding protein (IGF ...

and

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

, along with

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

(ECM) proteins such as

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...

and

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...

. 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 ...

contacts the endometrial

. 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 (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

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 Ectopic pregnancy is a Complications of pregnancy, complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women ...

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 in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...

, 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, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...

. Chronic deciduitis, a chronic

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

of the decidua, has been linked with

premature birth Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...

In research

The decidualization process is initiated by progesterone, but this requires

cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine tri ...

(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 ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' decidualization results in similar morphological changes to the human ESCs as well as upregulated production of decidualization markers such as

and

. 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 Gynaecological endocrinology Human pregnancy Menstrual cycle