The most common immune cells in peritoneal cavity are MՓs [36]. Peritoneal MՓs (PMՓs) are divided into resident MՓs and monocyte-derived MՓs. The formers are representative of MՓs: they represent a strong phagocytic capacity, displaying longevity and self-renewal ability. Activated MՓs can not only remove damaged tissue, cellular debris and red blood cells via phagocytosis, but also regulate the peritoneal microenvironment with the help of their secreted cytokines, prostaglandins, enzymes and complement components [10]. In turn, those mediators secreted by MՓs promote themselves to induce inflammatory responses, tissue remodel, angiogenesis, and possibly recruitment of endothelial cells [37, 38]. Due to their phenotypic plasticity, activated MՓs can be divided into two types with different functions according to the altered microenvironments [39]. M1 type performs pro-inflammatory functions by secreting numerous inflammatory cytokines to specifically eliminate microorganisms and defective cells. M2 type plays the opposite role by secreting anti-inflammatory factor, participating in regulating adaptive immune responses, facilitating angiogenesis, tissue repair and the removal cell debris [40, 41, 42, 43].

Normally, the M1/M2 MՓs are in balance to keep the body in homeostasis. This balance is skewed in favor of M1 type in the eutopic endometrium in women with endometriosis [44], whereas it tends to be M2 type polarized in the peritoneum and ectopic lesions [45]. Some scholars have proposed that the resident M$\mathrm{\Phi }$s in the ectopic lesions are M1 type, while the monocytes recruited from the peritoneum are M2 type [46]. Although M2 type has long been considered to be dominant in endometriotic lesions, few studies have considered the complexity of MՓs phenotype in response to the local tissue microenvironment, where pro-inflammatory and anti-inflammatory factors may co-exist [47]. Recently, another in vitro study confirmed that the decrease of M1 type migration rate of peritoneal macrophages led to the retention of M1 type macrophages in the peritoneal cavity, which caused the continuation of inflammatory response and promoted the development of endometriosis, and it was considered that inducing macrophage differentiation into M2 type might be a method for the treatment of endometriosis [48]. These findings further complicate the role of MՓs in the development of endometriosis.

Despite the number of activated PMՓs increasing significantly in women with endometriosis [10], their phagocytic capacity is considerably decreased, so that endometrial cells arriving in the pelvic cavity via retrograde menstruation cannot be cleared. Wu et al. [49] found that the content and activity of matrix metalloproteinases (MMPs) expressed by PMՓs in patients with endometriosis were inhibited, through which MՓs bind to extracellular matrix and play a phagocytic role. The downregulation of MMPs may be mediated by the overexpression of prostaglandin E2 (PEG2) in the peritoneal fluid. Other studies have found an increased proportion of free MՓs in the peritoneal cavity of women with endometriosis [50], suggesting that the decrease of conjugated MՓs implies a decrease in phagocytosis, thus sparing ectopic endometrial cells from phagocytosis and allowing them to plant and develop in the peritoneum. In conclusion, PMՓs may (1) regulate the dynamic changes of secreted proinflammatory factors and anti-inflammatory factors through the change of active phenotype; (2) reduce phagocytosis of the endometrium and stroma contained in reflex menstruation to promote the occurrence and development of peritoneal endometriosis.

NK cells, named for their cytotoxic properties, recognize and kill target cells, such as certain tumor cells, virus-infected cells, self-tissue cells (damaged cells), and parasites. They can also synthesize and secrete cytokines to play immune regulation. The regulation of NK cell activity depends on the interaction of two types of receptors expressed on the cell surface, namely activated receptor (KAR) and inhibitory receptor (KIR). KIR protects autologous cells by recognizing MHC-I molecules on their surface to generate inhibitory signals and block the activation of KAR. When the target cells lose MHC-I molecules, the inhibitory effect is relieved and KAR receptor activates NK cells to produce killing effect. KAR receptors, which mainly contain natural killer group 2 member D (NKG2D) and CD16, can bind to target cells coated with immunoglobulin G (IgG) and destroy target cells through an antibody-dependent cell-mediated cytotoxic mechanism. Thus, the increase of NKG2D ligand can trigger cytotoxic reactions of activated NK cells.

