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Background The comprehensive impact of human papillomavirus (HPV) infection on reproductive tract inflammation and adverse pregnancy outcomes among women of reproductive age has not been fully investigated. Methods A retrospective cohort study was conducted among women presenting to the gynecological departments of specialized women’s hospitals in Ningbo, China, between 2016 and 2020. A total of 6506 women, with an average age of 28.7 years, who had undergone HPV testing and genotyping were included in the study. Results Overall, the most prevalent HPV types were HPV 52 (25.8%), HPV 16 (17.9%), and HPV 58 (7.7%). Vaginitis and cervicitis were significantly more prevalent in women with high-risk HPV (HR-HPV) compared to those with low-risk HPV(LR-HPV) (9.0% vs. 4.7%; 10.8% vs.7.1%; P  < 0.05). Moreover, the incidence of cervicitis in patients with persistent HPV infection for more than two years was significantly higher than in those with HPV infection for one year (21.8% vs. 11.8%; P  < 0.05). Pregnant women with HR-HPV infection had a significantly increased risk of miscarriage (9.7% vs. 6.1%; P  < 0.05). Our cross-sectional analysis of potential risk factors for HPV infection during pregnancy revealed that higher pregnancy glucose levels (prevalence, 4.23%; OR, 1.10; 95% CI, 1.10–1.20; P  < 0.05) significantly increased the risk of HPV infection. Women with persistent HR-HPV infection had a significantly higher risk of reproductive tract inflammation and adverse pregnancy outcomes. The analysis revealed significant associations between HPV infection and several pregnancy outcomes, including an increased risk of miscarriage, reduced live birth rate, and a higher cesarean section rate. Conclusions This highlights the need to monitor gestational glucose levels, reproductive tract inflammation, and HPV infection to reduce the risk of adverse pregnancy outcomes among pregnant women.

Background. Diagnosis and treatment of sexually transmitted infections (STIs) is a public health priority, particularly in regions where the incidence of human immunodeficiency virus (HIV) infection is high. In most developing countries, STIs are managed syndromically. We assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women. Methods. HIV-uninfected high-risk women (n = 242) were followed for 24 months. Symptoms of STIs were recorded, and laboratory diagnosis of common STI pathogens was conducted every 6 months. Forty-two cytokines were measured by Luminex in cervicovaginal lavage specimens at enrollment. Human immunodeficiency virus type 1 (HIV-1) infection was evaluated monthly. Results. Only 12.3% of women (25 of 204) who had a laboratory-diagnosed, discharge-causing STI had clinically evident discharge. Vaginal discharge was thus a poor predictor of laboratory-diagnosed STIs (sensitivity, 12.3%; specificity, 93.8%). Cervicovaginal cytokine concentrations did not differ between women with asymptomatic STIs and those with symptomatic STIs and were elevated in women with asymptomatic STIs, compared with women with no STIs or bacterial vaginosis. Although laboratory-diagnosed STIs were associated with increased risk of HIV infection (hazard ratio, 3.3 [95% confidence interval, 1.5—7.2)], clinical symptoms were not. Conclusions. Syndromic STI diagnosis dependent on vaginal discharge was poorly predictive of laboratory-diagnosed STI. Laboratory-diagnosed STIs were associated with increased susceptibility to HIV acquisition, while vaginal discharge was not.

It has been long understood that the vaginal microflora is crucial in maintaining a normal physiological environment for the host and its involvement is deemed indispensable for reproductive success. A global concept of normalcy vs. dysbiosis of vaginal microbiome is debatable as women of different races have a unique vaginal microflora with regional variations. Vaginal microflora is a dynamic microenvironment affected by gestational status, menstrual cycle, sexual activity, age, and contraceptive use. Normal vaginal flora is dominated by lactobacilli especially in women of European descent vs. African American women. These microbes confer the host vagina protection from potentially pathogenic microbes that may lead to urinary tract infections and sexually transmitted diseases. Changes in the vaginal microbiota including reduced lactobacilli abundance and increased facultative and anaerobic organism populations result in bacterial vaginosis, that predisposes the host to several conditions like low birth weight and increased risk of contracting bacterial infections. On the other hand, the vaginal microbiome is also reshaped during pregnancy, with less microbial diversity with a dominance of Lactobacillus species. However, an altered vaginal microbiota with low lactobacilli abundance especially during pregnancy may result in induction of excessive inflammation and pre-term labor. Since the vaginal microbiome plays an important role during embryo implantation, it is not surprising that bacterial vaginosis is more common in infertile women and associated with reduced rates of conception. Probiotic has great success in treating bacterial vaginosis and restoring the normal microbiome in recent. This report, reviewed the relationships between the vaginal microbiome and women’s reproductive health.

