The endometrium is the inner lining of the uterus. Its physiological functions are to prepare for the implantation of an embryo, to maintain a pregnancy if implantation occurs and, in women, to be shed as menstruation when it does not. Around it lies the myometrium, the muscular wall of the uterus. The scope of research on the uterus is wide: the archive behind this page ranges from uterine glands and immune cells to the mechanics of labour, and from oestrus detection in antelopes to the origins of endometriosis.
A tissue that rebuilds itself every month
Menstruation is regulated by steroid hormones. After ovulation, progesterone from the corpus luteum converts the oestrogen-primed endometrium into a tissue ready to receive an embryo. If pregnancy does not follow, the fall in progesterone is the trigger for menstruation. The menstruating endometrium is, in effect, a wounded surface that must repair itself rapidly every month, which makes it an accessible human model of inflammation and tissue repair. Regeneration of the lining is thought to involve the recruitment of stem or progenitor cells.
A key process in the second half of the cycle is decidualisation: the transformation of the connective-tissue (stromal) cells of the endometrium into specialised secretory decidual cells, which provide nourishment and an immunologically protected environment for the implanting embryo. In most mammals decidualisation occurs only in response to an embryo. In humans it happens every cycle, driven by the post-ovulatory rise in progesterone, whether or not an embryo is present. When progesterone falls, the decidualised tissue breaks down and is shed. How the hormonal cycle itself is generated is described on the reproductive cycle and corpus luteum page.
Receptivity and the dialogue with the embryo
One influential hypothesis holds that spontaneous decidualisation is an evolutionary adaptation to human embryos, which are unusually invasive and frequently carry chromosomal errors. On this view, decidual cells do not simply accept any embryo: they respond to individual embryos in a way that either supports implantation or promotes early rejection, acting as a form of quality control. Disorders that disturb the programming or progression of decidualisation are thought to predispose to pregnancy failure. The embryo’s side of this dialogue is covered on the embryo development and implantation page.
The endometrium also matters when nothing goes wrong with fertility. Abnormal uterine bleeding, including heavy menstrual bleeding, affects one in four women of reproductive age. Drugs that modulate the progesterone receptor can reduce bleeding, but how they do so remains largely unknown, and reviewers note that many basic questions about menstruation are still unanswered, partly because the subject has long been taboo.
Endometriosis: what it is
Endometriosis is a condition in which tissue similar to the lining of the uterus grows outside it, typically on the lining of the pelvis and on the ovaries. The World Health Organization estimates that it affects roughly 10% of women of reproductive age worldwide, about 190 million people. Symptoms listed by WHO include severe period pain, heavy menstrual bleeding, chronic pelvic pain, bloating, nausea and infertility; NICE adds deep pain during or after sex and period-related bowel or urinary symptoms. WHO notes that diagnosis is often delayed by years and that there is currently no cure; treatment aims to control symptoms. Among women with infertility, an estimated 25–50% have endometriosis.
Approaches to diagnosis have changed. Diagnosis traditionally relied on surgery (laparoscopy) to see the lesions, but WHO now notes that imaging such as ultrasound or MRI can be used and that surgery is not always needed first. The 2022 guideline of the European Society of Human Reproduction and Embryology (ESHRE) introduced major changes to recommendations on the role of diagnostic laparoscopy and added a section on adolescents. In England, NICE guidance updated in 2024 recommends offering a transvaginal ultrasound scan to anyone with suspected endometriosis, stresses that a normal scan does not rule the condition out, and advises against using the blood marker CA125 for diagnosis; laparoscopy is still considered when imaging is normal.
Why does it happen? Competing theories
The cause of endometriosis is unknown, and no single theory explains every form of the disease. The main proposals are:
- Retrograde menstruation. Proposed by Sampson in 1927, this theory holds that fragments of endometrium flow backwards through the fallopian tubes during menstruation and implant on pelvic surfaces. It is the most widely accepted explanation, but backward flow is documented in most women with open tubes, so additional factors must decide who develops disease.
