Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights.

Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube.

The influence of hydrosalpinx on markers of endometrial receptivity.

Hydrosalpinx is a common condition among women of reproductive age. It is related to low pregnancy rates in the settings of in vitro fertilization-embryo transfer programs. Such low rates are not yet well understood, and may be due to poor endometrial receptivity and abnormal expression of key molecules in the endometrium that are important for implantation. The available data on the inflammatory response, endometrial blood flow, integrins, leukemia inhibitory factor, matrix metalloproteinases, and homeobox gene A10 expression in the presence of hydrosalpinx are reviewed. In addition, the evidence for treatment options to improve pregnancy rates is also discussed.

Chlamydia trachomatis enhances the expression of matrix metalloproteinases in an in vitro model of the human fallopian tube infection.

OBJECTIVE: The sequelae of sexually transmitted Chlamydia trachomatis infection include fallopian tube scarring, which implies modification of the extracellular matrix. Our objective was to describe the production of two matrix metalloproteinases in response to chlamydial infection in vitro. STUDY DESIGN: Human fallopian tube organ cultures were infected with Chlamydia, and the production of matrix metalloproteinases was assessed by gelatin zymography, antigen capture enzyme-linked immunosorbent assay, immunohistochemistry, and in situ zymography. RESULTS: Significantly elevated levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were found in supernatants of infected segments. Immunohistochemistry and in situ zymography revealed that epithelial cells tended toward matrix metalloproteinase-2 production and that matrix metalloproteinase-9 exhibited a more diffuse stromal staining pattern. CONCLUSION: Matrix metalloproteinase-2 and matrix metalloproteinase-9 are expressed in vitro in response to chlamydial infection. Enhanced matrix metalloproteinase production in some individuals in response to infection may lead to tubal scarring through the increased turnover and subsequent repair of the extracellular matrix.

Effect of hydrosalpinx fluid on secretion of trophoblastic matrix metalloproteinases.

OBJECTIVE: To determine if hydrosalpinx fluid affects trophoblastic metalloproteinases (MMPs) secretion. DESIGN: Measurement of the effect of hydrosalpinx and peritoneal fluids (as controls) added to the medium on the MMPs secreted by cytotrophoblastic cells. SETTING: Academic research center. PATIENT(S): Five samples of hydrosalpinx fluid were obtained at the time of ovocyte retrieval. Three samples of peritoneal fluids were collected at laparoscopic sterilization. MAIN OUTCOME MEASURE(S): The concentration and activity of MMP-2 and MMP-9, the concentration of the tissue inhibitor of metalloproteinases (TIMP-1), and the total gelatinolytic activity of the cytotrophoblastic cells were measured in the culture medium. RESULT(S): Hydrosalpinx significantly stimulated MMP-2, MMP-9, and TIMP-1. The net result was a significant stimulation of the total gelatinolytic activity. Peritoneal fluids increased MMP-2, MMP-9, and TIMP-1 concentrations, but the total gelatinolytic activity was not modified. CONCLUSION(S): In contrast to peritoneal fluids, hydrosalpinx stimulates the total gelatinolytic activity of cytotrophoblastic cells. This might indicate that the effect of hydrosalpinx on implantation rates may not be due to an inhibition of the capacity of an embryo to invade the endometrium. However, the stimulatory effect of hydrosalpinx on the net gelatinolytic activity could partly explain the increased incidence of ectopic pregnancies that have been described in the presence of hydrosalpinx.

Semen granulocyte elastase: its relevance for the diagnosis and prognosis of silent genital tract inflammation.

Elastase-inhibitor complex was assessed by immunoassay in the seminal plasma of 312 men attending the outpatient infertility clinic. Using receiver operating characteristic (ROC) curve analysis, elastase at the cut-off value of > or =290 ng/ml was shown to be efficient (sensitivity 79.5%, specificity 74.4%) in the detection of genital tract inflammation as defined by leukocytospermia (>1x10(6) leukocytes/ml). The prevalence of increased elastase in 292 infertile men was significantly higher (34%) as compared with that (5%) observed in 20 fertile men (P: = 0.02). Moreover, high elastase concentration (> or =290 ng/ml) was observed in 66 of the 264 men (25%) without leukocytospermia. A significant positive correlation was found between elastase concentration and patient age (r = 0.202, P: < 0.0001) and the number of leukocytes (r = 0.330, P: < 0.0001). A negative correlation was found between elastase concentration and semen volume (r = -0.146, P: = 0.01) and the percentage of spermatozoa with single-stranded DNA (r = -0.194, P: = 0.024), but there was no correlation between elastase and sperm reactive oxygen species production. A higher seminal elastase concentration was significantly associated with tubal damage in female partners (P: < 0.001). After norfloxacine antibiotic therapy, decrease in elastase concentration was observed in 15 (25%) of the 60 treated patients. Tubal damage in the partner negatively affected the response to antibiotic therapy. In conclusion, granulocyte elastase is a reliable screening test for silent genital tract inflammation of the couple. The elastase-inhibitor complex may have a protective effect in reducing sperm DNA denaturation.