Oosterlynck et al. [51] first found reduced cytotoxicity of NK cells in both peritoneal cavity and peripheral blood of patients with endometriosis, confirmed by subsequent studies [52]. González-Foruria et al. [53] found that soluble NKG2D ligands were significantly increased in the peritoneal fluid of patients with endometriosis, implying that fewer NKG2D ligands were expressed on the surface of ectopic endometrial cells. This would make it easier for NK cells to evade recognition due to these soluble NKG2D ligands acting as bait receptors. Wu et al. [54] have found that the excessive expression of KIR in peritoneal NK cells of patients with endometriosis may also explain the decreased activity of NK cells. A recent study found that the chemotaxis (i.e., the ability to migrate to the site of immune response) of peritoneal NK cells decreases in patients with endometriosis, which may lead to the defect of NK cells’ cytotoxic function [55]. It is not clear whether this phenomenon is caused by differences in NK cell function per se or by differences in the peritoneal environment caused by retrograde menstruation, which warrants further exploration. Decreased cytotoxicity and chemotaxis of NK-cells in the peritoneal cavity reduce their ability to clear endometriotic cells and may be associated with the evolution of endometriosis.

Like MՓs, MCs usually reside in the mucosal epithelium of the lungs, digestive tract, and reproductive tract, representing the first line of defense: in humans, they are also positioned at mesothelium-covered cavities including the peritoneal cavity [56]. MCs are degranulated when stimulated by allergens to produce histamine and protease to participate in immunity [57]. MCs can be divided into at least two populations depending on the protease they contain. MCs containing only tryptase are called mucosal mast cells (MMCs) in mice and MC${}_{\text{T}}$ in humans, while MCs containing tryptase, chymase, carboxypeptidase A, and cathepsin G are called connective tissue mast cells (CTMCs) in mice and MC${}_{\text{TC}}$ in humans. The latter are thought to be innate MCs, a unique source of heparin, while the former is smaller, often containing fewer granules, and are thought to be adaptive MCs [58]. Their functional differences mainly depend on the response to different stimuli. Peritoneal MCs are the mature MC${}_{\text{TC}}$ subgroup. Tryptase is a specific marker of mature mast cells [59]. Previous studies have suggested that MCs may be associated with the progression of endometriosis, but they are limited to certain phenomena, such as the increased number of degranulated MCs in endometriotic lesions and the significantly increased tryptase level in the peritoneal fluid of patients with endometriosis [60, 61]. A recent animal study found that estrogen can significantly increase the MCs’ density in endometrial lesions, suggesting that ectopic lesions provide a necessary microenvironment for MCs recruitment and differentiation, while MCs may promote the disease by releasing proinflammatory factors [62]. Tryptase may affect sperm motility and cause low fertility rate of endometriosis, but the results have not been supported [60].

The main function of eosinophils is to regulate allergic reactions and to activate and attack pathogens during parasitic infections. Early studies found an indirect association between eosinophils and endometriosis. Hornung et al. [63] found that in both eutopic endometrium and ectopic endometrium in women with endometriosis, the expression of extaxin, a highly specific eosinophil chemotactic factor, is significantly elevated versus that in normal controls. Blumenthal et al. [64] found that the level of Eosinophil peroxidase (EPO), an enzyme released by degranulated eosinophils, was increased in ectopic lesions of patients with endometriosis. By establishing a mouse model of endometriosis, Uchiide et al. [65] found that the adherent peritoneal stroma showed the proliferation and infiltration of eosinophils related, which was thought to be the peritoneal manifestation in the early stage of endometriosis. A subsequent study found elevated eosinophil counts in the peritoneal fluid of patients with early endometriosis [66]. These studies suggest that eosinophils may be involved in the pathogenesis of endometriosis.

Neutrophils play a crucial role in the innate immune system as the second line of defense against microbial invasion, with strong chemotaxis and phagocytosis. The structure and metabolism of peripheral blood neutrophils in patients with endometriosis are changed [67], and the phagocytic function is decreased [68]. After surgical resection of endometriotic lesions, the phagocytic activity of peripheral blood neutrophils can be restored to normal temporarily, but only for a short time [68]. Conversely, the number of neutrophils is increased both in the peritoneal fluid and ectopic lesions of women with endometriosis, potentially secreting cytokines that promote angiogenesis [69, 70]. Co-culture with peritoneal fluid from patients with endometriosis induces neutrophils to release more vascular endothelial growth factor (VEGF), a factor that increases vascular permeability and promotes angiogenesis [71]. A recent study showed that granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) regulate neutrophils through signal transducer and activator of transcription 3 (STAT3) pathway, altering the expression of angiogenesis-related genes, such as Mmp9, Bombina variegata 8 kDa protein (Bv8), and tumor necrosis factor-related apoptosis-inducing ligand (Trail) to promote the establishment of early endometriosis [72].

