{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:01:12Z","timestamp":1790114472781,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Pharmacology and Toxicology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01ES032144"],"award-info":[{"award-number":["R01ES032144"]}]},{"name":"NIH","award":["R01ES035766"],"award-info":[{"award-number":["R01ES035766"]}]},{"award":["HT9425-23-1-0809"],"award-info":[{"award-number":["HT9425-23-1-0809"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse female reproductive outcomes. However, most prior studies examined individual PFAS, despite that humans are exposed to complex PFAS mixtures. Here, we investigated the ovarian effects of a mixture of five commonly detected long-chain PFAS, including PFOS, PFOA, PFNA, PFDA, and PFHxS, using complementary\n                  <jats:italic>in vivo<\/jats:italic>\n                  mouse and\n                  <jats:italic>in vitro<\/jats:italic>\n                  3D ovarian follicle culture models. Young adult female mice were exposed to a range of concentrations of the PFAS mixture (PFASmix) through daily drinking water for 8 weeks. PFASmix at high yet environmentally relevant concentrations (PFASmix-high) disrupted mouse estrous cyclicity, decreased circulating estradiol, increased testosterone, and promoted follicular atresia. Antral follicles from exposed mice showed decreased\n                  <jats:italic>Lhcgr<\/jats:italic>\n                  and increased\n                  <jats:italic>Amh<\/jats:italic>\n                  expression. Although the number of ovulated oocytes was unchanged following superovulation, PFASmix-high reduced oocyte size and polar body extrusion and altered oocyte cytoskeletal characteristics. In a 3D mouse ovarian follicle culture model, direct PFASmix exposure impaired follicle growth, ovulation, and oocyte maturation in a concentration-dependent manner. PFASmix-high suppressed the periovulatory expression of\n                  <jats:italic>Areg, Ereg, Tnfaip6,<\/jats:italic>\n                  and\n                  <jats:italic>Adamts1<\/jats:italic>\n                  and impaired corpus luteal (CL) development and function, as evidenced by reduced CL spheroid growth and cell survival, decreased expression of\n                  <jats:italic>Star, Cyp11a1, Hsd3b1,<\/jats:italic>\n                  and\n                  <jats:italic>Lhcgr<\/jats:italic>\n                  , and reduced progesterone secretion. PFASmix-high exposure additionally altered the expression of multiple PPAR\u03b3-associated genes in cultured ovarian follicles. Benchmark dose modeling identified estrous cyclicity and follicle rupture as sensitive\n                  <jats:italic>in vivo<\/jats:italic>\n                  and\n                  <jats:italic>in vitro<\/jats:italic>\n                  endpoints, respectively. Together, these findings demonstrate that exposure to the mixture of long-chain PFAS disrupts multiple stages of ovarian function, from follicular development, oocyte maturation to ovulation and luteal function, providing mechanistic and quantitative evidence for the reproductive toxicity of PFAS mixtures.\n                <\/jats:p>","DOI":"10.64898\/2026.09.12.750977","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:45:19Z","timestamp":1789757119000},"source":"Crossref","is-referenced-by-count":0,"title":["Exposure to a mixture of long-chain per- and polyfluoroalkyl substances (PFAS) disrupts ovarian follicle development, ovulation, and luteinization in female mice"],"prefix":"10.64898","author":[{"given":"Antonella R. R.","family":"Caceres","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Costanza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-7013","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Center for Environmental Exposures and Disease, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"12","key":"2026092214053023000_2026.09.12.750977v1.1","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1039\/D0EM00291G","article-title":"An overview of the uses of per- and polyfluoroalkyl substances (PFAS)","volume":"22","year":"2020","journal-title":"Environ Sci Process Impacts"},{"key":"2026092214053023000_2026.09.12.750977v1.2","doi-asserted-by":"crossref","unstructured":"Mashima R . Per- and Polyfluoroalkyl Substances (PFAS): History, Current Concerns, and Future Outlook. Molecules. 