{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:47:39Z","timestamp":1789181259711,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Many previous studies have indicated the adverse effects of bisphenol A (BPA) on sperm production and quality; however, the mechanisms underlying BPA male reproductive toxicity have yet to be elucidated. The main purpose of this study was to investigate the effect of perinatal exposure to BPA on the spermatogenic capacity of male offspring, and to explore the possible influence of inflammatory responses in BPA reproductive toxicity. Twenty-one pregnant C57BL\/6mice were randomly divided into three groups: a control group, a group receiving 0.2 \u03bcg\/mL (LBPA), and a group receiving 2 \u03bcg\/mL of BPA (HBPA), all via drinking water from gestational day 6 to the end of lactation. After weaning, one male mouse was randomly selected from each group (n = 7\/group); these three mice were fed a normal diet and drinking water for 1 month. Levels of serum testosterone (T) and tumor necrosis factor (TNF)-\u03b1 were then measured in all mice. Sperm count and the proportion of sperm malformation were also determined. The levels of Toll-like receptor 4 (TLR4), nuclear factor (NF)-\u03baB, and aryl hydrocarbon receptor (AhR) protein expression in the testis tissue were determined. Analysis showed that the proportion of sperm malformation increased in the LBPA and HBPA groups (p &lt; 0.05). Sperm count significantly decreased only in the HBPA group (p &lt; 0.05), while the levels of serum TNF-\u03b1 increased in the LBPA and HBPA groups (p &lt; 0.05). Levels of serum T decreased significantly in the HBPA group, compared with controls (p &lt; 0.05). Levels of TLR4 and NF-\u03baB protein expression in the testis were significantly higher in the LBPA and HBPA groups (p &lt; 0.05 or p &lt; 0.01), while AhR protein expression was higher and seminiferous tubules in the testis showed more damage in the HBPA group compared to controls (p &lt; 0.05 and p &lt; 0.01, respectively). Our results showed that perinatal exposure to low or high doses of BPA decreased the capacity for spermatogenesis in male offspring, which may be associated with an inflammatory response activated by the TLR4\/ NF-\u03baB and AhR signaling pathways in the testis.<\/jats:p>","DOI":"10.3390\/ijerph15102158","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T08:23:50Z","timestamp":1538468630000},"page":"2158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Decreased Capacity for Sperm Production Induced by Perinatal Bisphenol A Exposure Is Associated with an Increased Inflammatory Response in the Offspring of C57BL\/6 Male Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuan","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Anifandis, G., Amiridis, G., Dafopoulos, K., Daponte, A., Dovolou, E., Gavriil, E., Gorgogietas, V., Kachpani, E., Mamuris, Z., and Messini, C.I. (2017). The in vitro impact of the herbicide roundup on human sperm motility and sperm mitochondria. Toxics, 6.","DOI":"10.3390\/toxics6010002"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Anifandis, G., Katsanaki, K., Lagodonti, G., Messini, C., Simopoulou, M., Dafopoulos, K., and Daponte, A. (2018). The effect of glyphosate on human sperm motility and sperm DNA fragmentation. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15061117"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tox.2015.06.011","article-title":"Evaluation of the reproductive toxicity of fungicide propiconazole in male rats","volume":"335","author":"Costa","year":"2015","journal-title":"Toxicology"},{"key":"ref_4","first-page":"5","article-title":"Health risk of exposure to Bisphenol A (BPA)","volume":"66","author":"Konieczna","year":"2015","journal-title":"Roczniki Pa\u0144stwowego Zak\u0142adu Higieny"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6523","DOI":"10.1021\/acsomega.8b00824","article-title":"Exposure to bisphenol A, bisphenol F, and bisphenol S in U.S. adults and children: The national health and nutrition examination survey 2013\u20132014","volume":"3","author":"Lehmler","year":"2018","journal-title":"ACS Omega"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.chemosphere.2013.12.085","article-title":"Determination of free bisphenol A (BPA) concentrations in breast milk of U.S. women using a sensitive LC\/MS\/MS method","volume":"104","author":"Zimmers","year":"2014","journal-title":"Chemosphere"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.scitotenv.2017.10.042","article-title":"Bisphenol A distribution in serum, urine, placenta, breast milk, and umbilical cord serum in a birth panel of mother-neonate pairs","volume":"626","author":"Lee","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_8","first-page":"20","article-title":"Bisphenol A: A threat to human health","volume":"77","author":"Srivastava","year":"2015","journal-title":"J. Environ. