Adenomyosis, formerly known as intrinsic endometriosis, is an invasion of the endometrium into the myometrium and is a specific type of endometriosis that can coexist with “extrinsic” or pelvic endometriosis. It was first named by Frank and described by Bird et al. in 1972 as “benign infiltration of the endometrium into the myometrium, producing diffuse uterine growth that appears microscopically as hypertrophic hyperplasia of the myometrium surrounded by ectopic, nonmalignant endometrioid glands and interstitium”. In the former, the ectopic endometrium invades the entire muscle wall of the uterus, and the extent and depth of invasion may vary from site to site; in the latter, the ectopic endometrium invades only a portion of the muscle wall, similar to a fibroid, but there is no demarcation between it and the surrounding normal tissue. The disease is most often seen in women aged 30-50 years who have given birth to many children. To date, the exact etiology and pathogenesis of adenomyosis are not clearly understood. It is currently believed that the etiology and pathogenesis of adenomyosis and pelvic endometriosis are not identical. The etiology and pathogenesis of adenomyosis mainly involve basal endometrial glandular invagination, estrogen sulfate esterase activity, immune factors, mucin and growth factors. 1. Basal endometrial invagination Uterine adenomyosis arises from infiltration of the basal endometrium into the “split” myometrium, which can be caused by chronic peristalsis and hyperperistalsis of the uterus. This proliferative difference may be due to the difference in the physiological functions of the two cell layers, the functional layer being the location of the blastocyst implantation and the basal layer being the source of post-menstrual the source of regeneration of the functional layer. During regeneration, epithelial cells of basal lamina origin are in direct contact with the spindle cells of the endothelial mesenchyme, whose cellular ultrastructure contains a microtubular microfilament system and a pseudopod protrusion of the cell pulp, features that are coordinated with the amoeboid contractile expansion movement of the cells, but this morphological alteration is not found in adenomyosis lesions. In in vitro studies, ectopic endometrial cells have the same invasive power as metastatic bladder cancer cell lines, and this invasiveness contributes to the expansion of the basal endometrium into the myometrium. Many authors believe that uterine adenomyosis arises from histocytosis, which is the result of the presence of endometrial mesenchyme formed by multifunctional peripheral cells located in the uterine body and outside the uterus, which induce endothelial epithelial cells. Magnetic resonance and vaginal ultrasound findings suggest that the underlying cause of adenomyosis is an anatomical defect of the myometrium. Both direct endothelial factors and indirect structural/dysfunctional factors of the connecting band caused by an altered immune response may be the starting point in the pathogenesis of adenomyosis. 2. Role of steroid hormones Similar to uterine fibroids, endometriosis, endometrial cancer and breast cancer, adenomyosis has been considered as an estrogen-dependent disease. Clinical studies have confirmed that the course and development of the disease can be delayed by suppressing estrogen levels, therefore, estrogen is closely related to the development of adenomyosis. Clinical studies have found that low estrogen therapy is less effective in treating adenomyosis than endometriosis, and the reason for this may be related to the mutation of estrogen receptors in the adenomyosis tissue. The somatic estrogen receptors in uterine adenomyosis have a gene mutation using PCR/single-stranded conformational polymorphism analysis, and their functional characteristics suggest either severely damaged DNA binding and subsequent transactivation in response to changes in estrogen, or changes in ligand one non-dependent activation mediated by epithelial factors, although the exact mechanism is not known, but mutations related to unresponsiveness to estrogen may lead to ectopic cells in the lesion to low Tolerance and resistance to estrogen therapy. 3. Immune factors A series of immune responses are activated in patients with uterine adenomyosis, including strong expression of cell surface antigens, increased numbers of macrophages or immune cycles, and deposition of immunoglobulin and complement components. The activated immune cells secrete different cytokines or growth factors, which stimulate the expression of cell surface antigens and eventually cause a “defective cycle” of immunity, in an immune emergency and by synthesizing heat shock proteins to protect themselves. In adenomyosis, the expression of the major histocompatibility complex type II antigens is enhanced in both in situ and ectopic endometrium, especially in adenosepithelial cells, and the HLA II antigens of ectopic endometrial cells are recognized by macrophages, which in turn activate T cells and stimulate B cells to produce antibodies. The increased number of macrophages in the in situ and ectopic endometrium not only has an antigen-presenting role, but also may play a role in the reduced fertility due to the disease through the action of cytokines such as interleukin I and TNF.The increased number of T cells in the in situ and ectopic endometrium in adenomyosis is