2025;30(22).","DOI":"10.3390\/molecules30224415"},{"key":"2026092214053023000_2026.09.12.750977v1.3","doi-asserted-by":"crossref","unstructured":"Ismanto A , Hadibarata T , Wahyuningsih C , Maslukah L , Wijaya YJ , Safinatunnajah N , et al. Per- and polyfluoroalkyl substances (PFAS): persistence, toxicity, and emerging solutions. Bioprocess Biosyst Eng. 2026.","DOI":"10.1007\/s00449-026-03317-7"},{"key":"2026092214053023000_2026.09.12.750977v1.4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/toxics12070455","article-title":"Effects of Per- and Polyfluoroalkylated Substances on Female Reproduction","volume":"12","year":"2024","journal-title":"Toxics"},{"key":"2026092214053023000_2026.09.12.750977v1.5","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10009"},{"key":"2026092214053023000_2026.09.12.750977v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-16395-6"},{"key":"2026092214053023000_2026.09.12.750977v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2013.06.004"},{"key":"2026092214053023000_2026.09.12.750977v1.8","unstructured":"Agency USEP. Fact Sheet: 2010\/2015 PFOA Stewardship Program: EPA; 2026 [Available from: https:\/\/www.epa.gov\/assessing-and-managing-chemicals-under-tsca\/fact-sheet-20102015-pfoa-stewardship-program#mfg."},{"key":"2026092214053023000_2026.09.12.750977v1.9","doi-asserted-by":"crossref","unstructured":"Jaus A , Fragniere Rime C , Riou J , Bruschweiler BJ , Bochud M , von Goetz N . Serum biomonitoring of per- and polyfluoroalkyl substances (PFASs) in the adult population of Switzerland: Results from the pilot phase of the Swiss health study. Environ Int. 2025;198:109382.","DOI":"10.1016\/j.envint.2025.109382"},{"key":"2026092214053023000_2026.09.12.750977v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2025.120916"},{"issue":"1","key":"2026092214053023000_2026.09.12.750977v1.11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12940-024-01085-z","article-title":"Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of adult female participants in the MIREC-ENDO study","volume":"23","year":"2024","journal-title":"Environ Health"},{"key":"2026092214053023000_2026.09.12.750977v1.12","doi-asserted-by":"crossref","unstructured":"Gockener B , Weber T , Rudel H , Bucking M , Kolossa-Gehring M . Human biomonitoring of per- and polyfluoroalkyl substances in German blood plasma samples from 1982 to 2019. Environ Int. 2020;145:106123.","DOI":"10.1016\/j.envint.2020.106123"},{"issue":"4","key":"2026092214053023000_2026.09.12.750977v1.13","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1021\/envhealth.4c00224","article-title":"Assessing the Impact of Serum Per- and Polyfluoroalkyl Substance Concentrations on Immune Function in an Industrialized Region of China","volume":"3","year":"2025","journal-title":"Environ Health (Wash"},{"issue":"5","key":"2026092214053023000_2026.09.12.750977v1.14","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41370-023-00536-y","article-title":"Occupational exposure to per- and polyfluoroalkyl substances: a scope review of the literature from 1980-2021","volume":"33","year":"2023","journal-title":"J Expo Sci Environ Epidemiol"},{"issue":"5","key":"2026092214053023000_2026.09.12.750977v1.15","doi-asserted-by":"crossref","first-page":"490","DOI":"10.2486\/indhealth.2025-0009","article-title":"High serum perfluorooctanoic acid (PFOA) concentrations and interstitial lung disease in former and current workers in a fluorochemical company","volume":"63","year":"2025","journal-title":"Ind Health"},{"key":"2026092214053023000_2026.09.12.750977v1.16","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.3c06499"},{"key":"2026092214053023000_2026.09.12.750977v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07359-6"},{"issue":"3","key":"2026092214053023000_2026.09.12.750977v1.18","first-page":"156323","article-title":"Per- and