Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980–2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the “metafor” package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35–3.75; I2: 44%), M. genitalium (OR: 2.04; CIL 1.18–3.53; I2: 20%), U. parvum (OR: 1.75; CI: 1.47–2.07; I2: 0%), U. urealyticum (OR: 1.50; CI: 1.08–2.07; I2: 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19–3.23; I2: 1%) or U. urealyticum (OR: 2.37; CI: 1.20–4.70; I2: 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42–3.08; I2: 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.

Objective: A homeostatic balance between reactive oxygen species production and the antioxidant redox system is an important component of normal pregnancy. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) preserves cellular homeostasis by enhancing the cell's innate antioxidant status to reduce oxidative stress and inflammatory damage to the cell during pregnancy. Active Nrf2, in the nucleus of the cell, transactivates various antioxidant genes. The objective of this systematic review was to synthesize evidence on the role of Nrf2 in various adverse pregnancy outcomes (APOs). Methods:We conducted a systematic review of the role of Nrf2 in pregnancy. Articles written in English, Portuguese, and Spanish were obtained from three different databases from inception until January 2021. The titles, abstracts and full text were reviewed independently by six reviewers. The quality of the included studies was assessed using a quality assessment tool developed to assess basic science and clinical studies. Nrf2 expression (gene and protein), functional contributions, and association with APOs were assessed.Results: A total of 747 citations were identified; 80 were retained for full review.Most studies on Nrf2 have been carried out using placental tissues and placentaderived cells. Limited studies have been conducted using fetal membranes, uterus, and cervix. Nuclear translocation of Nrf2 results in transactivation of antioxidant enzymes, including glutathione peroxidase, hemeoxygenase-1, and superoxide dismutase in gestational cells during pregnancy. This antioxidant response maintains cellular homeostasis during pregnancy. This promotes trophoblast cell survival and prevents cell death and abnormal angiogenesis in the placenta. Excessive and insufficient Nrf2 response may promote oxidative and reductive stress, respectively. This Nrf2 dysregulation has been associated with APOs including gestational diabetes mellitus, intrauterine growth restriction, reproductive toxicity, preeclampsia, and preterm birth. Conclusion:Several studies have localized and reported an association between Nrf2's differential expression in reproductive tissues and the pathogenesis of APOs. However, a comprehensive functional understanding of Nrf2 in reproductive tissues is still

IntroductionThe placenta is essential for fetal growth and survival and maintaining a successful pregnancy. The sterility of the placenta has been challenged recently; however, the presence of a placental microbiome has been controversial. We tested the hypothesis that the bacterial extracellular vesicles (BEVs) from Gram-negative bacteria as an alternate source of microbial DNA, regardless of the existence of a microbial community in the placenta.MethodsPlacentae from the term, not in labor Cesareans deliveries, were used for this study, and placental specimens were sampled randomly from the fetal side. We developed a protocol for the isolation of BEVs from human tissues and this is the first study to isolate the BEVs from human tissue and characterize them.ResultsThe median size of BEVs was 130–140 nm, and the mean concentration was 1.8–5.5 × 1010 BEVs/g of the wet placenta. BEVs are spherical and contain LPS and ompA. Western blots further confirmed ompA but not human EVs markers ALIX confirming the purity of preparations. Taxonomic abundance profiles showed BEV sequence reads above the levels of the negative controls (all reagent controls). In contrast, the sequence reads in the same placenta were substantially low, indicating nothing beyond contamination (low biomass). Alpha-diversity showed the number of detected genera was significantly higher in the BEVs than placenta, suggesting BEVs as a likely source of microbial DNA. Beta-diversity further showed significant overlap in the microbiome between BEV and the placenta, confirming that BEVs in the placenta are likely a source of microbial DNA in the placenta. Uptake studies localized BEVs in maternal (decidual) and placental cells (cytotrophoblast), confirming their ability to enter these cells. Lastly, BEVs significantly increased inflammatory cytokine production in THP-1 macrophages in a high-dose group but not in the placental or decidual cells.ConclusionWe conclude that the BEVs are normal constituents during pregnancy and likely reach the placenta through hematogenous spread from maternal body sites that harbor microbiome. Their presence may result in a low-grade localized inflammation to prime an antigen response in the placenta; however, insufficient to cause a fetal inflammatory response and adverse pregnancy events. This study suggests that BEVs can confound placental microbiome studies, but their low biomass in the placenta is unlikely to have any immunologic impact.

