The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Pseudocarcinomatous Hyperplasia of Tubal Mucosa Associated With Chronic Salpingitis - Clinical And Pathological Challenge: A Case Report.

Pseudocarcinomatous hyperplasia of the tubal mucosa is a rare, reactive response to an underlying inflammatory or neoplastic process. We present a case of pseudocarcinomatous hyperplasia in a 26-year-old woman with clinical symptomatology of pelvic inflammatory disease, and a normal serum Ca 125-level (30 U/ml). The ultrasound finding showed presence of hydrosalpinx characterized with unilateral tubal enlargement in sausage-like shape that arose from the upper lateral margin of the uterus. The young age of the patient, presence of chronic inflammation, epithelial hyperplasia with unremarkable nuclear atypia and mitosis facilitated the right diagnosis. Pseudocarcinomatous hyperplasia can mimic neoplastic processes clinically and pathologically. Differential morphological and clinical features should be considered to ensure accurate diagnosis and proper management.

Effects of salpingitis simulation on the morphology and expression of inflammatory-related genes of oviduct in laying hens.

This study was conducted to simulate salpingitis of laying hens by observing the morphology and expression of inflammatory genes in the oviduct. A total of one hundred twenty 81-wk-old Roman Pink laying hens in good physical condition without the oviduct disease with an average egg production rate of 76% were fed a basal diet for 2 wks and then randomly allocated into 4 groups (6 replicates/group, 5 birds/replicate). The experimental treatments were as follows: 1) Control group (treated with PBS); 2) Organic chemical reagent (OCR) group; 3) Lipopolysaccharide (LPS) group; 4) LPS + OCR group. First, the chickens were kept upside down to make ectropion and exposure of the apertura uterinae; then prepared reagents were poured into the uterine part of the fallopian tube by using the chicken vas deferens (1 mL/layer); finally, the chickens were kept in the inverted position for 5 to 10 min. The fallopian tube samples (the magnum, isthmus, and uterus) were collected after 48 h of treatment. Compared with the control, treatment with LPS+OCR decreased (P < 0.05) the secondary villus length and primary villus area in magnum and villus length in isthmus (P < 0.05). An increase (P < 0.05) of the intervillous space of uterus was observed in LPS + OCR group compared with the control. The expressions of interleukin-6 mRNA of magnum and interferon-γ (IFN-γ) of isthmus in the LPS and LPS+OCR treatments were higher (P < 0.05) than that in control. Compared with the control, treatment with LPS+OCR increased (P < 0.05) the expressions of IFN-γ mRNA of magnum and IFN-γ, tumor necrosis factor-α and inducible nitric oxide synthase mRNA of uterus in laying hens. In conclusion, the results of morphological damage of fallopian tube tissue and increased expression of inflammatory factors in LPS + OCR treatment group suggested that LPS+OCR treatment can provide data basis to establish salpingitis model in laying hens for studying the pathogenesis of it.

Bovine salpingitis: Histopathology, bacteriology, cytology and transcriptomic approaches and its impact on the oocyte competence.

The present study was performed to examine the histopathology, cytology, bacteriology and expression pattern of a targeted set of genes of cytokines in the oviduct of cows with inflammation (Experiment 1). In addition, the effects of oviductal fluid from cows with salpingitis on the oocyte maturation and fertilization in vitro were examined (Experiment 2). The most frequent bacterial co-infection was Escherichia coli and Fusobacterium necrophorum, which was always associated with severe histopathologic salpingitis. Out of 15 cows with histologically healthy uterus, only one cow (6.7%) displayed the histologic signs of mild salpingitis, whereas from 50 cows with endometritis, 48 cows (96%) showed histologically different grades of salpingitis. The mRNA expression of IL1ß, CD14, IL8 and CASP3 was significantly different among all groups of salpingitis (P < 0.05) with the highest level of mRNA expression in the sever grade of salpingitis. Results of experiment 2 showed a significant decline in the oocytes with peripheral free mitochondria and fertilization rate in the salpingitis group than the no- salpingitis group (P < 0.05). In conclusion, our results showed that histologically detected salpingitis is in most cases associated with histologic and cytologic endometritis. The pattern of the gene expression of chemokines and cytokines was altered in association with different grades of salpingitis. Further, we observed a decline in the peripherally located mitochondria and lower fertilization rate in oocytes following addition of oviductal fluid collected from the cows with sapingitis to the maturation media.