- Coelomic metaplasia and embryonic remnants. Cells lining the abdominal cavity, or cells left behind during development of the reproductive tract, may transform into endometrium-like tissue. Interest in such ideas persists because transplantation theories cannot account for rare cases in men, in girls before their first period or in women born without a functional uterus, although each alternative has weaknesses of its own.
- Stem cells and spread through blood or lymph. Endometrial or bone-marrow-derived stem cells, or spread through vessels, may account for lesions far from the pelvis.
Whatever their origin, lesions show characteristic features: they produce their own oestrogen, respond poorly to progesterone, and persist in a peritoneal environment where immune clearance appears impaired. Whether these immune changes are a cause or a consequence of the disease is unresolved. WHO notes that people with endometriosis have higher rates of some autoimmune and inflammatory conditions. Genetics also plays a part: twin studies suggest a heritability of around 50%, yet the genetic variants identified so far explain only a small share of the risk.
Established and still debated
It is established that menstruation is triggered by progesterone withdrawal, that the human endometrium decidualises spontaneously each cycle, and that endometriosis is a common, oestrogen-dependent inflammatory condition with a substantial impact on pain and fertility. Still debated are the relative importance of the competing theories of origin, the role of the immune system, the best non-surgical route to diagnosis, and why only some people exposed to retrograde menstruation develop disease.
Sources
- Critchley HOD et al., Physiological Reviews, 2020 — Physiology of the endometrium and regulation of menstruation (doi:10.1152/physrev.00031.2019)
- Gellersen B, Brosens JJ, Endocrine Reviews, 2014 — Cyclic decidualization of the human endometrium in reproductive health and failure (doi:10.1210/er.2014-1045)
- WHO, “Endometriosis” fact sheet
- NICE guideline NG73, Endometriosis: diagnosis and management (last updated 2024) — Recommendations
- ESHRE, Endometriosis guideline, 2022
- Laganà AS et al., International Journal of Molecular Sciences, 2019 — The pathogenesis of endometriosis: molecular and cell biology insights (doi:10.3390/ijms20225615)
References from the journal archive
These articles were published in Reproduction, the Journal of Reproduction and Fertility or Reviews of Reproduction and are still cited at their old addresses on this domain. Each link leads to the publisher’s version through its DOI.
- EFFECT OF 6-(1′-METHYL-4′-NITRO-5′-IMIDAZOLYL)-MERCAPTOPURINE AND 2-AMINO-6-(1′-METHYL-4′-NITRO-5′-IMIDAZOLYL)-MERCAPTOPURINE ON THE RAT LITTER IN UTERO
- THE EIGHTH OLIVER BIRD LECTURE INTRA-UTERINE CONTRACEPTIVE DEVICES
- ACTION OF OESTROGEN ON THE BLASTOCYST AND UTERUS IN DELAYED IMPLANTATION— AN AUTORADIOGRAPHIC STUDY
- MEASUREMENT OF INTRA-VAGINAL AND INTRA-UTERINE PRESSURES DURING HUMAN COITUS BY RADIO-TELEMETRY
- STIMULATION OF RNA SYNTHESIS IN THE BLASTOCYST AND UTERUS OF THE RAT BY ADENOSINE 3′5′-MONOPHOSPHATE (CYCLIC ApMP)
- THE EFFECT OF DOSE LEVEL OF INTRAVAGINAL PROGESTAGEN ON SPERM TRANSPORT, FERTILIZATION AND LAMBING IN THE CYCLIC MERINO EWE
- USE OF A SPOT TEST FOR CHLORIDE IN CERVICAL MUCUS FOR SELF-DETECTION OF THE FERTILE PHASE IN WOMEN
- CONTINUOUS MEASUREMENT BY RADIO-TELEMETRY OF VAGINAL pH DURING HUMAN COITUS
- ENDOMETRIAL DIFFERENTIATION IN THE PREGNANT SOW AND THE NECROTIC TIPS OF THE ALLANTOCHORION
- THE EFFECT OF A COPPER-RELEASING INTRAUTERINE DEVICE ON SPERM PENETRATION IN HUMAN CERVICAL MUCUS IN VITRO
- THE EFFECT OF CIS - AND TRANS -CLOMIPHENE CITRATE ON SIALIC ACID IN THE UTERUS, CERVIX AND VAGINA OF RATS DURING DELAYED IMPLANTATION
- AUTORADIOGRAPHIC STUDIES ON [3H]OESTRADIOL LOCALIZATION IN THE BLASTOCYSTS AND UTERUS OF RATS DURING DELAYED IMPLANTATION
- MACROMOLECULAR COMPONENTS OF THE LUMINAL FLUID FROM THE BOVINE UTERUS
- CYCLIC CHANGES IN THE METABOLISM OF GLYCOGEN IN CERVICAL MUCUS OF BONNET MONKEYS ( MACACA RADIATA )
- The effect of indomethacin on uterine contractility and luteal regression in pregnant rats at term
- Fertilization and development capability of bovine follicular oocytes matured in vitro and in vivo and transferred to the oviducts of rabbits and cows
- Histological changes in the cervix of the rabbit after coitus
- The movement of human spermatozoa in cervical mucus