Aims To compare the cervicovaginal levels of human beta defensin (hBD)-1, 2 and 3 of women according to the status of Nugent-defined bacterial vaginosis (BV). Methods A total of 634 women of reproductive age were included in the study. Participants were equally distributed in two groups: according to the classification of vaginal smears according to Nugent criteria in normal (scores 0 to 3) and BV (scores ≥7). Cervicovaginal fluid samples were used for measurements of hBDs1, 2 and 3 levels by enzyme-linked immunosorbent assay (ELISA). Levels of each hBD were compared between the two study groups using Mann-Whitney test, with p-value <0.05 considered as significant. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for sociodemographic variables and hBD1-3 levels associated with BV a multivariable analysis. Correlation between Nugent score and measured levels of hBDs1-3 were calculated using Spearman’s test. Results Cervicovaginal fluids from women with BV showed lower levels of hBD-1 [median 2,400.00 pg/mL (0–27,800.00); p<0.0001], hBD-2 [5,600.00 pg/mL (0–45,800.00); p<0.0001] and hBD-3 [1,600.00 pg/mL (0–81,700.00); p = 0.012] when compared to optimal microbiota [hBD-1: [median 3,400.00 pg/mL (0–35,600.00), hBD-2: 12,300.00 pg/mL (0–95,300.00) and hBD-3: 3,000.00 pg/mL (0–64,300.00), respectively]. Multivariable analysis showed that lower levels of hBD-1 (OR: 2.05; 95% CI: 1.46–2.87), hBD-2 (OR: 1.85; 95% CI: 1.32–2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37–2.64) were independently associated BV. Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman’s rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman’s rho = -0.2117; p = 0.0001). Conclusions Bacterial vaginosis is associated with lower cervicovaginal levels of hBDs1-3 in reproductive-aged women.

Introdução: A infecção pelo papilomavirus humano entre as mulheres que fazem sexo com mulheres ainda é pouco conhecida e escassos estudos apoiam a transmissão sexual entre essa população. Objetivo: Descrever a prevalência e genotipagem de infecção pelo papilomavírus humano entre mulheres que fazem sexo com mulheres. Métodos: Estudo descritivo que incluiu 110 mulheres que declararam fazer sexo com mulheres nos últimos 12 meses, maiores de 18 anos e residentes no interior de São Paulo. Os dados foram obtidos por entrevista e exame físico ginecológico entre janeiro de 2019 e janeiro de 2020. Apesquisa e genotipagem para o papilomavírus humano foi realizada pelo Kit XGEN MULTI HPV CHIP, que possibilita a identificação de 35 genótipos, sendo os de alto risco (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73 e 82) e baixo risco (6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 67, 69, 70, 71, 72, 81 e 84). Os dados foram analisados por estatística descritiva. A pesquisa recebeu parecer favorável do comitê de ética local (parecer n. 3.009.410). Resultados: A maioria das participantes se autodeclarava branca (73,6%), não vivia com parceiras (86,4%), recebia penetração vaginal (92,7%) e fazia uso inconsistente de preservativo nas relações sexuais (89,1%). Aproximadamente um terço delas referiu troca de parcerias sexuais nos três meses que antecederam a coleta de dados (32,7%). A prevalência geral de papilomavírus humano foi de 56,4% e os genótipos de alto risco encontrados foram 16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 68, 73, 82, e de baixo risco 6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 67, 70, 71, 72, 81. Conclusão: mulheres que fazem sexo com mulheres possuem altas prevalências de papilomavírus humano, com destaque para os genótipos de alto risco encontrados, demonstrando sua vulnerabilidade aos agravos relacionados ao papilomavírus humano.