Xufei Fan, Yali Yang, Xiaodan Zhu, Lichao Yuan, Min Hu, Xiaoxia Bai
{"title":"ERα Facilitates Hypoxia-induced Ferroptosis in Placental Trophoblasts by Transcriptionally Activating ACSL4.","authors":"Xufei Fan, Yali Yang, Xiaodan Zhu, Lichao Yuan, Min Hu, Xiaoxia Bai","doi":"10.1111/aji.70258","DOIUrl":"10.1111/aji.70258","url":null,"abstract":"<p><strong>Problem: </strong>Preeclampsia (PE), characterized by hypertension and proteinuria, involves placental dysfunction linked to oxidative stress and ferroptosis. The role of estrogen receptor α (ERα) in hypoxia-induced trophoblast ferroptosis remains unclear.</p><p><strong>Method of study: </strong>A PE rat model was established using L-NAME injection. Placental tissues were analyzed for protein expression via Western blot. In vitro, HTR-8/SVneo cells were cultured under hypoxic conditions to simulate PE-related hypoxia. ERα was knocked down using siRNAs, and acyl-CoA synthetase long-chain family member 4 (ACSL4) was overexpressed via plasmid transfection. Cell viability, apoptosis, migration, oxidative stress parameters, and ferroptosis-related indicators were assessed using CCK-8, flow cytometry, Transwell assays, and specific biochemical kits. In addition, primary syncytiotrophoblast (STB) cells were isolated from placentas of healthy and PE rats for validation experiments. The transcriptional regulation of ACSL4 by ERα was examined using dual luciferase reporter assays.</p><p><strong>Results: </strong>In PE rat placentas, ERα and ACSL4 were significantly upregulated, while GPX4 and SLC7A11 were downregulated. In addition, the lipid peroxidation products 4-HNE and MDA were significantly increased in PE placental tissues. Hypoxia induced ferroptosis in HTR-8/SVneo cells, characterized by increased Fe<sup>2</sup> <sup>+</sup> levels, elevated 4-HNE and MDA levels, lipid peroxidation, and activation of the ERα/ACSL4 axis. Knockdown of ERα attenuated hypoxia-induced cell injury, oxidative stress, and ferroptosis, whereas ACSL4 overexpression reversed these protective effects. Furthermore, experiments in primary STB cells isolated from PE rats showed that ERα knockdown similarly alleviated ferroptosis-associated injury and suppressed ACSL4 expression. Mechanistically, ERα bound directly to the ACSL4 promoter and transcriptionally activated its expression.</p><p><strong>Conclusions: </strong>The ERα-ACSL4 axis plays a critical role in hypoxia-induced ferroptosis in placental trophoblasts. ERα transcriptionally activates ACSL4, promoting lipid peroxidation and ferroptosis, thereby contributing to placental dysfunction in PE. These findings provide a novel theoretical basis for understanding PE pathogenesis and highlight potential therapeutic targets for intervention.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70258"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969682","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":"Effect of Recombinant Human Granulocyte Colony-Stimulating Factor on Pregnancy Outcomes in Patients With Recurrent Pregnancy Loss: A Single-Center Retrospective Study.","authors":"Luming Chen, Fangxiang Mu, Hui Yao, Fang Wang","doi":"10.1111/aji.70248","DOIUrl":"10.1111/aji.70248","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore how recombinant human granulocyte colony-stimulating factor (rhG-CSF) impacts pregnancy outcomes among patients with recurrent pregnancy loss (RPL), especially the effects of different rhG-CSF administration types on these outcomes.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 504 RPL patients treated at the Lanzhou University Second Hospital, including 291 in the treatment group (receiving rhG-CSF) and 213 in the control group. Potential confounding factors were adjusted by Propensity Score Matching (PSM) and Inverse Probability of Treatment Weighting (IPTW). Logistic regression was employed to assess the association between rhG-CSF and pregnancy outcomes. Additionally, exploratory subgroup analysis was performed based on different rhG-CSF administration types (short-acting, long-acting, and sequential therapy).