DCs, the most powerful specialized antigen-presenting cells discovered, can recognize and phagocytose antigens and present them to T lymphocytes. Generally, DCs are divided into two main groups: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). cDCs contain two subpopulations, namely cDC1 and cDC2, which can recognize and phagocyte antigens before maturing. After differentiation and maturation stimulated by inflammatory factors, mature DCs acquire the ability of migration, antigen presentation and T-cell differentiation. For example, cDC1 subgroup is also commonly referred to as Th1-inducing cells [73]. DCs control the differentiation of Th cells or regulatory T (Treg) cells; accordingly, researchers speculate that DCs could cause their functional abnormalities. Several studies have indicated that abnormal DC frequency in the uterus or peritoneal fluid may lead to endometriosis [74, 75, 76]. Unlike cDCs, pDCs detect the nucleic acid of pathogens and produce an abundance of interferons (IFNs), currently considered as a therapeutic target in endometriosis. According to Suen et al. [77], in the mouse model, IL-10 in endometriosis is mainly derived from pDC secretion; pDC was found to increase endometrial lesions, but this phenomenon was not observed in IL-10 knockout mice [78]. However, other researchers found that the frequency of pDCS in the peritoneal fluid of patients with endometriosis did not change [75]. Further studies on the function of peritoneal pDCs are needed to confirm whether they are associated with the establishment and evolution of endometriosis.

The complement system, a part of the innate immune system, consists of a series of proteins that undergo complex cascades upon activation and are highly effective in labeling the non-self (such as pathogens), altered self (such as apoptotic/necrotic cells and protein complex), and transformed self (such as tumor cells) [79, 80]. This is followed by lysis of target cells/pathogens, opsonization and subsequent enhancement of their uptake by immune phagocytes via complement receptors, and production of inflammatory mediators. Two anaphylatoxins, C3a and C5a, produced by activated complement, act as activators to stimulate peritoneal MCs and macrophages to produce mediators or cytokines; furthermore, increased endometrial vascular permeability causes inflammation and pain symptoms [81]. Numerous studies have found that the levels of various components of complement, such as C1q, C3a, C3c, C4, and sC5b-9 are significantly increased in the peritoneal fluid of patients with endometriosis. Accordingly, the complement system may also be a vital part of the pathogenesis of endometriosis [82, 83, 84].

Adaptive immunity refers to the process of activation, proliferation and differentiation of antigen-specific T/B lymphocytes into effector cells and the production of biological effects after being stimulated by antigens in vivo. According to the different cell types and mechanisms involved in immune response, adaptive immunity can be divided into T-cell-mediated cellular immunity and B-cell-mediated humoral immunity. T lymphocytes, derived from bone marrow and embryonic liver, migrate to thymus and mature into immunocompetent T lymphocytes. According to the differences in their expressed glycoproteins CD4 and CD8, which can bind to MHC-II and MHC-I molecules, respectively, T cells are divided into two major categories [85, 86], namely, CD4${}^{+}$ T cells and CD8${}^{+}$ T cells. CD4${}^{+}$ T cells can be divided into four subsets according to their cytokine secretion profile: Th1, Th17, Th2 and Treg cells. Th1/Th17 cells are classified as pro-inflammatory cells, whereas Th2/Treg cells have anti-inflammatory effects [87]. Th1 cells synthesize pro-inflammatory cytokines such as IFN-$\gamma$, tumor necrosis factor (TNF)-$\alpha$, TNF-$\beta$, IL-2, IL-3, IL-10 and IL-12; they are able to promote CD8${}^{+}$ T cell differentiation and cellular immunity via activation of monocytes and MՓs. Th17 cells produce IL-6/IL-17. Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13, and can promote the differentiation of B cells into plasma cells to promote humoral immune response [17]. Treg cells account for a small proportion of T lymphocytes, only 5–20% of CD4${}^{+}$ cells; they secret IL-10/transforming growth factor (TGF)-$\beta$ and are able to inhibit effector cell responses, limit inflammatory responses, thereby preventing tissue damage and autoimmunity [88, 89]. These four subsets of CD4${}^{+}$ T cells maintain dynamic balance through mutual influence and restriction of cytokines, among which Th1/Th2 and Treg/Th17 are two pairs of balance systems that restrict each other and play an important role in maintaining the immune stability of the body. Disruption of this balance leads to certain diseases including endometriosis.