- The estimation of sperm motility in semen, on a membrane slide, by measuring the area change frequency with an image analysing computer
- The movement of amino acids into rabbit oviductal fluid
- Concurrent uterine venous and ovarian arterial prostaglandin F concentrations in heifers treated with oxytocin
- Electrolytes in vaginal fluid during the menstrual cycle of coitally active and inactive women
- Investigation of sperm-induced cervical leucocytosis by a double mating study in rabbits
- Maintenance of the corpus luteum after uterine transfer of trophoblastic vesicles to cyclic cows and ewes
- Xenogenous fertilization of goat ova in the rabbit oviduct
- Inequality in function of the right and left ovaries and uterine horns of the mouse
- Stimulation of early embryonic development in the sheep by co-culture with oviduct epithelial cells
- Hormonal and behavioural detection of oestrus in blackbuck, Antilope cervicapra , and successful artificial insemination with fresh and frozen semen
- The formation and function of oviduct fluid
- Changes in phospholipids, cholesterol and protein content of oviduct fluid of cows during the oestrous cycle
- 1,25-Dihydroxyvitamin D3 induces in vivo the decidualization of rat endometrial cells
- Infiltration of neutrophil polymorphonuclear leucocytes into the endometrial stroma at the time of implantation of ova and the initiation of the oil decidual cell reaction in mice
- Stimulation of 2′,5′-oligoadenylate synthetase activity in sheep endometrium during pregnancy, by intrauterine infusion of ovine trophoblast protein-1, and by intramuscular administration of recombinant bovine interferon-αI1
- Uterine oxytocin receptors in cyclic and pregnant cows
- Expression of colony-stimulating factors and inflammatory cytokines in the uterus of CD1 mice during Days 1 to 3 of pregnancy
- Observations on the turkey oviductal sperm-storage tubule using differential interference contrast microscopy
- Concentrations of progesterone and oxytocin receptors in endometrium of postpartum cows expected to have a short or normal oestrous cycle
- Effects of induction of low plasma progesterone concentrations with a progesterone-releasing intravaginal device on follicular turnover and fertility in cattle
- Leucocyte distribution in the uterus during the preimplantation period of pregnancy and phagocyte recruitment to sites of blastocyst attachment in mice
- Multiple site electromyography recordings of uterine activity following an intrauterine bacterial challenge in mares susceptible and resistant to chronic uterine infection
- Secretion of matrix metalloproteinases by human endometrial cells in vitro
- Leukaemia inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time
- Oestradiol concentration and the development of the uterine oxytocin receptor and oxytocin-induced PGF2α release in ewes
- The direct influence of the embryo on uterine PGF2α and PGE2 production in sheep
- Effects of oestradiol and tamoxifen on oxytocin-induced phospholipase C activation in human myometrial cells
- Morphology of pig uterine subepithelial capillaries after topical and systemic oestrogen treatment
- Role of high molecular weight seminal vesicle proteins in eliciting the uterine inflammatory response to semen in mice
- Effects of supplementation with fetal calf serum on development of bovine embryos in synthetic oviduct fluid medium
- Matrilysin activity in the rat uterus during the oestrous cycle and implantation
- Effect of inhibition of matrix metalloproteinases on endometrial decidualization and implantation in mated rats
- Control of the immunological environment of the uterus
- Effect of nitric oxide synthase inhibitors on ovum transport and oviductal smooth muscle activity in the rat oviduct
- Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour
- Uterine lymphocyte distribution and interleukin expression during early pregnancy in cows
- Expression of oxytocin, oestrogen and progesterone receptors in uterine biopsy samples throughout the oestrous cycle and early pregnancy in cows
- Formation of Fallopian tubal fluid: role of a neglected epithelium
- Human endometrial angiogenesis
- Impact of manipulations of myogenesis in utero on the performance of adult skeletal muscle
- Selective sperm binding to pig oviductal epithelium in vitro
- Temporal changes in reproductive hormones and conceptus-endometrial interactions during embryonic diapause and reactivation of the blastocyst in European roe deer (Capreolus capreolus)