</p><p><strong>Results: </strong>Overall, rhG-CSF treatment did not significantly improve the rates of live births (OR = 1.259, 95% CI: 0.771-2.062, p = 0.357), preterm births (OR = 1.095, 95% CI: 0.304-6.143, p = 0.917), or neonatal unit admissions (OR = 1.123, 95% CI: 0.205-7.511, p = 0.898). However, exploratory subgroup analysis revealed that short-acting rhG-CSF was linked to a lower live birth rate (LBR) (aOR = 0.476, 95% CI: 0.224-0.971), while sequential therapy significantly increased LBRs (aOR = 2.417, 95% CI: 1.384-4.268). Further analysis showed that there were no significant differences in the rates of preterm birth and neonatal unit admissions among different groups.</p><p><strong>Conclusion: </strong>Although rhG-CSF showed no significant overall benefit for pregnancy outcomes in RPL patients, exploratory subgroup analyses revealed divergent effects based on administration types. While a potential negative association was observed with short-acting rhG-CSF and a positive impact with sequential therapy, these subgroup-specific findings should be interpreted with caution and require validation in larger, dedicated prospective cohorts.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70248"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760071","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":"The 45<sup>th</sup> Annual Meeting of the American Society for Reproductive Immunology, May 24-28, Lexington, Kentucky.","authors":"","doi":"10.1111/aji.70242","DOIUrl":"https://doi.org/10.1111/aji.70242","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 Suppl 1 ","pages":"e70242"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980229","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":"A Bidirectional Survivin Promoter Enhances IL-2, GM-CSF, and Apoptin Co-expression for Breast Cancer Gene Therapy.","authors":"Omid Barzegari, Fatemeh Ghadimi, Fatemeh T Shamsabadi, Masoud Golalipour, Majid Shahbazi","doi":"10.1111/aji.70226","DOIUrl":"10.1111/aji.70226","url":null,"abstract":"<p><p>Breast cancer remains a significant global health challenge, necessitating the development of innovative therapeutic strategies. This study aims to integrate immunotherapy and suicide gene therapy for breast cancer treatment. The cytokines IL-2 and GM-CSF, which are crucial in orchestrating immune responses against cancer, are the focal points of investigation. This study focused on the co-expression of these cytokines alongside apoptin, a promising protein derived from chicken anemia virus, via the bidirectional survivin promoter (pAIG). The constructed vectors were transfected into MCF-7 cells, which resulted in a significant increase in gene expression. Compared with individual cytokine and apoptin vectors (pIG and pA), the pAIG vector exhibited superior efficacy, reducing cell viability and inducing apoptosis (31.7%) at 72 h post-transfection. Exploration of the interaction of apoptin revealed its association with the human PIK3R1 protein, which interacts with both cytokines, contributing to the inhibition of cell viability. Leveraging the survivin promoter for co-expression presents a promising avenue for targeted breast cancer gene therapy, potentially disrupting intricate signaling networks involved in cancer progression. This study provides valuable insights into the synergistic effects of IL-2, GM-CSF, and apoptin co-expression, offering a compelling approach to advancing breast cancer treatment. These findings contribute to the broader landscape of cancer gene therapy, emphasizing the potential of combining immunomodulatory agents and gene-directed approaches to improve therapeutic outcomes.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70226"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866263","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}
Naveen Kumar Sanku, Amit Singh Pawaia, Ranjana Roy, Hariharan Srinivasan
{"title":"Comment on \"Prognostic Value of Systemic Immune-Inflammation Index in Patients With Gynecological Tumors: A Systematic Review and Meta-Analysis\".","authors":"Naveen Kumar Sanku, Amit Singh Pawaia, Ranjana Roy, Hariharan Srinivasan","doi":"10.1111/aji.70247","DOIUrl":"https://doi.org/10.1111/aji.70247","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70247"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832513","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}