The endometrium is the inner
epithelial layer, along with its
mucous membrane, of the
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian
uterus. It has a basal layer and a functional layer: the basal layer contains
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
s which regenerate the functional layer.
The functional layer thickens and then is shed during
menstruation
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
in humans and some other mammals, including
apes,
Old World monkeys, some species of
bat, the
elephant shrew and the
Cairo spiny mouse
The Cairo spiny mouse (''Acomys cahirinus''), also known as the common spiny mouse, Egyptian spiny mouse, or Arabian spiny mouse, is a nocturnal species of rodent in the family Muridae. It is found in Africa north of the Sahara, where its natur ...
. In most other mammals, the endometrium is reabsorbed in the
estrous cycle. During
pregnancy, the glands and
blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the
placenta, which supplies
oxygen and nutrition to the
embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
and
fetus.
[Blue Histology - Female Reproductive System]
. School of Anatomy and Human Biology — The University of Western Australia Accessed 20061228 20:35 The speculated presence of an endometrial microbiota
has been argued against.
Structure

The endometrium consists of a single layer of
columnar epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular ...
plus the
stroma on which it rests. The stroma is a layer of
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
that varies in thickness according to
hormonal influences. In the
uterus, simple
tubular glands reach from the endometrial surface through to the base of the stroma, which also carries a rich blood supply provided by the
spiral arteries. In a woman with a uterus of reproductive age, two layers of endometrium can be distinguished. These two layers occur only in the endometrium lining the cavity of the uterus, and not in the lining of the
Fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s.
[
* The ''functional layer'' is adjacent to the uterine cavity. This layer is built up after the end of menstruation during the first part of the previous ]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 ...
. Proliferation is induced by estrogen (follicular phase of menstrual cycle), and later changes in this layer are engendered by progesterone from the corpus luteum
The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is t ...
(luteal phase). It is adapted to provide an optimum environment for the implantation and growth of the embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. This layer is completely shed during menstruation
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
.
* The ''basal layer'', adjacent to the myometrium and below the functional layer, is not shed at any time during the menstrual cycle. It contains stem cells that regenerate the functional layer, which develops on top of it.
In the absence of progesterone, the arteries supplying blood to the functional layer constrict, so that cells in that layer become ischaemic and die, leading to menstruation
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
.
It is possible to identify the phase of the menstrual cycle by reference to either the ovarian cycle or the uterine 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 ...
by observing microscopic differences at each phase—for example in the ovarian cycle:
Gene and protein expression
About 20,000 protein coding genes are expressed in human cells and some 70% of these genes are expressed in the normal endometrium. Just over 100 of these genes are more specifically expressed in the endometrium with only a handful genes being highly endometrium specific. The corresponding specific proteins are expressed in the glandular and stromal cells of the endometrial mucosa. The expression of many of these proteins vary depending on the menstrual cycle, for example the progesterone receptor
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In humans, PR is encoded by a single ''PGR'' gene resid ...
and thyrotropin-releasing hormone both expressed in the proliferative phase, and PAEP
Glycodelin (GD) also known as human placental protein-14 (PP-14) progestogen-associated endometrial protein (PAEP) or pregnancy-associated endometrial alpha-2 globulin is a glycoprotein that inhibits cell immune function and plays an essential ...
expressed in the secretory phase. Other proteins such as the HOX11 protein that is required for female fertility, is expressed in endometrial stroma cells throughout the menstrual cycle. Certain specific proteins such as the estrogen receptor are also expressed in other types of female tissue types, such as the cervix
The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
, fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...
s, ovaries and breast.
Microbiome speculation
The uterus and endometrium was for a long time thought to be sterile. The cervical plug of mucosa was seen to prevent the entry of any microorganisms ascending from the vagina. In the 1980s this view was challenged when it was shown that uterine infections could arise from weaknesses in the barrier of the cervical plug. Organisms from the vaginal microbiota could enter the uterus during uterine contractions
Uterine contractions are muscle contractions of the uterine smooth muscle that occur during the menstrual cycle and labour. Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation.
