{"title":"SQSTM1/p62 drives radiosensitivity in cervical cancer via autophagy-independent mechanisms","authors":"Mihoko Yoshida , Haruka Nunomura , Atsushi Furuta , Kiyotaka Yamada , Ippei Yasuda , Kyoko Takemura , Sayaka Tsuda , Akemi Yamaki-Ushijima , Tomoko Shima , Ryohei Ogawa , Qing-Li Zhao , Jun-Ichi Saitoh , Koki Saito , Eiji Morita , Mitsuaki Okodo , Akitoshi Nakashima","doi":"10.1016/j.jri.2025.104633","DOIUrl":"10.1016/j.jri.2025.104633","url":null,"abstract":"<div><div>Cervical cancer comprises squamous cell carcinomas (SCCs), which are generally radiosensitive; meanwhile, adenocarcinomas respond poorly to radiation. Here, we explored the role of selective autophagy receptors in modulating radiosensitivity across these subtypes. We found that SQSTM1/p62 was highly expressed in human papillomavirus (HPV)-positive SCC cell lines (HeLa, ME180) and clinical SCC specimens, but was low or undetectable in HPV-negative adenocarcinomas and the C33A cell line. Clonogenic assays confirmed that HPV-positive cells exhibited greater radiosensitivity than C33A. Upon irradiation, only HPV-positive cells showed upregulation of p62 and DNA-damage response proteins, whereas C33A cells did not. Treatment with autophagy inhibitors (bafilomycin A1 and chloroquine) further increased p62 levels in HPV-positive cells but not in HPV-negative cells. The sustained low p62 levels in C33A cells, regardless of autophagy inhibition, may represent a distinctive biomolecular feature of HPV-negative cervical cancer. Notably, overexpression of Atg4B to block autophagic flux without affecting p62 expression had no impact on radiosensitivity in either cell type, whereas pharmacologic inhibition of autophagy selectively enhanced radiation-induced cytotoxicity in HPV-positive cells. Conversely, siRNA-mediated knockdown of p62 in HPV-positive cells attenuated radiation-induced growth suppression. Together, these data indicate that p62 promotes radiosensitivity in HPV-positive cervical cancer through a mechanism distinct from classical autophagy. Therefore, p62 represents both a predictive biomarker for radiation response and a potential target for radiosensitization strategies in HPV-positive tumors, while its unresponsiveness in HPV-negative cancers suggests the need for alternative approaches in that context.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"171 ","pages":"Article 104633"},"PeriodicalIF":2.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886949","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}
Zeynep Toker Dincer , Muhammed Bahaddin Ates , Ayten Dag , Ilayda Turkoglu , Serdal Ugurlu
{"title":"Effects of anti-TNF agents on fertilization and pregnancy outcomes from a paternal perspective","authors":"Zeynep Toker Dincer , Muhammed Bahaddin Ates , Ayten Dag , Ilayda Turkoglu , Serdal Ugurlu","doi":"10.1016/j.jri.2025.104631","DOIUrl":"10.1016/j.jri.2025.104631","url":null,"abstract":"<div><div>Anti-TNF drugs are effective in the treatment of inflammatory arthritis. However, concerns about the impact of anti-TNF therapy on fertility, particularly in male patients, have been insufficiently explored. This study aimed to investigate the effects of anti-TNFs on male fertility and examine the pregnancy outcomes of their partners. This study was conducted on male patients with inflammatory arthritis undergoing anti-TNF therapy. Male patients whose female partners became pregnant during the anti-TNF therapy were evaluated regarding their partners' pregnancy outcomes. The characteristics of infertile patients were also analyzed. Additional evaluations included patient age, disease duration, anti-TNF treatment duration, as well as partners' comorbid conditions and the pregnancy outcomes of their partners prior to the initiation of anti-TNF therapy. A total of 101 male patients were included in the study. Of the total cohort, 70 male patients (69.3 %) did not desire children and were using contraception. The female partners of 27 male patients successfully conceived while their partners were receiving anti-TNF therapy. The remaining 4 couples were considered infertile. There were 52 pregnancies in total. Of these, 36 resulted in term births, 1 in a preterm birth, 1 in a stillbirth, 4 in elective abortions, and 10 in spontaneous abortions. Among the 27 female partners who conceived during anti-TNF therapy, 11 had also experienced pregnancies prior to the initiation of treatment. There were no statistically significant differences between the two periods in either the number of pregnancies or pregnancy outcomes. Anti-TNF therapy appears to be safe in terms of both fertility and pregnancy outcomes, although further investigations are warranted to better clarify its impact on male reproductive health.