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Objective: Assess risk factors for incident and endometrial Mycoplasma genitalium infection and determine if M. genitalium is associated with histological endometritis, an indicator of pelvic inflammatory disease.Methods: This study was a secondary data analysis within the T cell Response Against Chlamydia (TRAC) Study, a prospective evaluation of 246 women with or at risk for Chlamydia trachomatis from urban outpatient clinics, who were followed quarterly for 12 months. Risk factors for incident M. genitalium infection were determined by Cox regression. Relative risks were estimated by Poisson regression with robust error measurements for models examining the association between M. genitalium and endometritis (histological evidence of plasma cells in endometrial stroma and neutrophils in the endometrial epithelium) and for models examining risk factors for detection of endometrial M. genitalium infection.Results: M. genitalium prevalence was 16.7%, incidence was 25.3 per 100 person-years and 23% had repeated positive tests. Black race (non-black HRadj 0.4, 95% CI 0.2 to 0.9), less education (HRadj 2.4, 95% CI 1.2 to 5.1) and a new sexual partner (HRadj 3.1, 95% CI 1.7 to 5.4) were associated with incident M. genitalium. M. genitalium was associated with endometritis (RRadj 2.0, 95% CI 1.1 to 3.7). Trichomonas vaginalis (RRadj 2.0, 95% CI 1.2 to 3.4) and endometrial C. trachomatis (RRadj 1.7, 95% CI 1.1 to 2.8) were associated with endometrial M. genitalium.Conclusions: M. genitalium is prevalent in women at high risk for C. trachomatis, persists over multiple follow-up visits and is associated with histological endometritis. Studies are needed to determine if screening for M. genitalium will improve reproductive outcomes. [ABSTRACT FROM AUTHOR]

Problem: Toll‐like (TLR) receptor genetic variants have been implicated in bacterial vaginosis (BV). We determined whether TLR variants are associated with fastidious BV‐associated microbes that are linked with infertility following pelvic inflammatory disease (PID). Method of study: Sneathia spp., Atopobium vaginae, BVAB1, and Ureaplasma urealyticum were measured in 250 women from the PID Evaluation and Clinical Health (PEACH) study. Relative risk (RR) and 95% confidence intervals (CI) were calculated adjusting for chlamydia and gonorrhea. Principal component analysis was used to adjust for population stratification. A false discovery rate q‐value of 0.05 was significant. Results: TLR2‐1733C>A (P = .003) and TLR2‐616A>G (P = .004) were associated with cervical A. vaginae. TLR2‐1733C>A and TLR6‐438C>T were associated with A. vaginae detection in the endometrium, but this was not significant after adjustment for multiple comparisons (FDR q‐value = 0.06). Conclusion: Host gene variants in TLR2 signaling pathways were modestly associated with cervical A. vaginae in women with clinical PID. [ABSTRACT FROM AUTHOR]

Background: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.Presentation Of the Hypothesis: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.Testing the Hypothesis: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.Implications Of the Hypothesis: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis. [ABSTRACT FROM AUTHOR]

Objectives As inflammation has been associated with preeclampsia in cross-sectional analyses, we examined the relationship between inflammatory markers and preeclampsia in early pregnancy. Methods We conducted a nested case-control study of 409 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort at a median gestation of 16 weeks. Preeclampsia was defined by blood pressure ⩾140/90 mmHg and proteinuria ⩾3 g/24 h. Inflammatory markers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-alpha, TNF-beta, TNF-receptor, IL-1beta IL-1alpha IL-8, IL-10, IFN-gamma, IL-18, macrophage migration inhibitory factor (MIF), macrophage inflammatory protein (MIP), transforming growth factor-beta (TGF), and RANTES. We examined associations between inflammatory markers dichotomized by the limit of detection (LOD) and preeclampsia using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Models were adjusted for body mass index (BMI) and smoking. Results Women with IL-6 (OR 1.44, 95% CI 1.03–2.03) and TNF-alpha (OR 1.54, 95% CI 1.06–2.23) levels above the LOD have significantly increased risk of preeclampsia. IL-1beta levels above the LOD showed a decreased risk of preeclampsia (OR 0.55, 95% CI 0.3–1.01). Conclusions Elevated inflammatory markers in early pregnancy may be markers of subclinical disease and/or may be involved in pathogenesis. As these relationships are complex future studies should explore cytokine clusters in preeclampsia risk. Disclosures B.D. Taylor: None. G. Tang: None. R.B. Ness: None. J. Olsen: None. D.M. Hougaard: None. K. Skogstrand: None. J.M. Roberts: None. C. Haggerty: None. [ABSTRACT FROM AUTHOR]

Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted by both human and bacterial cells. Human and bacterial EVs (BEVs) propagate and transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues by bacterial cells is not required for immunogenic stimulation. This phenomenon is important in the feto-maternal interface, where optimum tolerance between the mother and fetus is required for a successful pregnancy. Though the intrauterine cavity is widely considered sterile, BEVs from diverse sources have been identified in the placenta and amniotic cavity. These BEVs can be internalized by human cells, which may help them evade host immune surveillance. Though it appears logical, whether bacterial cells internalize human EVs or human EV cargo is yet to be determined. However, the presence of BEVs in placental tissues or amniotic cavity is believed to trigger a low-grade immune response that primes the fetal immune system for ex-utero survival, but is insufficient to disrupt the progression of pregnancy or cause immune intolerance required for adverse pregnancy events. Nevertheless, the exchange of bioactive cargos between human and BEVs, and the mechanical underpinnings and health implications of such interactions, especially during pregnancy, are still understudied. Therefore, while focusing on the feto-maternal interface, we discussed how human cells take up BEVs and whether bacterial cells take up human EVs or their cargo, the exchange of cargos between human and BEVs, host cell (feto-maternal) inflammatory responses to BEV immunogenic stimulation, and associations of these interactions with fetal immune priming and adverse reproductive outcomes such as preeclampsia and preterm birth., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

Study Hypothesis: In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture., Study Finding: We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation., What Is Known Already: Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM., Study Design, Samples/materials, Methods: Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups., Main Results and the Role of Chance: Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence., Limitations, Reasons for Caution: Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM., Wider Implications of the Findings: Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome., Study Funding and Competing Interests: This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of Texas Medical Branch at Galveston and funds to Dr M. Kacerovský from the Ministry of Health Czech Republic (UHHK, 001799906). The authors report no conflict of interest., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)