Throughout ...
in the menstrual cycle. Further studies sought to identify microbiota specific to the uterus which would be of help in identifying cases of unsuccessful IVF and miscarriages. Their findings were seen to be unreliable due to the possibility of cross-contamination in the sampling procedures used. The well-documented presence of '' Lactobacillus'' species, for example, was easily explained by an increase in the vaginal population being able to seep into the cervical mucous. Another study highlighted the flaws of the earlier studies including cross-contamination. It was also argued that the evidence from studies using germ-free offspring of axenic animals (germ-free) clearly showed the sterility of the uterus. The authors concluded that in light of these findings there was no existence of a microbiome.
The normal dominance of Lactobacilli in the vagina is seen as a marker for vaginal health. However, in the uterus this much lower population is seen as invasive in a closed environment that is highly regulated by female sex hormones, and that could have unwanted consequences. In studies of 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 ...
''Lactobacillus'' is not the dominant type and there are higher levels of '' Streptococcus'' and ''Staphylococcus
''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultative ...
'' species. Half of the cases of bacterial vaginitis
Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination ...
showed a polymicrobial biofilm attached to the endometrium.
Function
The endometrium is the innermost lining layer of the uterus, and functions to prevent adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. 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 ...
or estrous cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer. This represents an optimal environment for the implantation of a 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 ...
upon its arrival in the uterus. The endometrium is central, echogenic (detectable using ultrasound scanners), and has an average thickness of 6.7 mm.
During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
and fetus.
Cycle
The functional layer of the endometrial lining undergoes cyclic regeneration from stem cells in the basal layer. Humans, apes, and some other species display 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 ...
, whereas most other mammals are subject to an estrous cycle. In both cases, the endometrium initially proliferates under the influence of estrogen. However, once ovulation occurs, the ovary (specifically the corpus luteum) will produce much larger amounts 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 ...
. This changes the proliferative pattern of the endometrium to a secretory lining. Eventually, the secretory lining provides a hospitable environment for one or more blastocysts.
Upon fertilization, the egg may implant into the uterine wall and provide feedback to the body with human chorionic gonadotropin (hCG). hCG provides continued feedback throughout pregnancy by maintaining the corpus luteum, which will continue its role of releasing progesterone and estrogen. In case of implantation, the endometrial lining remains as '' decidua''. The decidua becomes part of the placenta; it provides support and protection for the gestation.
Without implantation of a fertilized egg, the endometrial lining is either reabsorbed (estrous cycle) or shed (menstrual cycle). In the latter case, the process of shedding involves the breaking down of the lining, the tearing of small connective blood vessels, and the loss of the tissue and blood that had constituted it through the vagina. The entire process occurs over a period of several days. Menstruation may be accompanied by a series of uterine contractions; these help expel the menstrual endometrium.
If there is inadequate stimulation of the lining, due to lack of hormones, the endometrium remains thin and inactive. In humans, this will result in amenorrhea, or the absence of a menstrual period. After menopause, the lining is often described as being atrophic. In contrast, endometrium that is chronically exposed to estrogens, but not to progesterone, may become hyperplastic. Long-term use of oral contraceptives with highly potent progestin
A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...
s can also induce endometrial atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
.
In humans, the cycle of building and shedding the endometrial lining lasts an average of 28 days. The endometrium develops at different rates in different mammals. Various factors including the seasons, climate, and stress can affect its development. The endometrium itself produces certain hormones at different stages of the cycle and this affects other parts of the reproductive system.
Diseases related with endometrium
Chorionic tissue
Chorionic villi are villi that sprout from the chorion to provide maximal contact area with maternal blood.
They are an essential element in pregnancy from a histomorphologic perspective, and are, by definition, a product of conception. Branche ...
can result in marked endometrial changes, known as an Arias-Stella reaction
Arias-Stella reaction, also Arias-Stella phenomenon, is a benign change in the endometrium associated with the presence of chorionic tissue.
Arias-Stella reaction is due to progesterone primarily. Cytologically, it looks like a malignancy and, his ...
