{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:57:43Z","timestamp":1789790263921,"version":"4.0.1"},"reference-count":62,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Micro-\/nanoplastics (MNPs) and their associated endocrine-disrupting chemicals (EDCs) have emerged as pervasive environmental pollutants, with growing concern for their impact on male reproductive health. In this review, we synthesize the findings from twenty-one peer-reviewed studies published between January 2019 and March 2025, selected through a structured literature search conducted in accordance with the SANRA guidelines. Emphasis was placed on studies examining the cellular effects of MNPs and EDCs on Germ, Leydig, and Sertoli cells. The literature indicates multiple mechanisms of testicular toxicity, including degradation of the blood testis barrier, disruption of signaling pathways critical for spermatogenesis and hormone synthesis, induction of oxidative stress and inflammation, and structural and genetic damage to testicular tissues. These data, primarily derived from in vitro and animal models, not only highlight significant biological disruptions but also underscore the limitations in extrapolating results to human physiology. Differences in exposure routes, dosages, and species-specific responses present challenges to direct translation to humans. This review concludes that further human-centric research that mimics real-life exposure and impacts is essential to assess chronic, low-dose exposures and bridge the gap between experimental data and real-world reproductive outcomes, ultimately informing public health strategies and guiding future investigations into the reproductive risks posed by MNPs and EDCs.<\/jats:p>","DOI":"10.3390\/ijms262311457","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:56:41Z","timestamp":1764172601000},"page":"11457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Threat of Micro-\/Nanoplastics to Male Fertility: A Review of the Data and the Importance of Future Research"],"prefix":"10.3390","volume":"26","author":[{"given":"Shawn Aji","family":"Alex","sequence":"first","affiliation":[{"name":"Paul L. Foster School of Medicine, Texas Tech University Health Science Center at El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevin K.","family":"George","sequence":"additional","affiliation":[{"name":"Paul L. Foster School of Medicine, Texas Tech University Health Science Center at El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Guardiola","sequence":"additional","affiliation":[{"name":"Paul L. Foster School of Medicine, Texas Tech University Health Science Center at El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Clegg","sequence":"additional","affiliation":[{"name":"Paul L. Foster School of Medicine, Texas Tech University Health Science Center at El Paso, El Paso, TX 79905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","unstructured":"Ritchie, H., Roser, M., and Mispy, J. (2025, October 03). Plastic Production and Waste. Our World in Data. Available online: https:\/\/ourworldindata.org\/plastic-pollution."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1126\/science.aaz5819","article-title":"Plastic Rain in Protected Areas of the United States","volume":"368","author":"Brahney","year":"2020","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Amobonye, A., Bhagwat, P., Raveendran, S., Singh, S., and Pillai, S. (2021). Environmental impacts of microplastics and nanoplastics: A current overview. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.768297"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"168946","DOI":"10.1016\/j.scitotenv.2023.168946","article-title":"The potential toxicity of microplastics on human health","volume":"912","author":"Zhao","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"166258","DOI":"10.1016\/j.scitotenv.2023.166258","article-title":"Adverse effects of microplastics and nanoplastics on the reproductive system: A comprehensive review of fertility and potential harmful interactions","volume":"903","author":"Hong","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Maradonna, F., Vandenberg, L.N., and Meccariello, R. (2022). Editorial: Endocrine-disrupting compounds in plastics and their effects on reproduction, fertility, and development. Front. Toxicol., 4.","DOI":"10.3389\/ftox.2022.886628"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116519","DOI":"10.1016\/j.watres.2020.116519","article-title":"Drinking plastics? Quantification and qualification of microplastics in drinking water distribution systems by \u00b5FTIR and Py-GCMS","volume":"188","author":"Gomiero","year":"2021","journal-title":"Water Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.envpol.2017.11.043","article-title":"Airborne microplastics: Consequences to human health?","volume":"234","author":"Prata","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s13197-023-05720-4","article-title":"How microplastics interact with the food chain: A short overview of fate and impacts","volume":"61","author":"Saeedi","year":"2023","journal-title":"J. Food Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2024020","DOI":"10.5620\/eaht.2024020","article-title":"Health effects of microplastics and nanoplastics: Review of published case reports","volume":"39","author":"Otorkpa","year":"2024","journal-title":"Environ. Anal. Health Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.semcdb.2016.03.024","article-title":"Effect of environmental contaminants on spermatogenesis","volume":"59","author":"Jenardhanan","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ge, Z.J., Gioia Klinger, F., and Taketo, T. (2022). Editorial: Intra- and extra-environment and reproduction. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1020470"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility: Definition and epidemiology","volume":"62","author":"Wyns","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/humrep\/15.2.366","article-title":"High frequency of sub-optimal semen quality in an unselected population of young men","volume":"15","author":"Andersen","year":"2000","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chimento, A., Sirianni, R., Casaburi, I., and Pezzi, V. (2014). Role of estrogen receptors and G protein-coupled estrogen receptor in regulation of hypothalamus\u2013pituitary\u2013testis axis and spermatogenesis. Front. Endocrinol., 5.","DOI":"10.3389\/fendo.2014.00001"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1142\/S2661318223740833","article-title":"Cell-cell interactions in the testis that support male fertility","volume":"5","year":"2023","journal-title":"Fertil. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Goodman, H.M. (2009). Hormonal control of reproduction in the male. Basic Medical Endocrinology, Academic Press.","DOI":"10.1016\/B978-0-12-373975-9.00012-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mce.2017.12.013","article-title":"Recent progress in understanding the mechanisms of Leydig cell differentiation","volume":"468","author":"Inoue","year":"2018","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1210\/er.2014-1101","article-title":"The mammalian blood-testis barrier: Its biology and regulation","volume":"36","author":"Mruk","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Contino, M., Ferruggia, G., Indelicato, S., Pecoraro, R., Scalisi, E.M., Bracchitta, G., Dragotto, J., Salvaggio, A., and Brundo, M.V. (2023). In vitro nano-polystyrene toxicity: Metabolic dysfunctions and cytoprotective responses of human spermatozoa. Biology, 12.","DOI":"10.3390\/biology12040624"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1007\/s00018-004-4464-6","article-title":"Hsp70 chaperones: Cellular functions and molecular mechanism","volume":"62","author":"Mayer","year":"2005","journal-title":"Cell Mol. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1080\/13880209.2023.2168705","article-title":"Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics","volume":"61","author":"Zhang","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107220","DOI":"10.1016\/j.envint.2022.107220","article-title":"Repression of autophagy leads to acrosome biogenesis disruption caused by a sub-chronic oral administration of polystyrene nanoparticles","volume":"163","author":"Zhou","year":"2022","journal-title":"Environ. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"124028","DOI":"10.1016\/j.jhazmat.2020.124028","article-title":"Reproductive toxicity of polystyrene microplastics: In vivo experimental study on testicular toxicity in mice","volume":"405","author":"Hou","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114030","DOI":"10.1016\/j.ecoenv.2022.114030","article-title":"Microplastics from agricultural plastic mulch films: A mini-review of their impacts on the animal reproductive system","volume":"244","author":"Yuan","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110133","DOI":"10.1016\/j.ecoenv.2019.110133","article-title":"Exposure to polystyrene microplastics causes reproductive toxicity through oxidative stress and activation of the p38 MAPK signaling pathway","volume":"190","author":"Xie","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112803","DOI":"10.1016\/j.fct.2021.112803","article-title":"Maternal exposure to polystyrene nanoplastics during gestation and lactation induces hepatic and testicular toxicity in male mouse offspring","volume":"160","author":"Huang","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131470","DOI":"10.1016\/j.jhazmat.2023.131470","article-title":"Oral exposure to polystyrene nanoplastics reduced male fertility and even caused male infertility by inducing testicular and sperm toxicities in mice","volume":"454","author":"Xu","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15593258211019882","DOI":"10.1177\/15593258211019882","article-title":"Dose-dependent effect of polystyrene microplastics on the testicular tissues of the male Sprague Dawley rats","volume":"19","author":"Ijaz","year":"2021","journal-title":"Dose-Response"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115618","DOI":"10.1016\/j.ecoenv.2023.115618","article-title":"The male reproductive toxicity after nanoplastics and microplastics exposure: Sperm quality and changes of different cells in testis","volume":"267","author":"Gao","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12989-022-00453-2","article-title":"Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR\/cAMP\/PKA\/StAR pathway","volume":"19","author":"Jin","year":"2022","journal-title":"Part. Fibre Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"124543","DOI":"10.1016\/j.envpol.2024.124543","article-title":"Chronic exposure to polystyrene microplastics induced LHR reduction and decreased testosterone levels through NF-\u03baB pathway","volume":"358","author":"Jin","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113634","DOI":"10.1016\/j.fct.2023.113634","article-title":"Polystyrene nanoplastics inhibit StAR expression by activating HIF-1\u03b1 via ERK1\/2 MAPK and AKT pathways in TM3 Leydig cells and testicular tissues of mice","volume":"173","author":"Sui","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","first-page":"115907","article-title":"Polystyrene microplastics-induced oxidative stress and inflammatory response result in testicular dysfunction in male rats","volume":"272","author":"Sun","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"174536","DOI":"10.1016\/j.scitotenv.2024.174536","article-title":"Polystyrene microplastics trigger testosterone decline via GPX1","volume":"947","author":"Qu","year":"2024","journal-title":"Sci. Total. Environ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"116202","DOI":"10.1016\/j.ecoenv.2024.116202","article-title":"Polystyrene microplastics impair the functions of cultured mouse Leydig (TM3) and Sertoli (TM4) cells by inducing mitochondrial-endoplasmic reticulum damage","volume":"274","author":"Grillo","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114332","DOI":"10.1016\/j.ecoenv.2022.114332","article-title":"Polystyrene nanoplastics promote CHIP-mediated degradation of tight junction proteins by activating IRE1\u03b1\/XBP1s pathway in mouse Sertoli cells","volume":"248","author":"Hu","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12989-023-00546-6","article-title":"Long-term exposure to polystyrene microplastics triggers premature testicular aging via Ca2+\/ROS\/NF-\u03baB signaling in mouse Sertoli cells","volume":"20","author":"Wu","year":"2023","journal-title":"Part. Fibre Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e259","DOI":"10.3346\/jkms.2024.39.e259","article-title":"Examining the Relationship Between Polystyrene Microplastics and Male Fertility: Insights From an In Vivo Study and In Vitro Sertoli Cell Culture","volume":"39","author":"Jeon","year":"2024","journal-title":"J. Korean Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Han, Y., and Jin, X. (2025). The impact, mechanisms, and prevention strategies of environmental endocrine disruptors on male reproductive health. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1573526"},{"key":"ref_41","first-page":"1646","article-title":"Long-term field measurement of sorption of organic contaminants to five types of plastic pellets: Implications for plastic marine debris","volume":"47","author":"Rochman","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"123190","DOI":"10.1016\/j.envpol.2023.123190","article-title":"Microplastics as carriers of toxic pollutants: Source, transport, and toxicological effects","volume":"343","author":"Rafa","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e39426","DOI":"10.1016\/j.heliyon.2024.e39426","article-title":"Coexposure to microplastic and Bisphenol A exhacerbates damage to human kidney proximal tubular cells","volume":"10","author":"Verzola","year":"2024","journal-title":"Heliyon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jsbmb.2011.05.002","article-title":"Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects","volume":"127","author":"Rubin","year":"2011","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1365-2605.2005.00563.x","article-title":"Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters","volume":"29","author":"Foster","year":"2006","journal-title":"Int. J. Androl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1073\/pnas.0909519107","article-title":"Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)","volume":"107","author":"Hayes","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.1108190","article-title":"Epigenetic transgenerational actions of endocrine disruptors and male fertility","volume":"308","author":"Anway","year":"2005","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R109","DOI":"10.1530\/JOE-17-0023","article-title":"Exposure to endocrine disruptors during adulthood: Consequences for female fertility","volume":"233","author":"Rattan","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/toxsci\/kfae060","article-title":"Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis","volume":"200","author":"Hu","year":"2024","journal-title":"Toxicol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lehle, J.D., Lin, Y.H., Gomez, A., Chavez, L., and McCarrey, J.R. (2024). Endocrine disruptor-induced epimutagenesis in vit48ro: Insight into molecular mechanisms. bioRxiv, bioRxiv:2024.01.05.574355.","DOI":"10.7554\/eLife.93975.1"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"112040","DOI":"10.1016\/j.envres.2021.112040","article-title":"Effects of endocrine disrupting chemicals on gonad development: Mechanistic insights from fish and mammals","volume":"204 Pt B","author":"Delbes","year":"2022","journal-title":"Environ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"124644","DOI":"10.1016\/j.jhazmat.2020.124644","article-title":"Enhanced reproductive toxicities induced by phthalates contaminated microplastics in male mice (Mus musculus)","volume":"406","author":"Deng","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"165922","DOI":"10.1016\/j.scitotenv.2023.165922","article-title":"Raman Microspectroscopy evidence of microplastics in human semen","volume":"901","author":"Montano","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"173522","DOI":"10.1016\/j.scitotenv.2024.173522","article-title":"Prevalence and implications of microplastic contaminants in general human seminal fluid: A Raman spectroscopic study","volume":"937","author":"Li","year":"2024","journal-title":"Sci. Total. Environ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"162713","DOI":"10.1016\/j.scitotenv.2023.162713","article-title":"Detection and characterization of microplastics in the human testis and semen","volume":"877","author":"Zhao","year":"2023","journal-title":"Sci. Total. Environ."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, Y., Ling, W., Yang, J., and Xing, Y. (2025). Risk assessment of microplastics in humans: Distribution, exposure, and toxicological effects. Polymers, 17.","DOI":"10.3390\/polym17121699"},{"key":"ref_57","unstructured":"Savchuk, K. (2025, November 08). Microplastics and Our Health: What the Science Says. Stanford Medicine News Center. Available online: https:\/\/med.stanford.edu\/news\/insights\/2025\/01\/microplastics-in-body-polluted-tiny-plastic-fragments.html."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s10311-024-01727-1","article-title":"Health risk of human exposure to microplastics: A review","volume":"22","author":"Tang","year":"2024","journal-title":"Environ. Chem. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/envhealth.3c00052","article-title":"Potential health impact of microplastics: A review of environmental distribution, human exposure, and toxic effects","volume":"1","author":"Li","year":"2023","journal-title":"Environ. Health"},{"key":"ref_60","first-page":"179","article-title":"Potential role of environmental microplastics in male infertility","volume":"355","author":"Jiang","year":"2023","journal-title":"Toxicol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"De Falco, M., Favetta, L.A., Meccariello, R., Pogrmic-Majkic, K., and Svingen, T. (2024). Editorial: Endocrine disrupting chemicals in reproductive health, fertility, and early development. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1478655"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/toxsci\/kfaf108","article-title":"Systematic review of potential developmental and reproductive toxicity of microplastics","volume":"207","author":"Fitch","year":"2025","journal-title":"Toxicol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T05:14:21Z","timestamp":1764393261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":62,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311457"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311457","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}