Endometritis is the most common bovine uterine disease following parturition. The role of prostaglandin E2 (PGE2) in the regulation of endometrial inflammation and repair is well understood. Excess PGE2 is also generated in multiple inflammatory diseases, including endometritis. However, it remains unclear whether PGE2 is associated with pathogen-induced inflammatory damage to the endometrium. To clarify the role of PGE2 in pathogen-induced inflammatory damage, this study evaluated the production of PGE2, inflammatory factors, and damage-associated molecular patterns (DAMPs) in cultured Escherichia coli-infected bovine endometrial tissue. PGE2 production was significantly higher in E. coli-infected tissue, and in E. coli-infected tissue treated with 15-prostaglandin dehydrogenase (15-PGDH) inhibitors, as compared to uninfected tissue. Phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) were also upregulated in E. coli-infected tissue, while concentrations of arachidonic acid (AA), leukotrienes, DAMPs, and other proinflammatory factors increased. The accumulation of PGE2 clearly damaged the cultured tissue. Treatment with the COX-2, mPGES-1, EP4, and protein kinase A (PKA) inhibitors decreased the production of PGE2, inflammatory factors, and DAMPs, simultaneously alleviating the E. coli-induced endometrial tissue damage. Therefore, the PGE2 that was generated by COX-2 and mPGES-1 accumulated, and this pathogenic PGE2 increased inflammatory damage by upregulating inflammatory factors and DAMPs in E. coli-infected bovine endometrial tissue. This upregulation of inflammatory factors and DAMPs might be regulated by the EP4-PKA signaling pathway. Summary Sentence Escherichia coli infection of the bovine uterine explants activated the COX2-mPGES-PGE2 pathway, leading to the accumulation of PGE2, which induced proinflammatory cytokines IL-beta, IL-6, IL-8, TNF-alpha expression and tissue injure via PGE2-EP4-PKA pathway.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is closely associated with mitochondrial damage, diminished glutathione peroxidase 4 activity, dysfunction of the System Xc − cystine/glutamate antiporter, and disruptions in iron metabolism. Infections of the human reproductive system and associated reproductive disorders pose a significant global public health challenge, characterized by diverse pathogens and complex pathogenic mechanisms. Recent research has revealed that ferroptosis plays a critical role in the pathological processes of many of these infections. This review systematically elaborates on the central mechanistic role of ferroptosis in various pathologies of the reproductive system. These include CD4 + T cell depletion and immunological non-response in Human Immunodeficiency Virus (HIV) infection, the development of Human Papillomavirus (HPV)-associated cervical cancer, Staphylococcus aureus -induced endometritis and mastitis, as well as male infertility, pre-eclampsia, and ovarian cancer linked to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Despite the diversity of the pathogens, they can all trigger ferroptosis through common mechanisms, such as disrupting the Nrf2/GPX4 antioxidant axis, impairing the System Xc − –GSH–GPX4 pathway, and inducing dysregulation of iron metabolism. Furthermore, ferroptosis interacts intricately with pyroptosis and apoptosis, forming a complex network that collectively regulates the outcome of infections and the extent of tissue damage. Notably, ferroptosis plays a context-dependent dual role in various reproductive system infections. During the initial phases of infection, it exerts a protective effect by eliminating pathogens and curbing infection progression. In contrast, during advanced or chronic stages, ferroptosis exacerbates tissue injury and promotes disease pathogenesis. The ferroptosis pathway holds great therapeutic promise, either through inhibitors that safeguard host cells or inducers that eradicate drug-resistant bacteria by triggering a “ferroptosis-like” state. Nevertheless, challenges remain for clinical translation, as the ferroptosis network is incompletely understood, and the tissue selectivity and long-term safety of targeted drugs are unverified. Future studies must elucidate host-pathogen interactions to develop precise targeted therapies.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells’ mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients’ serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman’s rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments.

A healthy female genital tract harbors a microbiome dominated by lactic acid and hydrogen peroxide producing bacteria, which provide protection against infections by maintaining a low pH. Changes in the bacterial compositions of the vaginal microbiome can lead to bacterial vaginosis (BV), which is often associated with vaginal inflammation. Bacterial vaginosis increases the risk of acquiring sexually transmitted infections (STIs) like human immunodeficiency virus (HIV) and affects women’s reproductive health negatively. In pregnant women, BV can lead to chorioamnionitis and adverse pregnancy outcomes, including preterm premature rupture of the membranes and preterm birth. In order to manage BV effectively, good diagnostic procedures are required. Traditionally clinical and microscopic methods have been used to diagnose BV; however, these methods require skilled staff and time and suffer from reduced sensitivity and specificity. New diagnostics, including highly sensitive and specific point-of-care (POC) tests, treatment modalities and vaccines can be developed based on the identification of biomarkers from the growing pool of vaginal microbiome and vaginal metabolome data. In this review the current and future diagnostic avenues will be discussed.