polyfluoroalkyl substances (PFAS) exposure in women seeking in vitro fertilization-embryo transfer treatment (IVF-ET) in China: Blood-follicular transfer and associations with IVF-ET outcomes","volume":"838","year":"2022","journal-title":"Sci Total Environ"},{"issue":"7","key":"2026092214053023000_2026.09.12.750977v1.19","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.ijheh.2018.07.009","article-title":"Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters","volume":"221","year":"2018","journal-title":"Int J Hyg Environ Health"},{"key":"2026092214053023000_2026.09.12.750977v1.20","doi-asserted-by":"crossref","unstructured":"Kang Q , Gao F , Zhang X , Wang L , Liu J , Fu M , et al. Nontargeted identification of per- and polyfluoroalkyl substances in human follicular fluid and their blood-follicle transfer. Environ Int. 2020;139:105686.","DOI":"10.1016\/j.envint.2020.105686"},{"key":"2026092214053023000_2026.09.12.750977v1.21","doi-asserted-by":"crossref","unstructured":"Liao Q , Tang P , Fan H , Song Y , Liang J , Huang H , et al. Association between maternal exposure to per- and polyfluoroalkyl substances and serum markers of liver function during pregnancy in China: A mixture-based approach. Environ Pollut. 2023;323:121348.","DOI":"10.1016\/j.envpol.2023.121348"},{"key":"2026092214053023000_2026.09.12.750977v1.22","doi-asserted-by":"crossref","unstructured":"Peng J , Gong R , Li R , Li L , Yu H , Wen Q . Perfluoroalkyl and polyfluoroalkyl substances exposure and liver disease: A review. Toxicology. 2026;525:154509.","DOI":"10.1016\/j.tox.2026.154509"},{"key":"2026092214053023000_2026.09.12.750977v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41370-024-00742-2"},{"key":"2026092214053023000_2026.09.12.750977v1.24","doi-asserted-by":"crossref","unstructured":"Steenland K , Winquist A . PFAS and cancer, a scoping review of the epidemiologic evidence. Environ Res. 2021;194:110690.","DOI":"10.1016\/j.envres.2020.110690"},{"issue":"1","key":"2026092214053023000_2026.09.12.750977v1.25","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s13643-024-02596-z","article-title":"Childhood PFAS exposure and immunotoxicity: a systematic review and meta-analysis of human studies","volume":"13","year":"2024","journal-title":"Syst Rev"},{"issue":"1","key":"2026092214053023000_2026.09.12.750977v1.26","doi-asserted-by":"crossref","first-page":"12502","DOI":"10.1038\/s41598-025-91977-y","article-title":"Per and polyfluoroalkyl substances affect thyroid hormones for people with a history of exposure from drinking water","volume":"15","year":"2025","journal-title":"Sci Rep"},{"issue":"5","key":"2026092214053023000_2026.09.12.750977v1.27","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41370-023-00545-x","article-title":"Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles","volume":"33","year":"2023","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"2026092214053023000_2026.09.12.750977v1.28","doi-asserted-by":"crossref","unstructured":"Lu R , Pang Y , Yu J , Zhang J . Health hazards of per- and polyfluoroalkyl substances via nuclear receptors. Environ Pollut. 2026;398:128063.","DOI":"10.1016\/j.envpol.2026.128063"},{"key":"2026092214053023000_2026.09.12.750977v1.29","doi-asserted-by":"crossref","first-page":"134642","DOI":"10.1016\/j.jhazmat.2024.134642","article-title":"Use of Tox21 screening data to profile PFAS bioactivities on nuclear receptors, cellular stress pathways, and cytochrome p450 enzymes","volume":"473","year":"2024","journal-title":"Journal of Hazardous Materials"},{"key":"2026092214053023000_2026.09.12.750977v1.30","doi-asserted-by":"crossref","unstructured":"Roy S , Moran J , Danasekaran K , O\u2019Brien K , Dakshanamurthy S . Large-Scale Screening of Per- and Polyfluoroalkyl Substance Binding Interactions and Their Mixtures with Nuclear Receptors. Int J Mol Sci. 2024;25(15).","DOI":"10.3390\/ijms25158241"},{"key":"2026092214053023000_2026.09.12.750977v1.31","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3390\/toxics12090678","article-title":"Per- and Polyfluoroalkyl Substances (PFAS) Affect Female Reproductive