The concentration of Th2-type cytokines in peripheral blood and peritoneal fluid was found to be elevated in women with endometriosis [90, 91]. Studies have found that compared with normal endometrium, Th17 cells are more commonly present in endometriotic lesions [92], and their content in peritoneal fluid is positively correlated with disease grade [93]. IL-17A secreted by Th17 can stimulate inflammatory response and promote the occurrence of endometriosis [94, 95]. Authors almost unanimously agree that increased Treg cells in the peritoneal fluid are associated with local immune suppression, allowing ectopic endometrial cells to escape clearance [96, 97]. CD8${}^{+}$ T cells have the function of activating macrophages, enabling them to phagocyte cells infected by viruses or intracellular pathogens [85, 86]. It was found that the levels of all subset of T lymphocytes in the peritoneal fluid of women with endometriosis were elevated; a higher ratio of CD4/CD8 was also discovered [98]. There are few independent studies on CD8${}^{+}$ T cells in endometriosis.

B lymphocytes are derived from bone marrow and are released into peripheral lymphoid tissues after they develop into mature B cells, which are activated into plasma cells and begin to secrete antibodies, participating in humoral immunity [99, 100]. Excessive polyclonal activation of B cells has been found in patients with endometriosis via secretion of autoantibodies in endometriotic lesions, peritoneal fluid and blood [101, 102, 103]. Badawy et al. [104] found that the number of B cells was elevated in both the peripheral blood and peritoneal fluid of patients with endometriosis. Another study found that B1 lymphocytes (a subset of B lymphocytes, which do not have memory function but can produce antibodies to attack antigens) in the peritoneal fluid of patients with endometriosis and positive antinuclear antibodies (ANAs) are significantly increased, suggesting that this phenomenon may pertain to endometriosis-related infertility [105]. Others also found that the increase in the number of B cells in the follicular fluid of patients with endometriosis may damage the quality of eggs and cause infertility [106].

Levels of anti-endometrial antibodies and anti-ovarian antibodies have been found to be significantly increased in patients with endometriosis, and elevated levels of IgA and IgG-type antibodies in peritoneal fluid also have been discovered [107, 108]. In addition to anti-tissue and anti-organ antibodies, B lymphocytes also produce antibodies to cellular components, such as antiphospholipid, anti-DNA and ANA, which are commonly seen in autoimmune diseases [9]. An immunoregulatory B cell subtype, called B-reg cells, secretes IL-10, which not only controls effector immune responses, but even controls the progression of autoimmune diseases [97]. Animal experiments [98] suggest that B-reg cells may help prevent the progression of endometrial lesions. An immunoregulatory B-cell subtype, known as B reg cells, controls the progression of autoimmune diseases by secreting IL-10 and TGF-$\beta$, inhibiting the expansion of pro-inflammatory lymphocytes [109]. An animal drug experiment [110] found that promoting the conversion of activated B cells into B-reg cells prevented the progression of endometriosis, suggesting that B-reg cells play a negative role in the progression of endometriotic lesions. In addition to antibodies, activated B cells can also secrete certain cytokines that regulate immune cells and maintain chronic inflammation, which may be related to endometriosis [111, 112, 113, 114].

In conclusion, B cells may participate in the pathogenesis of endometriosis through their own activation and the production of antibodies and a small number of cytokines. However, their role in the microenvironment of endometriosis and their interaction with other immune cells need to be further explored.

IL-1 family are pro-inflammatory and secreted into the peritoneal fluid by activated macrophages [120]. They regulate immune and inflammatory responses by controlling the expression of integrins in leukocytes and endothelial cells [33]; they further mediate the maturity and differentiation of various cells, participating in angiogenesis together with other substances [120]. In this family, IL-1$\alpha$ and IL-1$\beta$ are two important members, and their concentrations are increased in the peritoneal fluid of patients with endometriosis. IL-1$\beta$ affects the proliferation of ectopic endometrial cells by regulating the expression of intercellular cell adhesion molecule (ICAM)-1 on cell surface (which can be recognized by NK cells after binding with lymphocyte function-associated antigen (LFA)-1 expressing lymphocytes) [120]. The decrease of soluble IL-1R2 receptor (a receptor with high affinity and inhibitory effect on IL-1$\beta$) in the peritoneal fluid of patients with endometriosis may cause the increase of IL-1$\beta$ concentration in the peritoneal environment [121]. IL-1$\beta$ not only regulates the proliferation of ectopic endometrial cells, but also promotes the vascularization of ectopic lesions by stimulating the release of VEGF and IL-6 [122]. In addition, IL-1 also has adverse effects on fertility, not only in its toxic effect on embryos [123], but also causes ovulation dysfunction in patients with endometriosis [124].