The human microbiome functions as an intricate and coordinated microbial network, residing throughout the mucosal surfaces of the skin, oral cavity, gastrointestinal tract, respiratory tract, and reproductive system. The oral microbiome encompasses a highly diverse microbiota, consisting of over 700 microorganisms, including bacteria, fungi, and viruses. As our understanding of the relationship between the oral microbiome and human health has evolved, we have identified a diverse array of oral and systemic diseases associated with this microbial community, including but not limited to caries, periodontal diseases, oral cancer, colorectal cancer, pancreatic cancer, and inflammatory bowel syndrome. The potential predictive relationship between the oral microbiota and these human diseases suggests that the oral cavity is an ideal site for disease diagnosis and development of rapid point-of-care tests. The oral cavity is easily accessible with a non-invasive collection of biological samples. We can envision a future where early life salivary diagnostic tools will be used to predict and prevent future disease via analyzing and shaping the infant’s oral microbiome. In this review, we present evidence for the establishment of the oral microbiome during early childhood, the capability of using childhood oral microbiome to predict future oral and systemic diseases, and the limitations of the current evidence.

There is increasing evidence that the composition of a woman's vaginal microbiota significantly influences her sexual and reproductive health, including her risk of miscarriage, preterm birth, HIV and other sexually transmitted infections. Efforts to modulate the vaginal microbiota using antibiotic or probiotic therapy have shown limited lasting or reliable success. To explore the natural dynamics and causal pathways responsible for heterogeneity of vaginal microbiota composition we review the existing literature on its determinants, from the perspective of microorganism- and host-related factors. We then discuss how molecular approaches can be harnessed to advance our understanding of individual and population-level vaginal microbiota composition patterns. Work has been done to investigate determinants of microbial composition patterns in other body niches, but very little in the female genital tract so far. There is an urgent need to better understand vaginal microbiota composition patterns, across the lifespan, outside of the context of sexual health clinics, and in Sub-Saharan African women in whom vaginal microbiota composition may be a risk factor for HIV acquisition. More work is needed to clarify causal relationships between clinical symptoms, host genetic, host behavior, and molecular vaginal microbiota profiles. These insights will lay the groundwork for novel and targeted interventional approaches to improve women's sexual and reproductive health.

( ) is a Gram-negative obligate intracellular bacterium that causes reproductive tract complications in women, including ectopic pregnancies and tubal factor infertility. We hypothesized that mast cells, which are common at mucosal barriers, may contribute to responses to infection and aimed to define human mast cell responses to . Human cord blood-derived mast cells (CBMCs) were exposed to to assess bacterial uptake, mast cell degranulation, gene expression, and production of inflammatory mediators. The role of formyl peptide receptors and Toll-like receptor 2 (TLR2) were investigated using pharmacological inhibitors and soluble TLR2. Mast cell-deficient mice and littermate controls were used to examine the role of mast cells in influencing the immune response to infection in the female reproductive tract. bacteria were taken up by human mast cells but did not replicate efficiently inside CBMCs. -activated mast cells did not degranulate but maintained viability and exhibited cellular activation with homotypic aggregation and upregulation of ICAM-1. However, they significantly enhanced the gene expression of , , , , and . Inflammatory mediators were produced, including TNF, IL-1β, IL-1RA, IL-6, GM-CSF, IL-23, CCL3, CCL5, and CXCL8. Endocytic blockade resulted in reduced gene expression of , , and , suggesting induced mast cell activation in both extracellular and intracellular locations. The IL-6 response to was reduced when CBMCs were treated with coated with soluble TLR2. Mast cells derived from TLR2-deficient mice also demonstrated a reduced IL-6 response to . Five days following infection, mast cell-deficient mice showed attenuated CXCL2 production and significantly reduced numbers of neutrophils, eosinophils, and B cells in the reproductive tract when compared with mast cell-containing littermates. Taken together, these data demonstrate that mast cells are reactive to spp. through multiple mechanisms that include TLR2-dependent pathways. Mast cells also play an important role in shaping immune responses in reproductive tract infection through both effector cell recruitment and modification of the chemokine microenvironment.