- Use of computer-assisted sperm motility assessment and multivariate pattern analysis to characterize ejaculate quality in Mohor gazelles (Gazella dama mhorr): effects of body weight, electroejaculation technique and short-term semen storage
- Comparison of uteroplacental glycosylation in the camel (Camelus dromedarius) and alpaca (Lama pacos)
- Influence of maternal size on placental, fetal and postnatal growth in the horse. I. Development in utero
- Influence of uterine bacterial contamination after parturition on ovarian dominant follicle selection and follicle growth and function in cattle
- Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis
- Progesterone stimulation of fluid absorption by the rat uterine gland
- Consequences of transvaginal follicular puncture on well-being in cows
- Expression and presence of osteopontin and integrins in the bovine oviduct during the oestrous cycle
- Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling
- Endocrine mechanisms of intrauterine programming
- Endometriosis and the neoplastic process
- Evaluation of antimicrobial peptide nisin as a safe vaginal contraceptive agent in rabbits: in vitro and in vivo studies
- Interferon-τ upregulates prolactin receptor mRNA in the ovine endometrium during the peri-implantation period
- Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig
- Galectin-15 in ovine uteroplacental tissues
- Hydrogen peroxide and superoxide anion modulate pregnant human myometrial contractility
- Leukaemia inhibitory factor in implantation and uterine biology
- 15-Hydroxyprostaglandin dehydrogenase in the bovine endometrium during the oestrous cycle and early pregnancy
- Binding of boar spermatozoa to oviductal epithelium in vitro in relation to sperm morphology and storage time
- Evidence for heterodimeric association of leukemia inhibitory factor (LIF) receptor and gp130 in the mouse uterus for LIF signaling during blastocyst implantation
- Gene and protein expression in the myometrium in pregnancy and labor
- Modulation of peroxisome proliferator-activated receptor δ and γ transcripts in swine endometrial tissue during early gestation
- TGF-β superfamily expression and actions in the endometrium and placenta
- The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in endometrial epithelial cell lines
- Bovine herpesvirus 4 is tropic for bovine endometrial cells and modulates endocrine function
- Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus
- Immunoendocrine aspects of endometrial function and implantation
- Oestrogen and progesterone receptors in the marmoset endometrium: changes during the ovulatory cycle, early pregnancy and after inhibition of vascular endothelial growth factor, GnRH or ovariectomy
- Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium
- Quantitative analysis of changes in endometrial gland morphology during the bovine oestrous cycle and their association with progesterone levels
- Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli
- Spermatozoa stimulate prostaglandin synthesis and secretion in bovine oviductal epithelial cells
- The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells
- The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women
- Bacterial infection of endometrial stromal cells influences bovine herpesvirus 4 immediate early gene activation: a new insight into bacterial and viral interaction for uterine disease
- Characterization of clonogenic stromal cells isolated from human endometrium
- Determination of glycosidase activity in porcine oviductal fluid at the different phases of the estrous cycle
- Dynamic changes in messenger RNA profiles of bovine endometrium during the oestrous cycle
- Expression and regulation of fucosyltransferase 4 in human endometrium
- Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches
- Murine SPAM1 is secreted by the estrous uterus and oviduct in a form that can bind to sperm during capacitation: acquisition enhances hyaluronic acid-binding ability and cumulus dispersal efficiency
- Negative energy balance in dairy cows is associated with specific changes in IGF-binding protein expression in the oviduct
- Ovary and uterus transplantation
- Enhanced focal adhesion assembly reflects increased mechanosensation and mechanotransduction at maternal–conceptus interface and uterine wall during ovine pregnancy
- Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization
- Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus
- Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium?
