Brittany Dodson, Talia Suner, Emilie L. Vander Haar, Yiping W. Han
{"title":"Oral Microbiome and Adverse Pregnancy Outcomes","authors":"Brittany Dodson, Talia Suner, Emilie L. Vander Haar, Yiping W. Han","doi":"10.1111/aji.70107","DOIUrl":"https://doi.org/10.1111/aji.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Intrauterine infection plays a pivotal role in adverse pregnancy outcomes including preterm birth, stillbirth, neonatal sepsis, and pregnancy-associated hypertension and diabetes. Development of culture-independent microbial detection technologies have greatly advanced our knowledge of microbes implicated in intrauterine infection. Increasing evidence demonstrates the involvement of oral bacteria, especially <i>Fusobacterium nucleatum</i>, in adverse pregnancy outcomes. This review summarizes the oral bacteria detected in intrauterine cavity, their route of dissemination and consequences, and the use of omega-3 fatty acids to suppress microbial-induced placental inflammation.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Special Issue on Preeclampsia and Beyond","authors":"Surendra Sharma, Nardhy Gomez-Lopez, George Saade","doi":"10.1111/aji.70103","DOIUrl":"https://doi.org/10.1111/aji.70103","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Addison W. Alley, Paweł Łaniewski, Gabrielle T. Bruno, Drew V. Moffitt, Gayatri Arani, Leslie V. Farland, Melissa M. Herbst-Kralovetz
{"title":"Vaginal Microbiome Dominated by Lactobacillus Positively Impacts Clinical Pregnancy in Patients With Frozen Embryo Transfers","authors":"Addison W. Alley, Paweł Łaniewski, Gabrielle T. Bruno, Drew V. Moffitt, Gayatri Arani, Leslie V. Farland, Melissa M. Herbst-Kralovetz","doi":"10.1111/aji.70108","DOIUrl":"https://doi.org/10.1111/aji.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>There is evidence that the bacterial microbiome of the female reproductive tract affects fertility outcomes, but the findings are conflicting, and studies are lacking in racially and ethnically diverse populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this prospective cohort study, vaginal swabs were collected from 87 female patients at time of frozen embryo transfer (FET) after oral estradiol preparation of the endometrium. The primary outcome was an ultrasound demonstrating a viable intrauterine pregnancy. 16s rRNA gene sequencing was performed on the swabs to compare the vaginal microbiome between those who achieved a viable pregnancy compared to those who did not.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 87 patients participated in the study, of whom 25% (22/87) reported a race other than White and 17% (15/87) identified as Hispanic. There were 55 patients who achieved clinical pregnancy. Patients who achieved pregnancy had a significantly higher prevalence of <i>Lactobacillus</i>-dominant profiles: 67% (37/55) compared with 41% (13/32) of the nonpregnant group (<i>p</i> = 0.024), with a relative risk of pregnancy of 1.52 [1.05, 2.20]. Nonpregnant patients exhibited more <i>Enterobacteriacae</i> and other opportunistic pathogens. Hispanic patients in the study cohort demonstrated decreased clinical pregnancy rates (<i>p</i> = 0.021) and lower <i>Lactobacillus</i> dominance (<i>p</i> = 0.01) compared to non-Hispanic White women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study suggests that a vaginal microbiome predominated by <i>Lactobacillus</i> is associated with successful embryo implantation and early establishment of pregnancy after FET. Decreased <i>Lactobacillus</i> dominance may contribute to reproductive outcome disparities among Hispanic women. These findings support the consideration of the female reproductive microbiome in the evaluation and treatment of infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Gut and Reproductive Tract Microbiota on Estrogen Metabolism in Endometriosis","authors":"ZeFeng Li, ZhaoFang Yin, WeiQi Chen, ZhiHong Wang","doi":"10.1111/aji.70109","DOIUrl":"https://doi.org/10.1111/aji.