Health: Epidemiological Evidence and Underlying Mechanisms","volume":"12","year":"2024","journal-title":"Toxics"},{"key":"2026092214053023000_2026.09.12.750977v1.32","doi-asserted-by":"crossref","unstructured":"Shi W , Zhang Z , Li M , Dong H , Li J . Reproductive toxicity of PFOA, PFOS and their substitutes: A review based on epidemiological and toxicological evidence. Environ Res. 2024;250:118485.","DOI":"10.1016\/j.envres.2024.118485"},{"key":"2026092214053023000_2026.09.12.750977v1.33","doi-asserted-by":"crossref","unstructured":"Che J , Qu Y , Liu W , Zhang Y , Wu Z . Network toxicology and molecular simulation identify key genes and pathways in PFAS-induced premature ovarian insufficiency. Reprod Toxicol. 2025;138:109086.","DOI":"10.1016\/j.reprotox.2025.109086"},{"issue":"3","key":"2026092214053023000_2026.09.12.750977v1.34","doi-asserted-by":"crossref","first-page":"hoaf044","DOI":"10.1093\/hropen\/hoaf044","article-title":"Association between novel per-and poly-fluoroalkyl substances and premature ovarian insufficiency: a case-control study","volume":"2025","year":"2025","journal-title":"Hum Reprod Open"},{"key":"2026092214053023000_2026.09.12.750977v1.35","doi-asserted-by":"crossref","unstructured":"Harlow SD , Hood MM , Brooks R , Calafat AM , Randolph JF, Jr. , Gold EB , et al. Per- and polyfluoroalkyl substances (PFAS) and menstrual cycle characteristics in midlife women: The Study of Women\u2019s Health Across the Nation. Reprod Toxicol. 2026;141:109207.","DOI":"10.1016\/j.reprotox.2026.109207"},{"issue":"6","key":"2026092214053023000_2026.09.12.750977v1.36","doi-asserted-by":"crossref","first-page":"067012","DOI":"10.1289\/EHP1203","article-title":"Plasma Perfluoroalkyl and Polyfluoroalkyl Substances Concentration and Menstrual Cycle Characteristics in Preconception Women","volume":"125","year":"2017","journal-title":"Environ Health Perspect"},{"key":"2026092214053023000_2026.09.12.750977v1.37","doi-asserted-by":"crossref","unstructured":"Zhang Y , Martin L , Mustieles V , Ghaly M , Archer M , Sun Y , et al. Per- and polyfluoroalkyl substances exposure is associated with polycystic ovary syndrome risk among women attending a fertility clinic. Sci Total Environ. 2024;950:175313.","DOI":"10.1016\/j.scitotenv.2024.175313"},{"key":"2026092214053023000_2026.09.12.750977v1.38","doi-asserted-by":"crossref","unstructured":"Xu X , Zhang X , Chen J , Du X , Sun Y , Zhan L , et al. Exploring the molecular mechanisms by which per- and polyfluoroalkyl substances induce polycystic ovary syndrome through in silico toxicogenomic data mining. Ecotoxicol Environ Saf. 2024;275:116251.","DOI":"10.1016\/j.ecoenv.2024.116251"},{"key":"2026092214053023000_2026.09.12.750977v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2022.114718"},{"key":"2026092214053023000_2026.09.12.750977v1.40","doi-asserted-by":"crossref","unstructured":"Shen J , Mao Y , Zhang H , Lou H , Zhang L , Moreira JP , et al. Exposure of women undergoing in-vitro fertilization to per-and polyfluoroalkyl substances: Evidence on negative effects on fertilization and high-quality embryos. Environ Pollut. 2024;359:124474.","DOI":"10.1016\/j.envpol.2024.124474"},{"issue":"2","key":"2026092214053023000_2026.09.12.750977v1.41","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/toxsci\/kfy167","article-title":"Impact of Perfluorooctane Sulfonate on Reproductive Ability of Female Mice through Suppression of Estrogen Receptor alpha-Activated Kisspeptin Neurons","volume":"165","year":"2018","journal-title":"Toxicol Sci"},{"issue":"5","key":"2026092214053023000_2026.09.12.750977v1.42","doi-asserted-by":"crossref","first-page":"57024","DOI":"10.1289\/EHP14876","article-title":"Exposure to Long-and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: An in Vivo and in Vitro Study","volume":"133","year":"2025","journal-title":"Environ Health Perspect"},{"issue":"6","key":"2026092214053023000_2026.09.12.750977v1.43","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1021\/envhealth.5c00576","article-title":"Prenatal Exposure to PFOA Induces Ovarian Function Impairment via the Disruption of the