associated with the stimulation of the inflammatory response due to disease-induced hemorrhage/necrosis, and after activation, by secreting a large number of cytokines, which are involved in disease development, and also promote B-cell differentiation and immunoglobulin production, the role of the latter in the immune regulation of adenomyosis being unclear. Humoral immunity is also involved in the pathogenesis of uterine adenomyosis. The closer the endometrial cells are to the active T cells, the more pronounced is the suppression of their growth. Most of the lymphoid follicular structures are located at the endometrial adenomyotic junction rich in active T helper cells and morphologically coincide with the most inhibitory sites of endometrial cells, while the uterus with adenomyosis happens to lack active T cells. Although the current findings confirm the involvement of abnormalities in the immune system in the development of adenomyosis, it is unclear whether this abnormality is an independent pathogenic factor. 4. Angiogenesis Angiogenesis is a necessary condition for the formation of ectopic lesions. Active endometrial angiogenesis was first observed in the functional layer of adenomyosis. Thereafter, the results of computer morphological analysis of endometrial basal layer vessels showed that the number and area of vessels in the proliferative and secretory phases were significantly increased in patients with adenomyosis compared with controls. In a pituitary transplantation rat model of adenomyosis, the area and diameter of endometrial blood vessels increased significantly in adenomyosis rats, and there was also a tendency to increase the area of blood vessels in the myometrium and a significant expansion of blood vessels. These findings suggest that adenomyosis has a vascular proliferation characteristic of the invasive process. Immunohistochemistry was used to detect the expression of VEGF in adenomyosis tissues, and the results showed that the expression of VEGF was higher in the adenomyosis group than in the myometrium group, and increased significantly in the secretory phase, while the intensity of VEGF expression in the mesenchymal cells decreased significantly in the secretory phase; the intensity of VEGF expression in the ectopic endothelial glandular epithelial cells increased significantly compared with the in situ endothelium, but there was no cyclical change. The increase of VEGF expression in glandular epithelium in secretory phase increases the permeability of endometrial interstitial vessels and leads to interstitial edema and fibrin deposition, which induces angiogenesis and creates conditions for endometrial invasion into the myometrium. 5, genetic factors Endometriosis as a polygenic disease has a genetic predisposition, and some genetic polymorphisms have been found in studies. For example, the uterus of recombinant SMXA rats can spontaneously develop histological changes of adenomyosis. In F1 rats similar to recombinant SMXA rats, there are even more prominent adenomyosis alterations similar to those in humans. Therefore, it is believed that genetic factors may be involved in the development of uterine adenomyosis, but the role in the pathogenesis of the disease remains to be confirmed by research. 6. Other factors Local cytokine imbalance similar to endometriosis was also found in adenomyosis. In the supernatants of in vitro cultured mononuclear cells from in situ and ectopic endometrium of patients with adenomyosis, interferon 7, INFa, TNFa, IL-lB and epidermal growth factor were higher in in situ endometrial mononuclear cells than in controls, while IL I 8 was lower than the control group, while INFy, INFa, and TNFa were higher in ectopic endothelium than in the control group. IL-1, IL-8, and EGF produced by ectopic endothelial mononuclear cells were significantly reduced, indicating that impaired local cytokine production has an important role in the development of uterine adenomyosis. Many animal experiments have illustrated that matrix metalloproteinases play a key role in the degradation of extracellular matrix. The ability of endometrial mesenchymal cells to erode into various components of the ECM was observed in in vitro experiments induced by adenomyosis in mice, and the results showed that a large number of mesenchymal cells taken from adenomyotic endometrium eroded more significantly into the stromal gel than those taken from normal endometrium; and the addition of MMP inhibitors to the reaction system significantly reduced the number of mesenchymal cells from adenomyotic endometrium eroding into the stromal gel The number of interstitial cells in adenomyosis endometrium eroding into the stromal gel was significantly reduced after adding MMP inhibitor to the reaction system. The expression of MMP2 and MMP9 in adenomyosis and control uteri was determined by gelatin zymography, and the intensity of their expression increased with the severity of the disease; the overexpression of MMP2 increased the erosive capacity of the endometrium and degraded the extracellular matrix, including the basement membrane, surrounding the ectopic endometrium, providing the conditions for the formation of ectopic lesions in adenomyosis. In any case, it should be acknowledged that many questions remain to be answered regarding the origin and pathogenesis of adenomyosis, and more experimental and anthropologically relevant studies are needed.