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The incidence of endometriosis is rising, particularly among younger populations, yet current diagnostic and therapeutic approaches remain limited. This highlights the urgent need for novel diagnostic tools and effective treatments. Recent studies have shown that intestinal and reproductive tract bacterial dysbiosis is closely associated with the development of endometriosis and plays a key role in the regulation of estrogen metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review aims to provide a comprehensive overview of the mechanisms of the microbiota's role in regulating estrogen levels and influencing the development and progression of endometriosis, providing important insights into the diagnosis and management of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Microbial changes not only promote estrogen imbalance by regulating β-glucuronidase activity, but also respond to estrogen imbalance by affecting the expression of metabolites such as short-chain fatty acids and lipopolysaccharides. In addition, significant fluctuations in estrogen levels also affect the composition of the microbial community. Both factors jointly lead to changes in the immune microenvironment of endometriosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madhuri Tatiparthy, Ananth Kumar Kammala, Rheanna Urrabaz-Garza, Tilu Jain Thomas, Souvik Paul, Jaganmoy Choudhury, Ramkumar Menon, Lauren S. Richardson
{"title":"The Impacts of TNF-α-Induced Inflammation on Amnion Epithelial Cells: Exploring Stem Cell Gene Expression, Senescence, Inflammatory Responses, and Cellular Transition","authors":"Madhuri Tatiparthy, Ananth Kumar Kammala, Rheanna Urrabaz-Garza, Tilu Jain Thomas, Souvik Paul, Jaganmoy Choudhury, Ramkumar Menon, Lauren S. Richardson","doi":"10.1111/aji.70106","DOIUrl":"https://doi.org/10.1111/aji.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is crucial to understand the relationship between inflammation and adverse pregnancy outcomes such as preterm birth and premature membrane rupture. Inflammation alters stem cell factors and cell transitions, disrupting immune balance and leading to adverse outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study explored the effects of the pro-inflammatory cytokine TNF-α on Amnion epithelial cells (AECs), focusing on stem cell transcription factors (TFs), senescence, and the epithelial-mesenchymal transition (EMT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptomic data were generated to compare the stem cell TFs expression (KLF4, c-MYC, OCT-4, SOX2, NANOG) between the placenta and fetal membrane (FM); AEC were treated with 50 ng/mL TNF-α for 48 h. Gene expression of stem cell TFs was assessed using qPCR; p38 MAPK activation and differential expression of KLF4, c-MYC were subsequently verified by Western blotting. Cellular senescence was evaluated using SA-β-Gal staining, and the pro-inflammatory cytokines IL-6 and IL-8 were measured using ELISA. The EMT was determined by measuring cell shape index and vimentin/CK-18 immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The placenta and the FM expressed higher mRNA levels of KLF4 than c-MYC, SOX2, OCT-4, and NANOG. AEC exhibited significantly higher KLF4 and c-MYC (<i>p</i> < 0.05). KLF4 downregulation (<i>p</i> < 0.05) and an increase in c-MYC (<i>p</i> < 0.01) in mRNA and protein levels were observed. The p38 MAPK activation (<i>p</i> < 0.01) increased cellular senescence (<i>p</i> < 0.05) and increased IL-6, IL-8 production (<i>p</i> < 0.01) with no change in cellular transition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows how TNF-α affects stem cell TFs and impacts cellular integrity, senescence, and inflammatory responses, thus influencing adverse pregnancy outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne Laskewitz, Lieske Wekema, Marijke M. Faas, Jelmer R. Prins
{"title":"Maternal Immune Characteristics at Mid and Late Pregnancy Are Mostly Independent of Fetal Allogeneity in Mice","authors":"Anne Laskewitz, Lieske Wekema, Marijke M. Faas, Jelmer R. Prins","doi":"10.1111/aji.70089","DOIUrl":"https://doi.org/10.1111/aji.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>During pregnancy, the maternal immune system undergoes different adaptations to establish tolerance toward the fetus. Several factors are known to affect maternal immune adaptations, including fetal allo-antigens. Although, the effects of fetal antigens have clearly been shown in early pregnancy, the influence of these antigens in mid- and late pregnancy are not fully known.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this study, we investigated the impact of fetal allo-antigens during pregnancy on maternal immune adaptations by comparing immunological changes in semi-allogeneic and syngeneic pregnancies in mice. Pregnant mice were analyzed at gestation day 10 (GD10) and gestation day 18 (GD18), and immune responses were assessed in the spleen, uterus draining para-aortic lymph nodes (PALN) and peripheral blood analyzing T cells, monocytes and their subsets. In addition, T cells were analyzed after stimulation using PMA or male antigens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analyses of memory T cells, Tregs and monocytes (and subsets) demonstrated that fetal semi-allogeneity only had a minor influence on the maternal immune parameters in mid and late gestation. Immune stimulation experiments, using either PMA or syngeneic or allogeneic paternal antigens, revealed minor differences in cytokine production between general immune stimulation and paternal specific stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results show that immune adaptations ad mid and late pregnancy are likely not mainly driven by fetal allo-antigens. This study contributes to a deeper understanding of the maternal immune system during pregnancy (either syngeneic or semi-allogeneic).