PPARgamma\/ANGPTL4 Pathway","volume":"4","year":"2026","journal-title":"Environ Health (Wash"},{"issue":"5","key":"2026092214053023000_2026.09.12.750977v1.44","doi-asserted-by":"crossref","first-page":"e70052","DOI":"10.1002\/bdr2.70052","article-title":"Potential Effects of Prepubertal Exposure to Perfluorooctane Sulfonic Acid on the First Wave of Folliculogenesis in Young CD-1 Mice","volume":"118","year":"2026","journal-title":"Birth Defects Res"},{"key":"2026092214053023000_2026.09.12.750977v1.45","unstructured":"Stierman B , Afful J , Carroll MD , Chen TC , Davy O , Fink S , et al. National Health and Nutrition Examination Survey 2017-March 2020 Prepandemic Data Files-Development of Files and Prevalence Estimates for Selected Health Outcomes. Natl Health Stat Report. 2021(158)."},{"key":"2026092214053023000_2026.09.12.750977v1.46","unstructured":"Institute SS. Contamination Map 2026 [Available from: https:\/\/pfas-exchange.org\/tools\/contamination-map\/."},{"key":"2026092214053023000_2026.09.12.750977v1.47","unstructured":"NAVFAC. Marine Corps Base Camp Lejeune 2026 [Available from: https:\/\/www.navfac.navy.mil\/Divisions\/Environmental\/Products-and-Services\/Environmental-Restoration\/Mid-Atlantic\/Camp-Lejeune-MCB\/OBDW-PFAS\/#Links."},{"key":"2026092214053023000_2026.09.12.750977v1.48","unstructured":"Agency USEP. Fifth Unregulated Contaminant Monitoring Rule (UCMR 5) Data Finder. In: Agency USEP, editor.: U.S. Environmental Protection Agency; 2026."},{"key":"2026092214053023000_2026.09.12.750977v1.49","doi-asserted-by":"crossref","unstructured":"Bryan Stierman MD , M.P.H.; Joseph Afful , M.S.; Margaret D . Carroll, M.S.P.H. ; Te-Ching Chen, Ph.D. ; Orlando Davy,, M.P.H. ; Steven Fink MACDF M.S.P.H. ; Qiuping Gu, Ph.D. ; Craig M. Hales , M.D., M.P.H.; Jeffery P. Hughes ,, M.P.H.; Yechiam Ostchega PD , R.N.; Renee J. Storandt , M.T.(A.S.C.P.), M.S.P.H.; and Lara J. Akinbami , M.D. National Health and Nutrition Examination Survey 2017\u2013March 2020 Prepandemic Data Files\u2014Development of Files and Prevalence Estimates for Selected Health Outcomes. National Health Statistics Reports. 2021.","DOI":"10.15620\/cdc:106273"},{"key":"2026092214053023000_2026.09.12.750977v1.50","doi-asserted-by":"publisher","DOI":"10.1007\/s00420-007-0213-0"},{"key":"2026092214053023000_2026.09.12.750977v1.51","doi-asserted-by":"publisher","DOI":"10.1097\/01.jom.0000052958.59271.10"},{"key":"2026092214053023000_2026.09.12.750977v1.52","doi-asserted-by":"publisher","DOI":"10.1097\/00043764-199909000-00012"},{"key":"2026092214053023000_2026.09.12.750977v1.53","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioad009"},{"key":"2026092214053023000_2026.09.12.750977v1.54","doi-asserted-by":"crossref","unstructured":"Ongaro L , Alonso CAI , Zhou X , Brule E , Li Y , Schang G , et al. Development of a Highly Sensitive ELISA for Measurement of FSH in Serum, Plasma, and Whole Blood in Mice. Endocrinology. 2021;162(4).","DOI":"10.1210\/endocr\/bqab014"},{"key":"2026092214053023000_2026.09.12.750977v1.55","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1502"},{"key":"2026092214053023000_2026.09.12.750977v1.56","doi-asserted-by":"crossref","unstructured":"Qiu A , Luo K , Liu H , Huang J , Liu X , Zhang J , et al. Associations between per-and polyfluoroalkyl substances and menstrual cycle regularity in reproductive-aged female: A cross-sectional study. Emerging Contaminants. 2025;11(1).","DOI":"10.1016\/j.emcon.2024.100438"},{"key":"2026092214053023000_2026.09.12.750977v1.57","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det390"},{"issue":"11","key":"2026092214053023000_2026.09.12.750977v1.58","doi-asserted-by":"crossref","first-page":"e4427","DOI":"10.1210\/clinem\/dgab476","article-title":"Per-and Polyfluoroalkyl Substances and Hormone Levels During the Menopausal Transition","volume":"106","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2026092214053023000_2026.09.12.750977v1.59","doi-asserted-by":"crossref","unstructured":"Xie X , Weng X , Liu S , Chen J , Guo X , Gao X , et al. Perfluoroalkyl and Polyfluoroalkyl substance exposure and association with sex hormone concentrations: Results from the NHANES 2015-2016. Environ Sci Eur. 2021;33(1).","DOI":"10.1186\/s12302-021-00508-9"},{"key":"2026092214053023000_2026.09.12.750977v1.60","doi-asserted-by":"crossref","unstructured":"Fang YW , Chen CW , Lin HC , Su TC , Wang C , Lin CY . Associations Between PFAS Exposure and HPG Axis Hormones in U.S. Women. Life (Basel). 