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"171 ","pages":"Article 104631"},"PeriodicalIF":2.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840844","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":"Association of elevated ACSL4 expression with impaired endometrial receptivity in endometriosis and restoration by ACSL4 inhibitor PRGL493","authors":"Lei Xu , Hong Wei , YuHong Shang , Qing Yang","doi":"10.1016/j.jri.2025.104630","DOIUrl":"10.1016/j.jri.2025.104630","url":null,"abstract":"<div><div>This study investigated the role of ACSL4 in endometrial receptivity disorders in endometriosis (EMs) and evaluated PRGL493, an ACSL4 inhibitor, as a potential therapeutic target. Bioinformatic analysis identified ACSL4 as a potential key regulator among ferroptosis and receptivity-related genes. Clinical samples from EMs patients showed significantly higher endometrial ACSL4 expression and lower receptivity marker expression (αVβ3, OPN, HOXA10) compared to controls. In a mouse EMs model, PRGL493 treatment reduced lesion volume, decreased lipid peroxidation, increased pinopode formation, and improved expression of receptivity markers. Similarly, in human endometrial organoids from EMs patients, PRGL493 ameliorated ultrastructural abnormalities, including mitochondrial condensation, decreased secretory granules, and endoplasmic reticulum expansion, and restored receptivity marker expression to levels comparable to the control. These findings demonstrate that ACSL4 overexpression is associated with endometrial receptivity disorders in EMs and that ACSL4 overexpression is a key pathological feature linked to endometrial receptivity impairment in EMs. Targeting ACSL4 with PRGL493 ameliorates receptivity defects, suggesting its therapeutic potential for EMs-associated infertility.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"171 ","pages":"Article 104630"},"PeriodicalIF":2.9,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773216","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}
Xuezi Tian , Juliette Krop , Marieke IJsselsteijn , Hanneke Kapsenberg , Jacqueline Anholts , Lotte van der Meeren , Leon Mei , Carin van der Keur , Dave Roelen , Lisa Lashley , Els van Beelen , Frits Koning , Marie-Louise van der Hoorn , Michael Eikmans
{"title":"Myeloid Cell – T Cell Interactions are Prominent in Pregnancies with Extreme Fetal-Maternal HLA Incompatibility and an Immune Tolerant Microenvironment","authors":"Xuezi Tian , Juliette Krop , Marieke IJsselsteijn , Hanneke Kapsenberg , Jacqueline Anholts , Lotte van der Meeren , Leon Mei , Carin van der Keur , Dave Roelen , Lisa Lashley , Els van Beelen , Frits Koning , Marie-Louise van der Hoorn , Michael Eikmans","doi":"10.1016/j.jri.2025.104558","DOIUrl":"10.1016/j.jri.2025.104558","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"170 ","pages":"Article 104558"},"PeriodicalIF":2.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713610","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}
Mariagiulia Spazzapan , Silvia Pegoraro , Roman Vuerich , Elena Longo , Lorella Pascolo , Gabriella Zito , Federico Romano , Luca Spazzapan , Andrea Romano , Giovanni Papa , Marie Pierre Piccinni , Serena Zacchigna , Giuseppe Ricci , Chiara Agostinis , Roberta Bulla
{"title":"Enhancing revascularization in Ovarian Tissue Transplantation (OTT): do bioengineering strategies improve functionality?","authors":"Mariagiulia Spazzapan , Silvia Pegoraro , Roman Vuerich , Elena Longo , Lorella Pascolo , Gabriella Zito , Federico Romano , Luca Spazzapan , Andrea Romano , Giovanni Papa , Marie Pierre Piccinni , Serena Zacchigna , Giuseppe Ricci , Chiara Agostinis , Roberta Bulla","doi":"10.1016/j.jri.2025.104577","DOIUrl":"10.1016/j.jri.2025.104577","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"170 ","pages":"Article 104577"},"PeriodicalIF":2.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713711","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":"Molecular Mechanisms of SIRT1 in Regulating Decidual Senescence and Decidualization in PCOS through Deacetylation Modification","authors":"Su Liu, Yingtan Zhuang, Ling Hong","doi":"10.1016/j.jri.2025.104564","DOIUrl":"10.1016/j.jri.2025.104564","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"170 ","pages":"Article 104564"},"PeriodicalIF":2.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714174","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}