{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:47:59Z","timestamp":1776772079285,"version":"3.51.2"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"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":["Environmental Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Excessive pesticide exposure is increasingly associated with oxidative stress mediated reproductive toxicity. Pyriproxyfen (PPF), a widely used juvenile hormone analog insecticide, has been implicated in oxidative stress mediated reproductive toxicity. This study investigated the mechanisms underlying PPF\u2010induced testicular damage and evaluated the protective potential of\n                    <jats:italic>Ephedra pachyclada<\/jats:italic>\n                    extract (EPE), focusing on modulation of the Nrf2\/ARE and NF\u2010\u03baB pathways. Adult male rats were exposed to PPF (20\u2009mg\/kg body weight) with or without EPE administration (140\u2009mg\/kg body weight). Oxidative stress biomarkers, inflammatory mediators, steroidogenic gene expression, serum testosterone, sperm parameters, and histopathological alterations were assessed. LC\u2013MS analysis characterized the phytochemical composition of EPE. PPF exposure significantly increased lipid peroxidation and reduced antioxidant enzyme activities, accompanied by downregulation of Nrf2 and its downstream targets. In parallel, NF\u2010\u03baB expression and pro\u2010inflammatory cytokines were elevated. These molecular disturbances were associated with suppression of StAR, SR\u2010B1, CYP11A1, 3b\u2010HSD, and 17b\u2010HSD expression, decreased testosterone levels, reduced sperm count and motility, increased sperm abnormalities, and structural degeneration of seminiferous tubules. EPE administration markedly attenuated oxidative stress, restored Nrf2 signaling, suppressed inflammatory responses, normalized steroidogenic gene expression and testosterone levels, and improved sperm quality and testicular histology. LC\u2013MS profiling revealed a predominance of flavonol glycosides, flavone\n                    <jats:italic>C<\/jats:italic>\n                    \u2010glycosides, flavan\u20103\u2010ols, and biflavonoids. These findings suggest that EPE mitigates PPF\u2010induced reproductive toxicity through restoration of redox and inflammatory homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/tox.70107","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:09:01Z","timestamp":1776769741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects of\n                    <i>Ephedra pachyclada<\/i>\n                    Boiss. Extract Against Pyriproxyfen\u2010Induced Male Reproductive Toxicity: Modulation of Oxidative and Inflammatory Pathways"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-0030","authenticated-orcid":false,"given":"Mohamed","family":"Seif","sequence":"first","affiliation":[{"name":"Food Toxicology and Contaminants Department Food Industries and Nutrition Research Institute, National Research Centre  Dokki Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2862-2907","authenticated-orcid":false,"given":"Bin","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science Zhejiang University of Technology  Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science Zhejiang University of Technology  Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel\u2010Nasser A.","family":"Madboli","sequence":"additional","affiliation":[{"name":"Animal Reproduction and Artificial Insemination Department Veterinary Research Institute, National Research Centre  Dokki Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-1066","authenticated-orcid":false,"given":"Diaa A.","family":"Marrez","sequence":"additional","affiliation":[{"name":"Food Toxicology and Contaminants Department Food Industries and Nutrition Research Institute, National Research Centre  Dokki Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-7435","authenticated-orcid":false,"given":"Mahmoud","family":"Emam","sequence":"additional","affiliation":[{"name":"Phytochemistry and Plant Systematics Department National Research Centre  Dokki Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.62940\/als.v8i2.1094"},{"key":"e_1_2_13_3_1","first-page":"1","article-title":"Pesticide Exposures and Chronic Kidney Disease of Unknown Etiology: An Epidemiologic Review","volume":"16","author":"Valcke M.","year":"2017","journal-title":"Environmental Health"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1061934816050117"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3AY41742E"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jes.2021.08.047"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27228072"},{"key":"e_1_2_13_8_1","first-page":"188","article-title":"New HPLC and Fluorometric Methods for the Determination of Pyriproxyfen and Pyridalyl Insecticide Residues in Tomatoes","volume":"97","author":"Farouk M.","year":"2014","journal-title":"Journal of Analytical & Industrial Research"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/agronomy12081829"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-22129-2"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2016.1223014"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1584\/jpestics.R08-02"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2018.01.010"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2020.105448"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18126576"},{"key":"e_1_2_13_16_1","first-page":"43","article-title":"Infertility: Prevalence and Consequences","volume":"10","author":"Obeagu E. 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