{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:10:08Z","timestamp":1789996208232,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The main functions of testes are sperm production and androgen secretion in testicular befitting microenvironment. Excessive level of the reactive oxygen species (ROS) from metabolism and cellular events can lead to oxidative stress (OS) and ferroptosis, which injure the functions of mitochondria and endoplasmic reticulum (ER) of testicular cells, leading to the impaired spermatogenesis and spermiogenesis, as well as insufficient androgen. Our previous studies have shown that peroxiredoxin 4 (Prdx4) is a vital ER\u2010located protector against endoplasmic reticulum stress (ERS) in ovarian granulosa cells. In this study, we explored whether Prdx4 played a beneficial role in testes, and the potential application value in male reproduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Prdx4 knockout mice and Prdx4\n                      <jats:sup>\u2212\/y<\/jats:sup>\n                      Leydig cells were established using CRISPR\/Cas9 system, the natural adult (9 weeks) mice, aging (9 months) mice, and wild\u2010type MLTC\u20101 cells were used as control. To further investigate the protective effect of Prdx4 in the adult mice, the testicular 43\u00b0C water\u2010bath was used to induce an OS model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The male Prdx4\n                      <jats:sup>\u2212\/y<\/jats:sup>\n                      mice aged over 9 months showed the age\u2010related pathology of seminiferous tubule, the increased OS and ERS, and the decreased fertility. The adult Prdx4\n                      <jats:sup>\u2212\/y<\/jats:sup>\n                      mice under heat stress manifested increased levels of OS, including almost 1.5\u2010fold rise in 4\u2010hydroxynonenal (4\u2010HNE) and 8\u2010hydroxy\u20102\u2032\u2010 deoxyguanosine (8\u2010OHdG), higher ferroptosis, and poorer fertility. Prdx4\n                      <jats:sup>\u2212\/y<\/jats:sup>\n                      Leydig cells showed a higher level of ferroptosis after hydrogen peroxide treatment. ACSL4 increased by 18.6% while COX2 increased by 13.5%, and the expressions of GPX4 and SLC7A11 decreased by 49.2% and 24.3%, respectively. Increased levels of ferroptosis in MLTC\u20101 leads to mitochondria\u2010derived OS and apoptosis, which can be partially restored by deferoxamine and overexpressing SLC7A11.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We concluded that Prdx4 as a protective factor plays a critical role in preserving spermatogenesis by alleviating testicular OS and ferroptosis, and that Prdx4 may be known as a potential target in mitigating the adverse effects of natural aging and OS injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70221","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T10:08:12Z","timestamp":1774606092000},"page":"2329-2346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peroxiredoxin 4 Involved in Spermatogenesis by Affecting Oxidative Stress and Ferroptosis"],"prefix":"10.1111","volume":"14","author":[{"given":"Shuning","family":"Yuan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nini","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Ma","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center Affiliated Maternity and Child Health Care Hospital of Nantong University  Nantong Jiangsu 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