The endometrium is the inner

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 ...

layer, along with its

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...

, of the

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

ian

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

. 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 change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

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 Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...

in humans and some other mammals, including other apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. 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 ...

, the glands and

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

, which supplies

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

and nutrition to the

embryo An embryo ( ) is the initial stage of development for 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 sp ...

and

fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...

.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

Histology of normal simple columnar epithelium of the endometrium

The endometrium consists of a single layer of columnar epithelium 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, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

that varies in thickness according to

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

influences. In the

, 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 women 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 (: salpinx), are paired tubular sex organs in the human female body that stretch from the Ovary, ovaries to the uterus. The fallopian tubes are part of the female reproduct ...

s where a potentially life-threatening ectopic pregnancy may occur nearby. * 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 makes pregnancy possible. The ovarian cycle controls the production and release of eg ...

. Proliferation is induced by

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

(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"; : 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 the ...

(luteal phase). It is adapted to provide an optimum environment for the implantation and growth of the

. This layer is completely shed during

. * 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

. It is possible to identify the phase of the menstrual cycle by reference to either the ovarian cycle or the uterine cycle 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 resi ...

and

thyrotropin-releasing hormone Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone (TSH) as well as prolactin from the anterior pituitary. TRH has been used ...

both expressed in the proliferative phase, and PAEP 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 Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

are also expressed in other types of female tissue types, such as the

cervix The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

and

breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

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

microorganism A microorganism, or microbe, is an organism of microscopic scale, microscopic size, which may exist in its unicellular organism, single-celled form or as a Colony (biology)#Microbial colonies, colony of cells. The possible existence of unseen ...

s 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 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 A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...

. 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 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 ...

''Lactobacillus'' is not the dominant type and there are higher levels of '' Streptococcus'' and ''

Staphylococcus ''Staphylococcus'', from Ancient Greek σταφυλή (''staphulḗ''), meaning "bunch of grapes", and (''kókkos''), meaning "kernel" or " Kermes", is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillale ...

'' species. Half of the cases of bacterial vaginitis showed a polymicrobial

biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...

attached to the endometrium.

Function

The endometrium is the innermost lining layer of the

, and functions to prevent adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the

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 ...

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

, the glands and

s in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the

, which supplies

and nutrition to the

and

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

, whereas most other mammals are subject to an estrous cycle. In both cases, the endometrium initially proliferates under the influence of

. However, once

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 ...

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 ma ...

. 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 In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...

. 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 Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

, 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

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), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...

. 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

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s at different stages of the cycle and this affects other parts of the

reproductive system The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are al ...

Diseases related with endometrium

Endometrial histopathologies and cytopathologies

Chorionic tissue can result in marked endometrial changes, known as an Arias-Stella reaction, that have an appearance similar to

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Historically, this change was diagnosed as

endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...

and it is important only in so far as it should not be misdiagnosed as cancer. * Adenomyosis is the growth of the endometrium into the muscle layer of the uterus (the myometrium). *

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 ...

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 epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...

is the most common

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 Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

) 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

. Treatments that can improve endometrial thickness include

Vitamin E Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...

, L-arginine and sildenafil citrate. Gene expression profiling using cDNA microarray can be used for the diagnosis of endometrial disorders. The

European Menopause and Andropause Society European, or Europeans, may refer to: In general * ''European'', an adjective referring to something of, from, or related to Europe ** Ethnic groups in Europe ** Demographics of Europe ** European cuisine, the cuisines of Europe and other We ...

(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 In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating the ovulatory process, then removing an ovum or ova (egg or eggs) from ...

by an

odds ratio An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of event A taking place in the presence of B, and the odds of A in the absence of B ...

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. The optimal endometrial thickness is 10mm. Nevertheless, in human a perfect synchrony is not necessary; if the endometrium is not ready to receive the embryo an ectopic pregnancy may occur. This consist of the implantation of the blast outside the uterus, which can be extremely dangerous. Triple-line endometrium

Observation of the endometrium by transvaginal ultrasonography is used when administering fertility medication, such as in

. At the time of

embryo transfer Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique - which is often used in connection with in vitro fertili ...

, 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 (usually displayed as light) line in the middle surrounded by two more hypoechoic (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 thickness is also associated with live births in IVF. The live birth rate in a normal endometrium is halved when the thickness is <5mm.

Endometrial protection

Estrogens stimulate endometrial proliferation and

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...

. Conversely, progestogens inhibit endometrial proliferation and carcinogenesis caused by estrogens and stimulate differentiation of the endometrium into decidua, which is termed endometrial transformation 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

caused by estrogens is referred to as ''endometrial protection''. As a result of endometrial protection, endometrial cells can undergo epithelial-mesenchymal transition and be detected in menstrual fluid.

Endometrial receptivity

Endometrial receptivity is a crucial factor in achieving successful embryo implantation in assisted reproduction treatments. It refers to the ability of the endometrium to accept an embryo during a specific time window, known as the "implantation window." The synchronization between endometrial development and the embryo is essential to ensure a successful pregnancy. Currently, there are three main tests that help evaluate endometrial receptivity and optimize fertility treatments: ERA (Endometrial Receptivity Analysis): This genetic test analyzes the expression of specific genes in the endometrium to identify whether it is in a receptive, pre-receptive or post-receptive phase, allowing the ideal moment for embryo transfer to be personalized. EMMA (Endometrial Microbiome Metagenomic Analysis) and ALICE (Analysis of Infectious Chronic Endometritis): Perform a test on the intrauterine microflora, using a small sample of the endometrium, in order to determine the presence of microorganisms that may promote or harm embryo implantation.

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

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...

. 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 Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...

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