IL-2, a member of the chemokine family, is mainly produced by activated T lymphocytes and participates in cytotoxic cellular responses. Other functions include stimulating the proliferation and differentiation of lymphocytes, stimulating the proliferation and enhancing the killing activity of NK cells, inducing the production of lymphokine activated killers (LAKs), and activating monocytes and macrophages [125]. Different investigators have different views on the role of IL-2 in the development of endometriosis, as some studies have shown that the concentration of IL-2 in the peritoneal fluid of patients is reduced [126, 127, 128], while others have found the converse [93, 129]. A recent study showed that IL-2 is an independent protective factor against endometriosis [130]. In other words, the role of IL-2 in the pathogenesis of endometriosis is still unclear and more exploration is warranted.

IL-4 is a pleiotropic cytokine produced by Th2 cells [131]. Its biological effects mainly include stimulating the proliferation of B and T lymphocytes and promoting the differentiation of CD4${}^{+}$ T cells into Th2 cells [132, 133]. Increased IL-4 levels in peritoneal fluid of patients with mild endometriosis have been confirmed [134]. However, a contrary report suggests that the level of IL-4 in peritoneal fluid is not related to the presence or absence of endometriosis [135]. IL-4 mRNA and protein expression were increased in both peripheral monocytes and peritoneal fluid cells isolated from patients with endometriosis [136]. IL-4 produced in ectopic endometrial tissue can induce the proliferation of its stroma cells [137] probably through promoting the expression of Eotaxin mRNA in ectopic endometrial stroma in a dose-dependent manner, which promotes angiogenesis and subsequent development of endometriosis [137].

IL-6 is a multifunctional cytokine that is primarily produced in response to acute infection and tissue damage. It can regulate the growth and differentiation of a variety of cells, such as the induction of T lymphocyte activation and B lymphocyte differentiation [85]. While under normal circumstances, IL-6 expression is tightly regulated under pathological conditions, it may be continuously synthesized, affecting chronic inflammation and autoimmunity [138, 139]. It is well documented that the proliferation of MՓs in the peritoneal fluid of patients with endometriosis significantly increases IL-6 levels [140, 141, 142, 143, 144]. Elevated IL-6, by increasing haptoglobin, allows endometrial implants to evade peritoneal immune surveillance by reducing phagocytosis; NK cell activity can also be inhibited by IL-6 [140]. Other studies have found that endometrial stromal cells are resistant to IL-6 by reducing the expression of IL-6R [145, 146]. Elevated IL-6 in the peritoneal cavity not only facilitates the immune evasion of ectopic endometrial cells, but also regulates the growth of endometrial stromal cells.

IL-8, secreted by macrophages and monocytes, regulates inflammatory response by chemotaxis to neutrophils. It can also participate in neutrophil activation and have certain effects on eosinophils, basophils and lymphocytes [147]. It also has a strong proangiogenic effect and can be regarded as a potent angiogenic factor [85], contributing to cell adhesion [118]. IL-8 levels are increased in patients with endometriosis and may be positively correlated with disease severity [148, 149]. IL-8 can promote the proliferation of ovarian endometrioma-derived stromal cells, which may be enhanced by TNF-$\alpha$ [122].

IL-10 is a Th2-type cytokine, also secreted by other cells, such as MՓs, keratinocytes and tumor cells [150]. IL-10 regulates cell growth and differentiation, participates in inflammation and immune response, and mainly plays an inhibitory role. Studies found elevated levels of IL-10 in the peritoneal fluid of patients with endometriosis [98], which may be related to the decrease of NK cytotoxicity [151]. Locally elevated IL10 is more conducive to the entry of endometrial debris into the abdominal cavity, facilitating the early stage of pelvic endometriosis [152].