The immune cell profile of human fallopian tubes in health and benign pathology: a systematic review.

The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8+ T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.

Xanthogranulomatous salpingo-oophoritis presenting as an ovarian tumour.

Xanthogranulomatous salpingo-oophoritis (XGSO) is an exceptionally rare entity. Its clinical manifestations and imaging modalities can mimic benign and malignant adnexal diseases, making it difficult to diagnose. Here we report a case of XGSO in a young woman who was operated with suspicion of a borderline ovarian tumour. Preoperative diagnosis of XGSO should be considered to avoid radical surgical treatment, especially in young patients.

Characterization of Pathogenic CD8+ T cells in Chlamydia-Infected OT1 Mice.

Chlamydia trachomatis is a leading infectious cause of infertility in women due to its induction of lasting pathology such as hydrosalpinx. Chlamydia muridarum induces mouse hydrosalpinx because C. muridarum can both invade tubal epithelia directly (as a first hit) and induce lymphocytes to promote hydrosalpinx indirectly (as a second hit). In the current study, a critical role of CD8+ T cells in chlamydial induction of hydrosalpinx was validated in both wild type C57BL/6J mice and OT1 transgenic mice. OT1 mice failed to develop hydrosalpinx partially due to the failure of their lymphocytes to recognize chlamydial antigens. CD8+ T cells from naive C57BL/6J mice rescued the ability of recipient OT1 mice to develop hydrosalpinx when naive CD8+ T cells were transferred at the time of infection with Chlamydia. However, when the transfer was delayed for 2 weeks or longer after the Chlamydia infection, naive CD8+ T cells no longer promoted hydrosalpinx. Nevertheless, CD8+ T cells from mice immunized against Chlamydia still promoted significant hydrosalpinx in the recipient OT1 mice even when the transfer was delayed for 3 weeks. Thus, CD8+ T cells must be primed within 2 weeks after Chlamydia infection to be pathogenic, but, once primed, they can promote hydrosalpinx for >3 weeks. However, Chlamydia-primed CD4+ T cells failed to promote chlamydial induction of pathology in OT1 mice. This study optimized an OT1 mouse-based model for revealing the pathogenic mechanisms of Chlamydia-specific CD8+ T cells.

The Continued Challenges in the Diagnosis of Acute Pelvic Inflammatory Disease: Focus on Clinically Mild Disease.

Many women with lower genital tract infections associated with sexually transmitted pathogens have evidence of upper genital tract inflammation despite the absence of symptoms and signs traditionally associated with pelvic inflammatory disease (PID). New biomarkers are needed to identify these women with clinically mild PID or subclinical PID (silent salpingitis) to facilitate initiation of early treatment and ameliorate the sequelae associated with upper genital tract infection and inflammation.

Ruptured salpingitis isthmica nodosa: a rare cause for spontaneous haemoperitoneum.

Salpingitis isthmica nodosa (SIN) is the nodular swelling or diverticulum of the isthmus of the fallopian tube. It is most commonly identified when investigating female infertility or in association with ruptured ectopic pregnancies. We experienced a rare and atypical presentation of SIN. A 33-year-old woman presented with a 1-hour history of acute lower abdominal pain associated with nausea and vomiting. CT and pelvic ultrasound revealed haemoperitoneum with no radiological evidence for its aetiology. Initial beta-human chorionic gonadotropin excluded ectopic pregnancy. A diagnostic laparoscopy was performed following clinical deterioration of the patient. Active bleeding of the right fallopian tube was identified and managed with a right partial salpingectomy, with subsequent histopathology revealing ruptured SIN. There have been no reported cases of SIN being a primary cause for an acute abdomen or haemoperitoneum in the absence of an ectopic pregnancy, making this case a surgical novelty.

Recurrent Bilateral Salpingitis in a Sexually Inactive Adolescent: Don't Forget about the Appendix.

BACKGROUND: Salpingitis is an acute inflammation of the fallopian tubes and is extremely uncommon in patients who are sexually inactive or premenarchal. CASE: We describe a 15-year-old sexually inactive patient with recurrent bilateral salpingitis. After the second episode, she underwent an exploratory laparoscopy and was diagnosed with chronic appendicitis. SUMMARY AND CONCLUSION: Appendicular involvement should be kept in mind in recurrent salpingitis episodes, especially if previous imaging studies do not show signs of appendicitis. Imaging studies should be repeated in experienced centers in case of recurrent episodes. Laparoscopy is the gold standard for the diagnosis of salpingitis and can confirm appendicular or other abdominal involvement. Early diagnosis can help to prevent recurrent episodes of salpingitis and thus reduce the risk of sequelae.