2025;15(12).","DOI":"10.3390\/life15121923"},{"key":"2026092214053023000_2026.09.12.750977v1.61","doi-asserted-by":"crossref","unstructured":"He Y , Hu C , Zhang Y , Fan X , Gao W , Fang J , et al. Association of perfluoroalkyl and polyfluoroalkyl substances with sex hormones in children and adolescents 6-19 Years of age. Environ Pollut. 2023;329:121707.","DOI":"10.1016\/j.envpol.2023.121707"},{"key":"2026092214053023000_2026.09.12.750977v1.62","doi-asserted-by":"crossref","unstructured":"Liu Y , Calafat AM , Chen A , Lanphear BP , Jones NY , Cecil KM , et al. Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study. Sci Total Environ. 2023;890:164353.","DOI":"10.1016\/j.scitotenv.2023.164353"},{"key":"2026092214053023000_2026.09.12.750977v1.63","doi-asserted-by":"crossref","unstructured":"Wang Y , Aimuzi R , Nian M , Zhang Y , Luo K , Zhang J . Perfluoroalkyl substances and sex hormones in postmenopausal women: NHANES 2013-2016. Environ Int. 2021;149:106408.","DOI":"10.1016\/j.envint.2021.106408"},{"key":"2026092214053023000_2026.09.12.750977v1.64","doi-asserted-by":"crossref","unstructured":"Rodriguez-Carrillo A , Remy S , Koppen G , Wauters N , Freire C , Olivas-Martinez A , et al. PFAS association with kisspeptin and sex hormones in teenagers of the HBM4EU aligned studies. Environ Pollut. 2023;335:122214.","DOI":"10.1016\/j.envpol.2023.122214"},{"key":"2026092214053023000_2026.09.12.750977v1.65","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00075"},{"key":"2026092214053023000_2026.09.12.750977v1.66","doi-asserted-by":"crossref","unstructured":"Johnson GR , Brusseau ML , Carroll KC , Tick GR , Duncan CM . Global distributions, source-type dependencies, and concentration ranges of per- and polyfluoroalkyl substances in groundwater. Sci Total Environ. 2022;841:156602.","DOI":"10.1016\/j.scitotenv.2022.156602"},{"issue":"4","key":"2026092214053023000_2026.09.12.750977v1.67","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41561-024-01402-8","article-title":"Underestimated burden of per- and polyfluoroalkyl substances in global surface waters and groundwaters","volume":"17","year":"2024","journal-title":"Nature Geoscience"},{"key":"2026092214053023000_2026.09.12.750977v1.68","doi-asserted-by":"crossref","unstructured":"Fu J , Gao Y , Cui L , Wang T , Liang Y , Qu G , et al. Occurrence, temporal trends, and half-lives of perfluoroalkyl acids (PFAAs) in occupational workers in China. Sci Rep. 2016;6:38039.","DOI":"10.1038\/srep38039"},{"issue":"2","key":"2026092214053023000_2026.09.12.750977v1.69","first-page":"2018","article-title":"Per and polyfluoroalkyl substances (PFAS) blood levels after contamination of a community water supply and comparison with 2013\u20132014 NHANES","volume":"29","year":"2018","journal-title":"Journal of Exposure Science & Environmental Epidemiology"},{"key":"2026092214053023000_2026.09.12.750977v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2017.10.026"},{"key":"2026092214053023000_2026.09.12.750977v1.71","doi-asserted-by":"crossref","unstructured":"Zurlinden TJ , Dzierlenga MW , Kapraun DF , Ring C , Bernstein AS , Schlosser PM , et al. Estimation of species- and sex-specific PFAS pharmacokinetics in mice, rats, and non-human primates using a Bayesian hierarchical methodology. Toxicol Appl Pharmacol. 2025;499:117336.","DOI":"10.1016\/j.taap.2025.117336"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.12.750977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:05:51Z","timestamp":1790111151000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.12.750977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":71,"URL":"https:\/\/doi.org\/10.64898\/2026.09.12.750977","relation":{},"subject":[],"published":{"date-parts":[[2026,9,18]]},"subtype":"preprint"}}