IL-13, secreted by Th2 cells and MCs, can act on Th2 cells, B lymphocytes and MՓs, thereby stimulated B cell differentiation and inhibiting the production of inflammatory factors from MՓs. Researchers found significantly lower levels of IL-13 in the peritoneal fluid of patients with endometriosis [153]. Further study found that the decrease in concentration of IL-13 was not related to the severity of the disease [154]. On the contrary, other studies suggest that the expression of IL-13 in the peritoneal fluid and endometriosis lesions of patients with endometriosis is increased [155], possibly related to its impaired fertility [156]. Therefore, the role of IL-13 in promoting or inhibiting the pathogenesis of endometriosis remains to be determined.

TNF-$\alpha$, mainly derived from the secretion of activated MՓs and T lymphocytes, plays a role in various necrosis or apoptosis-signaling pathways [157]. Studies have found that the concentration of TNF-$\alpha$ increased in peritoneal fluid of patients with endometriosis in stage I–II, but did not increase consistently with the progression of the disease [158]. TNF-$\alpha$ can lead to MՓs recruitment to the lesion site and differentiate into M1 type, triggering the recruitment of neutrophils to the peritoneal fluid [159], resulting cell adhesion between endometrial cells and peritoneum, stimulating the proliferation of stroma cells [160, 161], thereby promoting disease progression [162].

IFN-$\gamma$, a highly species-specific glycoprotein, is derived from activated T lymphocytes and NK cells. Its regulatory role on immune effects is mainly reflected in the activation of MՓs and development of T lymphocytes [163]. Whether the outcome of the response mediated by IFN is survival or apoptosis depends on the state of the cell at the time and the complex regulatory mechanisms. Maintaining Th1/Th2 balance also requires the participation of INF-$\gamma$ and IL-2 interaction. Studies have found that the level of IFN-$\gamma$ in the peritoneal fluid of women with endometriosis was elevated, with the Th1/Th2 balance skewed toward Th2 [90].

TGF-$\beta$, secreted by T lymphocytes, promotes the differentiation of Treg cells and Th17 cells to regulate immunity, and can also promote angiogenesis. Young et al. [164] pointed out that peritoneal mesothelial cells are also a source of TGF-$\beta$1 in patients with endometriosis through immunohistochemistry of peritoneal biopsy and in vitro study of peritoneal mesothelial cells. Studies have found that the activity of TGF-$\beta$ in peritoneal fluid of patients with endometriosis is increased, potentially related to the decreased activity of NK cells [113]. Further study found that peritoneal platelet-derived TGF-$\beta$1 downregulated NKG2D expression and thus suppressed NK cell activity [165]. These changes reduce the peritoneal immune surveillance function and prevent ectopic endometrial cells from phagocytosis. In vitro experiments showed that human endometrial cells were more likely to adhere to mouse peritoneum after TGF-$\beta$1 pretreatment. It was speculated that TGF-$\beta$1 may change the expression of cell surface adhesion molecules in peritoneal mesothelial cells or endometrial cells to promote their adhesion [166]. As a well-known epithelial to mesenchymal transition (EMT) inducer, TGF-$\beta$1 can increase the migration and invasion ability of endometrial epithelial cells by promoting EMT, thus realizing the implantation of endometrial cells [167]. TGF-$\beta$1 may activate the proliferation of ectopic endometrial stromal cells and promote disease progression by upregulating protease activated receptor 2 (PAR2) expression [168]. Vascularization is a necessary condition for the continued growth of the lesion. Young et al. [169] confirmed that TGF-$\beta$1 may increase the secretion of VEGF-A in the peritoneal mesothelium through the inhibitor of DNA-binding protein 1 (ID1) pathway, thus promoting the vascularization of endometriosis lesions. TGF-$\beta$ signaling has been shown to promote the activation of M2 type MՓs, a state conducive to the development of endometriosis [170]. In addition, the decrease of NK cell activity induced by TGF-$\beta$ may affect mouse embryonic development, resulting in infertility [171].

VEGF can not only increase vascular permeability and promote the deformation of extracellular matrix, but also make vascular endothelial cells migrate and proliferate, and promote angiogenesis. Endometriosis is characterized by the presence of numerous vascular proliferations in and around endometriotic lesions. It is generally believed that the formation of numerous new blood vessels is related to the etiology of endometriosis [162]. This is also confirmed by the increased VEGF levels found in the peritoneal fluid of patients with endometriosis [101], but it has yet to be verified whether these high concentrations of VEGF originate from the ectopic lesions themselves [172, 173] or from activated MՓs [37]. Thus, researchers speculate that the elevated level of VEGF in peritoneal fluid has notable clinical significance in the progression of the disease.