Suppression of Chlamydial Pathogenicity by Nonspecific CD8+ T Lymphocytes.

Chlamydia trachomatis, a leading infectious cause of tubal infertility, induces upper genital tract pathology, such as hydrosalpinx, which can be modeled with Chlamydia muridarum infection in mice. Following C. muridarum inoculation, wild-type mice develop robust hydrosalpinx, but OT1 mice fail to do so because their T cell receptors are engineered to recognize a single ovalbumin epitope (OVA457-462). These observations have demonstrated a critical role of Chlamydia-specific T cells in chlamydial pathogenicity. In the current study, we have also found that OT1 mice can actively inhibit chlamydial pathogenicity. First, depletion of CD8+ T cells from OT1 mice led to the induction of significant hydrosalpinx by Chlamydia, indicating that CD8+ T cells are necessary to inhibit chlamydial pathogenicity. Second, adoptive transfer of CD8+ T cells from OT1 mice to CD8 knockout mice significantly reduced chlamydial induction of hydrosalpinx, demonstrating that OT1 CD8+ T cells are sufficient for attenuating chlamydial pathogenicity in CD8 knockout mice. Finally, CD8+ T cells from OT1 mice also significantly inhibited hydrosalpinx development in wild-type mice following an intravaginal inoculation with Chlamydia Since T cells in OT1 mice are engineered to recognize only the OVA457-462 epitope, the above observations have demonstrated a chlamydial antigen-independent immune mechanism for regulating chlamydial pathogenicity. Further characterization of this mechanism may provide information for developing strategies to reduce infertility-causing pathology induced by infections.

Whole genome sequence comparison of avian pathogenic Escherichia coli from acute and chronic salpingitis of egg laying hens.

BACKGROUND: Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity. RESULTS: From the core- and accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis. CONCLUSION: Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.

Adrenomedullin insufficiency alters macrophage activities in fallopian tube: a pathophysiologic explanation of tubal ectopic pregnancy.

Ectopic pregnancy is the major cause of maternal morbidity and mortality in the first trimester of pregnancy. Tubal ectopic pregnancy (TEP) accounts for nearly 98% of all ectopic pregnancies. TEP is usually associated with salpingitis but the underlying mechanism in salpingitis leading to TEP remains unclear. Adrenomedullin (ADM) is a peptide hormone abundantly expressed in the fallopian tube with potent anti-inflammatory activities. Its expression peaks at the early luteal phase when the developing embryo is being transported through the fallopian tube. In the present study, we demonstrated reduced expression of ADM in fallopian tubes of patients with salpingitis and TEP. Using macrophages isolated from the fallopian tubes of these women, our data revealed that the salpingistis-associated ADM reduction contributed to aggravated pro-inflammatory responses of the tubal macrophages resulting in production of pro-inflammatory and pro-implantation cytokines IL-6 and IL-8. These cytokines activated the expression of implantation-associated molecules and Wnt signaling pathway predisposing the tubal epithelium to an adhesive and receptive state for embryo implantation. In conclusion, this study provided evidence for the role of ADM in the pathogenesis of TEP through regulating the functions of tubal macrophages.

Xanthogranulomatous Salpingitis.

There are approximately a dozen cases of xanthogranulomatous salpingitis reported in the literature, mostly as case reports. Thirteen such cases were identified from 2003 to 2018 at our institution. Patient's ages ranged from 21 to 75 yr old (median and mean, 49 yr). Clinical presentations and surgical indications included pelvic inflammatory disease (5 cases), endometrial carcinoma (4 cases), suspicion of ovarian malignancy (1 case), symptomatic fibroids (1 case), endometriosis (1 case), and infertility (1 case). Surgical-pathologic correlation resulted in diagnoses of tubo-ovarian abscess (4 cases), ovarian abscess (2 cases), pyosalpinx (2 cases), and chronic endometritis (2 cases). Of the remaining 3 cases, 2 presented clinically as pelvic inflammatory disease and the other was seen in the context of an endometrial carcinoma. In summary, this case series from a single institution shows that xanthogranulomatous salpingitis is an uncommon form of chronic inflammation that may be diagnosed from reproductive to menopausal age. With one exception, the cases in this series represent pelvic inflammatory disease despite variable clinical presentations. Pseudoxanthomatous salpingitis should be in the differential diagnosis.