- RHO protein regulation of contraction in the human uterus
- Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system
- The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse
- The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm–oviduct interaction
- The uterine environment modulates trophectodermal POU5F1 levels in equine blastocysts
- Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility
- Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology
- Pregnancy-related changes in connections from the cervix to forebrain and hypothalamus in mice
- Retrograde tracing of spinal cord connections to the cervix with pregnancy in mice
- Role of the transcriptional factors FOXO1 and PPARG on gene expression of SLC2A4 in endometrial tissue from women with polycystic ovary syndrome
- The effect of elevated progesterone and pregnancy status on mRNA expression and localisation of progesterone and oestrogen receptors in the bovine uterus
- Transient estrogen exposure from birth affects uterine expression of developmental markers in neonatal gilts with lasting consequences in pregnant adults
- Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus
- Comparison of mRNA for IGFs and their binding proteins in the oviduct during the peri-oestrous period between dairy heifers and lactating cows
- Microarray assessment of the influence of the conceptus on gene expression in the mouse uterus during decidualization
- Pregnancy and interferon τ regulate DDX58 and PLSCR1 in the ovine uterus during the peri-implantation period
- Analysis of uterine gene expression in interleukin-15 knockout mice reveals uterine natural killer cells do not play a major role in decidualization and associated angiogenesis
- Cervical remodeling in term and preterm birth: insights from an animal model
- Endometrial inflammation and effect on implantation improvement and pregnancy outcome
- Expression of mesenchymal-related genes by the bovine trophectoderm following conceptus attachment to the endometrial epithelium
- Aberrant expression and regulation of NR2F2 and CTNNB1 in uterine fibroids
- Alkaline phosphatases contribute to uterine receptivity, implantation, decidualization, and defense against bacterial endotoxin in hamsters
- Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?
- Proteomic analysis of human cervicovaginal fluid collected before preterm premature rupture of the fetal membranes
- Stress responses at the endometrial–placental interface regulate labyrinthine placental differentiation from trophoblast stem cells
- Summer heat stress affects prostaglandin synthesis in the bovine oviduct
- Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium
- Common fibroid-associated genes are differentially expressed in phenotypically dissimilar cell populations isolated from within human fibroids and myometrium
- Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment
- Hepatoma-derived growth factor: from the bovine uterus to the in vitro embryo culture
- Seminal plasma aids the survival and cervical transit of epididymal ram spermatozoa
- Alteration in the intrafollicular thiol–redox system in infertile women with endometriosis
- Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action
- Soy isoflavones improves endometrial barrier through tight junction gene expression
- Evidence for a PGF2α auto-amplification system in the endometrium in mares
- In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus
- Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions
- Mechanotransduction mechanisms for coordinating uterine contractions in human labor
- SKAP, an outer kinetochore protein, is required for mouse germ cell development
- A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage
- Bovine embryo-oviduct interaction in vitro reveals an early cross talk mediated by BMP signaling
- Embryo culture in presence of oviductal fluid induces DNA methylation changes in bovine blastocysts
- High-throughput mRNA sequencing of stromal cells from endometriomas and endometrium
- Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse
- Maternal metabolic stress may affect oviduct gatekeeper function
- Modelling aspects of oviduct fluid formation in vitro
- Estrogen is an important mediator of mast cell activation in ovarian endometriomas
- Identification by proteomics of oviductal sperm-interacting proteins