, that have an appearance similar to cancer. Historically, this change was diagnosed as endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
and it is important only in so far as it should not be misdiagnosed as cancer.
* Adenomyosis
Adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus (endometrium) atypically located among the cells of the uterine wall (myometrium), as a result, thickening of the uterus occurs. A ...
is the growth of the endometrium into the muscle layer of the uterus (the myometrium).
* 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 ...
is the growth of tissue similar to the endometrium, outside the uterus.
* Endometrial hyperplasia
* Endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
is the most common cancer of the human female genital tract.
* Asherman's syndrome, also known as intrauterine adhesions, occurs when the basal layer of the endometrium is damaged by instrumentation (e.g., D&C) or infection (e.g., endometrial tuberculosis) resulting in endometrial sclerosis and adhesion formation partially or completely obliterating the uterine cavity.
Thin endometrium may be defined as an endometrial thickness of less than 8 mm. It usually occurs after menopause. Treatments that can improve endometrial thickness include Vitamin E, L-arginine and sildenafil citrate.
Gene expression profiling using cDNA microarray
A DNA microarray (also commonly known as DNA chip or biochip) is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to ...
can be used for the diagnosis of endometrial disorders.
The European Menopause and Andropause Society (EMAS) released Guidelines with detailed information to assess the endometrium.
Embryo transfer
An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate in in vitro fertilization by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.
Observation of the endometrium by transvaginal ultrasonography is used when administering fertility medication
Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
, such as in in vitro fertilization. At the time of embryo transfer, it is favorable to have an endometrium of a thickness of between 7 and 14 mm with a ''triple-line'' configuration, which means that the endometrium contains a hyperechoic
Echogenicity (misspelled sometimes as echogenecity) or echogeneity is the ability to bounce an echo, e.g. return the signal in ultrasound examinations. In other words, echogenicity is higher when the surface bouncing the sound echo reflects increa ...
(usually displayed as light) line in the middle surrounded by two more hypoechoic
Echogenicity (misspelled sometimes as echogenecity) or echogeneity is the ability to bounce an echo, e.g. return the signal in ultrasound examinations. In other words, echogenicity is higher when the surface bouncing the sound echo reflects increa ...
(darker) lines. A ''triple-line'' endometrium reflects the separation of the basal layer and the functional layer, and is also observed in the periovulatory period secondary to rising estradiol levels, and disappears after ovulation.
Endometrial protection
Estrogens stimulate endometrial proliferation
Proliferation may refer to:
Weapons
*Nuclear proliferation, the spread of nuclear weapons, material, and technology
*Chemical weapon proliferation, the spread of chemical weapons, material, and technology
* Small arms proliferation, the spread of ...
and carcinogenesis. Conversely, progestogens inhibit endometrial proliferation and carcinogenesis caused by estrogens and stimulate differentiation of the endometrium into decidua, which is termed endometrial transformation
Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes (the decidual reaction) to endometrial stromal cells (ESCs), ...
or decidualization. This is mediated by the progestogenic and functional antiestrogenic effects of progestogens in this tissue. These effects of progestogens and their protection against endometrial hyperplasia and endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
caused by estrogens is referred to as ''endometrial protection''.
Additional images
Image:Endometrial adenocarcinoma (1).jpg, Endometrioid adenocarcinoma from biopsy. H&E stain.
Image:Endometrium_ocp_use2.jpg, Micrograph of decidualized endometrium due to exogenous 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 ...
. H&E stain.
Image:Endometrium_ocp_use1.jpg, Micrograph of decidualized endometrium due to exogenous progesterone. H&E stain.
Image:Endometrial stromal condensation high mag.jpg, Micrograph showing endometrial stromal condensation, a finding seen in menses.
See also
* CYTL1, also known as cytokine-like like protein 1.
* Endometrial ablation
References
External links
* - "The uterus, uterine tubes and ovary with associated structures."
* - "Female Reproductive System uterus, endometrium"
*
*
Histology at utah.edu. Slide is proliferative phase - click forward to see secretory phase
{{Authority control
Mammal female reproductive system
Pelvis