Peritoneal involvement by salpingoliths clinical significance and cytological challenges of interpretation.

We present a case of salpingoliths detected in peritoneal washing, during an elective bilateral salpingo-oophorectomy, in a 32 years old woman with history of familial BRCA gene mutation. Salpingoliths are psammoma body-like types of calcification that originate from the fallopian tubes and can be encountered in peritoneal washings. Unlike psammoma bodies, salpingoliths have been tagged to benign and hyperplastic processes more often than neoplastic processes. Misinterpreting salpingoliths as psammoma bodies in peritoneal washings can be misleading for both cytopathologists and clinicians, especially as in the presented case, where there is a high risk for ovarian carcinoma. In this article, we aim to shed light on this rare finding, and report theories explaining its pathogenesis, in addition we provide an example of its challenging cytological presentation, to increase awareness among cytopathologists.

Salpingitis Impairs Bovine Tubal Function and Sperm-Oviduct Interaction.

Salpingitis is a common cause for subfertility and infertility both in humans and animals. However, the effects of salpingitis on tubal function and reproductive success are largely unknown. Therefore we set out to investigate the effects of inflammation on sperm and oocyte transport and gameto-maternal interaction in the oviduct using the bovine as a model. For this purpose, oviducts revealing mild (n = 45), moderate (n = 55) and severe (n = 45) inflammation were obtained from cows immediately after slaughter and investigated by live cell imaging, histochemistry and scanning electron microscopy. Our studies showed that endometritis was always correlated with salpingitis. Moderate and severe inflammation caused a significant increase in the thickness of tubal folds (p < 0.05). Severe inflammation was characterized by luminal accumulations of mucus and glycoproteins, increased apoptosis, loss of tight junctions and shedding of tubal epithelial cells. The mean ciliary beat frequency (CBF) in the ampulla was significantly reduced as compared to the controls (p < 0.05). The higher the grade of inflammation, the lower was the CBF (p < 0.001). In severe inflammation, spermatozoa were stuck in mucus resulting in decreased sperm motility. Our results imply that tubal inflammation impairs proper tubal function and leads to reduced sperm fertilizing capacity.

Histopathologic Features of Postablation Tubal Sterilization Syndrome.

Postablation tubal sterilization syndrome (PATSS) is an uncommon complication of endometrial ablation in patients with antecedent tubal ligation characterized by cyclic pelvic pain. Recurrent tubal distention resulting from retrograde menstruation into occluded proximal fallopian tube segments by residual/regenerated cornual endometrial tissue is postulated to be the cause. Reports of PATSS have largely focused on the clinicoradiologic and operative findings. Detailed descriptions of the gross pathologic findings of PATSS are sparse and rarer still are examples in which the histologic manifestations are discussed. Three patients with a history of tubal ligation and subsequent endometrial ablation who underwent hysterectomy and bilateral salpingo-oophorectomy for pelvic pain were identified. A clinical suspicion of PATSS was conveyed to the pathologist at the time of initial pathologic examination in only 2 of the 3 cases. Pathologic findings in all 3 cases were similar and included hematosalpinx of the proximal fallopian tubes, intraluminal hemosiderotic material, mural hemosiderosis, and pseudoxanthomatous salpingitis featuring plical and mural lipofuscin-laden macrophages, along with inactive to attenuated endometrium with variable submucosal myometrial hyalinization/scarring compatible with postablative changes. The pathologic features, in conjunction with the appropriate clinicoradiologic findings, were interpreted as consistent with PATSS. PATSS complicates an estimated 5% to 10% of endometrial ablations, but is likely underreported due to a lack of awareness. Pathologists should consider PATSS in hysterectomy specimens that show postablative endometrial changes accompanied by hematosalpinx and pseudoxanthomatous salpingitis of the proximal segments of ligated fallopian tubes. To our knowledge, this is the first study to depict the histopathologic features of PATSS.

Tracing GFP-labeled WJMSCs in vivo using a chronic salpingitis model: an animal experiment.