</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcelo Borges Cavalcante, Conor Harrity, Thanh Luu, Joy Fatunbi, Koji Nakagawa, Yuan Zhang, Tao Zhang, Hallah Alanazi, Li Wu, Sungki Lee, Ricardo Barini, Joanne Kwak-Kim
{"title":"2025 American Society for Reproductive Immunology Guidelines for the Treatment of Recurrent Pregnancy Losses: Practice Recommendations From the ASRI Clinical Reproductive Immunology Fellowship","authors":"Marcelo Borges Cavalcante, Conor Harrity, Thanh Luu, Joy Fatunbi, Koji Nakagawa, Yuan Zhang, Tao Zhang, Hallah Alanazi, Li Wu, Sungki Lee, Ricardo Barini, Joanne Kwak-Kim","doi":"10.1111/aji.70099","DOIUrl":"https://doi.org/10.1111/aji.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>Various immunomodulatory treatments have been applied to women with recurrent pregnancy losses since a significant proportion of them have cellular and autoimmune abnormalities. However, immunomodulatory treatments are often considered controversial for their efficacies. Often, they are provided to unselected patients without investigating potential etiologies by healthcare providers without appropriate reproductive immunology training and qualifications. To eliminate these concerns, the American Society for Reproductive Immunology (ASRI) established the Clinical Reproductive Immunology Fellowship and has been certifying reproductive immunologists. The approach to RPL from a reproductive immunology perspective requires a detailed understanding of underlying immunopathology, advanced knowledge of clinical and basic science and translational research, and the capability to evaluate the available evidence. The immunotherapy guideline development group, composed of clinical reproductive immunology fellows, ASRI, reviewed the currently available data and developed the clinical guidelines for immunotherapy.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanah M. Georges, Abigail C. Fischer, Vikki M. Abrahams
{"title":"Intermediate Signaling Mechanisms Regulating Human Fetal Membrane Responses to Gram-Positive Bacterial Peptidoglycan","authors":"Hanah M. Georges, Abigail C. Fischer, Vikki M. Abrahams","doi":"10.1111/aji.70090","DOIUrl":"https://doi.org/10.1111/aji.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Chorioamnionitis and preterm birth are leading causes of neonatal morbidity and mortality. Despite ongoing research, the signaling pathways involved in the pathogenesis of chorioamnionitis—inflammation of the fetal membranes (FM)—are not well understood. Previously, we reported that FMs utilize miR-146a-3p as an endogenously produced danger signal to sequentially activate Toll-like receptor (TLR) 8 and subsequent inflammation following lipopolysaccharide stimulation of TLR4. In this current study, following stimulation of fetal membrane explants by the TLR2 agonist peptidoglycan (PDG), we investigated sequential microRNA-activation of TLR8, intermediate signaling pathways NFκB and MAPK (p38, ERK), and their effects on inflammation and mediators of membrane weakening.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Human FMs explants were treated with or without PDG in the presence or absence of inhibitors to TLR7, TLR8, p65 NFκB, p38 MAPK, or ERK. Culture supernatants were measured for secreted factors by ELISA, tissue RNA was measured for TLR7/8-activating miRs by RT-qPCR, and tissue protein was measured for phosphorylated proteins by Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PDG-treated FMs produced elevated levels of TLR8-activating miR-146a-3p in a p65 NFκB-dependent manner. PDG-treated FMs produced elevated levels of the pro-inflammatory cytokine IL-1β, the neutrophil recruiting chemokine IL-8, and membrane weakening MMP1, MMP9, and PGE<sub>2</sub> in a TLR8-dependent manner. Except for MMP9, this inflammatory and membrane weakening response to PDG was dependent upon p65 NFκB, p38 MAPK, and ERK signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study gives new insight into the molecular mechanisms involved in FM responses to Gram-positive bacteria and into the pathogenesis of chorioamnionitis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}