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Endometrium
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==Structure== [[File:Histology of normal simple columnar epithelium of the endometrium.jpg|thumb|Histology of the most superficial layer of the endometrium, consisting of a simple columnar epithelium. [[H&E stain]]]] [[File:Endometrium ocp use3.jpg|thumb|right|High magnification [[micrograph]] of [[decidualization|decidualized]] endometrium due to exogenous [[progesterone]] ([[oral contraceptive pill]]). [[H&E stain]]]] [[File:Endometrium ocp use0.jpg|thumb|right|Low magnification micrograph of decidualized endometrium. H&E stain]] The endometrium consists of a single layer of [[columnar epithelium]] plus the [[Stroma (animal tissue)|stroma]] on which it rests. The stroma is a layer of [[connective tissue]] that varies in thickness according to [[hormonal]] influences. In the [[uterus]], simple [[tubular gland]]s reach from the endometrial surface through to the base of the stroma, which also carries a rich blood supply provided by the [[spiral artery|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]]s where a potentially life-threatening [[ectopic pregnancy]] may occur nearby.<ref name=histology/><ref name=Guyton2006/> * 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]]. Proliferation is induced by [[estrogen]] (follicular phase of menstrual cycle), and later changes in this layer are engendered by progesterone from the [[corpus luteum]] (luteal phase). It is adapted to provide an optimum environment for the [[Implantation (embryology)|implantation ]] and growth of the [[embryo]]. This layer is completely shed during [[menstruation]]. * 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,<ref name="Gargett"/> 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]]. It is possible to identify the phase of the menstrual cycle by reference to either the [[Menstrual cycle#Ovarian cycle|ovarian cycle]] or the [[Menstrual cycle#Uterine cycle|uterine cycle]] by observing microscopic differences at each phase—for example in the ovarian cycle: {| class="wikitable" ! Phase !! Days !! Thickness !! Epithelium |- | Menstrual phase || 1–5 || Thin || Absent |- | [[Follicular phase]] || 5–14 || Intermediate || Columnar |- | [[Luteal phase]] || 15–27 || Thick || Columnar. Also visible are [[arcuate vessels of uterus]] |- | [[Ischemic phase]] || 27–28 || || Columnar. Also visible are arcuate vessels of uterus |} ===Gene and protein expression=== {{Further |Bioinformatics#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.<ref>{{Cite web|url=https://www.proteinatlas.org/humanproteome/endometrium|title=The human proteome in endometrium - The Human Protein Atlas|website=www.proteinatlas.org|access-date=2017-09-25}}</ref><ref>{{Cite journal|last1=Uhlén|first1=Mathias|last2=Fagerberg|first2=Linn|last3=Hallström|first3=Björn M.|last4=Lindskog|first4=Cecilia|last5=Oksvold|first5=Per|last6=Mardinoglu|first6=Adil|last7=Sivertsson|first7=Åsa|last8=Kampf|first8=Caroline|last9=Sjöstedt|first9=Evelina|date=2015-01-23|title=Tissue-based map of the human proteome|journal=Science|language=en|volume=347|issue=6220|pages=1260419|doi=10.1126/science.1260419|issn=0036-8075|pmid=25613900|s2cid=802377}}</ref> 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]] and [[thyrotropin-releasing hormone]] both expressed in the proliferative phase, and [[PAEP]] expressed in the secretory phase. Other proteins such as the [[HOXA11|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 alpha|estrogen receptor]] are also expressed in other types of female tissue types, such as the [[cervix]], [[fallopian tube]]s, [[Ovary|ovaries]] and [[breast]].<ref>{{Cite journal|last1=Zieba|first1=Agata|last2=Sjöstedt|first2=Evelina|last3=Olovsson|first3=Matts|last4=Fagerberg|first4=Linn|last5=Hallström|first5=Björn M.|last6=Oskarsson|first6=Linda|last7=Edlund|first7=Karolina|last8=Tolf|first8=Anna|last9=Uhlen|first9=Mathias|date=2015-10-21|title=The Human Endometrium-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling|journal=OMICS: A Journal of Integrative Biology|volume=19|issue=11|pages=659–668|doi=10.1089/omi.2015.0115|pmid=26488136}}</ref> ===Microbiome speculation=== The uterus and endometrium was for a long time thought to be sterile. The [[cervical mucus plug|cervical plug]] of mucosa was seen to prevent the entry of any [[microorganism]]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.<ref name="Baker"/> 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]].<ref name="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]] ''Lactobacillus'' is not the dominant type and there are higher levels of ''[[Streptococcus]]'' and ''[[Staphylococcus]]'' species. Half of the cases of [[bacterial vaginitis]] showed a polymicrobial [[biofilm]] attached to the endometrium.<ref name="Baker"/>
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