BACKGROUND: The present study was conducted to evaluate the distribution of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) and their repairing function on the oviduct. METHODS: WJMSCs were transfected with the LV3-GFP-PURO lentivirus. Female New Zealand rabbits (n = 24) were divided randomly into control A and B groups and experimental C and D groups to establish inflammation models. Sterile saline solution or WJMSCs were injected into rabbits via ear veins and/or genital tract perfusion once weekly for 3 weeks. All rabbits were humanely sacrificed 1 week after the last perfusion to collect the oviduct, uterus, liver, and bladder for examination. Green fluorescent protein (GFP) and cytokeratin 7 (CK7) were imaged using a Leica Qwin Plus V3 fluorescence confocal microscope and analyzed as mean optical densities in an Image-Pro Plus analysis system. RESULTS: We found that lentivirus expressing the GFP gene produced an efficient transfection. The mean optical density values of GFP and CK7 in the oviducts were higher in the experimental D group than those in the control A and experimental C groups. No GFP fluorescence deposits occurred in the bladder of the control A group or experimental C group. Colocalization of CK7 and WJMSCs was observed in the oviducts in all groups. CONCLUSIONS: WJMSCs exhibited homing characteristics and migrated to the injured oviduct to promote epithelial cell growth. Additionally, local treatment resulted in higher efficiency.

Salpingitis y ooforitis xantogranulomatosa: presentación de 2 casos / Xanthogranulomatous salpingitis and oophoritis: a report of 2 cases

La salpingitis xantogranulomatosa es un proceso inflamatorio poco frecuente, caracterizado por un infiltrado de la mucosa por tejido inflamatorio de granulación conteniendo histiocitos de citoplasma espumoso. Este tipo de inflamación es excepcional a nivel del tracto genital femenino y clásicamente se ha asociado a infecciones bacterianas crónicas, inmunosupresión u otras causas de inflamación crónica. Pero también se ha visto en relación con el carcinoma endometrial, la endometriosis, cuerpos extraños y enfermedad inflamatoria pélvica crónica. El hecho de que acompañe o no a endometriosis genital ha llevado a la diferenciación de 2 tipos de entidades: la salpingitis xantogranulomatosa, sin endometriosis acompañante, y la salpingiosis pseudoxantomatosa. Presentamos 2 casos con su histología e inmunohistoquímica, y se ha revisado la literatura sobre este tipo de inflamaciones crónicas (AU)

Xanthogranulomatous salpingitis is an uncommon inflammatory process, characterized by an infiltration of the mucous by inflammatory granulation tissue with foamy histiocytes. This kind of inflammation is exceptional in the female genital tract; classically, it has been associated with chronic bacterial infections, immunosuppression and other causes of chronic inflammation. However, it has also been found associated with endometrial carcinoma, endometriosis, foreign bodies and chronic pelvic inflammatory disease. As this inflammation may or may not be accompanied by genital endometriosis, 2 entities have been differentiated: xanthogranulomatous salpingitis without endometriosis and pseudoxanthomatous salpingitis. We present 2 cases of this type of chronic inflammation, including immunohistochemistry findings, and we review the pertinent literature (AU)

Uterotubal junction prevents chlamydial ascension via innate immunity.

Ascension to the oviduct is necessary for Chlamydia to induce tubal infertility. Using the Chlamydia muridarum induction of hydrosalpinx mouse model, we have demonstrated a significant role of the uterotubal junction in preventing chlamydial ascending infection. First, delivery of C. muridarum to either side of the uterotubal junction resulted in significant reduction in live organisms from the tissues on the opposite sides. However, the recovery yields remained similar among different sections of the uterine horn. These observations suggest that the uterotubal junction may function as a barrier between the uterine horn and oviduct. Second, deficiency in innate immunity signaling pathways mediated by either MyD88 or STING significantly compromised the uterotubal junction barrier function, permitting C. muridarum to spread freely between uterine horn and oviduct. Finally, transcervical inoculation of C. muridarum led to significantly higher incidence of bilateral hydrosalpinges in the STING-deficient mice while the same inoculation mainly induced unilateral hydrosalpinx in the wild type mice, suggesting that the STING pathway-dependent uterotubal junction plays a significant role in preventing tubal pathology. Thus, we have demonstrated for the first time that the uterotubal junction is a functional barrier for preventing tubal infection by a sexually transmitted agent, providing the first in vivo evidence for detecting chlamydial infection by the STING pathway.