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.fertnstert.2010.09.026","article-title":"Urine bisphenol-A (BPA) level in relation to semen quality","volume":"95","author":"Li","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.envint.2018.05.003","article-title":"Associations of female exposure to bisphenol A with fecundability: Evidence from a preconception cohort study","volume":"117","author":"Wang","year":"2018","journal-title":"Environ. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.reprotox.2016.05.003","article-title":"Differential effects of bisphenol A and estradiol on rat spermatogenesis\u2019 establishment","volume":"63","author":"Brouard","year":"2016","journal-title":"Reprod. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1745-7262.2008.00292.x","article-title":"Effects of estradiol-17 beta and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups\u2019 reproductive system","volume":"10","author":"Okada","year":"2008","journal-title":"Asian J. Androl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1289\/ehp.1307728","article-title":"Bisphenol a and reproductive health: Update of experimental and human evidence, 2007\u20132013","volume":"122","author":"Peretz","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3585809","DOI":"10.1155\/2017\/3585809","article-title":"Bisphenol A exposure during pregnancy alters the mortality and levels of reproductive hormones and genes in offspring mice","volume":"2017","author":"Ma","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1289\/ehp.7155","article-title":"In vivo imaging of activated estrogen receptors in utero by estrogens and bisphenol A","volume":"112","author":"Lemmen","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.111.095349","article-title":"The industrial chemical bisphenol A (BPA) interferes with proliferative activity and development of steroidogenic capacity in rat Leydig cells","volume":"86","author":"Nanjappa","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.aquatox.2017.10.008","article-title":"Juvenile exposure to bisphenol A promotes ovarian differentiation but suppresses its growth-potential involvement of pituitary follicle-stimulating hormone","volume":"193","author":"Chen","year":"2017","journal-title":"Aquat. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tox.2017.06.007","article-title":"Anti-androgenic mechanisms of bisphenol A involve androgen receptor signaling pathway","volume":"387","author":"Wang","year":"2017","journal-title":"Toxicology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.reprotox.2017.06.134","article-title":"Effects of bisphenol A analogues on reproductive functions in mice","volume":"73","author":"Shi","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e676","DOI":"10.1038\/cddis.2013.203","article-title":"Exposure to bisphenol A disrupts meiotic progression during spermatogenesis in adult rats through estrogen-like activity","volume":"4","author":"Liu","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2058738418774897","DOI":"10.1177\/2058738418774897","article-title":"Exposure to low-dose bisphenol A during the juvenile period of development disrupts the immune system and aggravates allergic airway inflammation in mice","volume":"32","author":"Koike","year":"2018","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.envres.2017.07.005","article-title":"Bisphenol A induces COX-2 through the mitogen-activated protein kinase pathway and is associated with levels of inflammation-related markers in elderly populations","volume":"158","author":"Song","year":"2017","journal-title":"Environ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tox.2015.01.002","article-title":"Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis","volume":"329","author":"Wisniewski","year":"2015","journal-title":"Toxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10606","DOI":"10.18632\/oncotarget.7218","article-title":"Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells","volume":"7","author":"Xie","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Eladak, S., Moison, D., Guerquin, M.J., Matilionyte, G., Kilcoyne, K., N\u2019Tumba-Byn, T., Messiaen, S., Deceuninck, Y., Pozzi-Gaudin, S., and Benachi, A. (2018). Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191934"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.yhbeh.2017.12.001","article-title":"Opening the black box of endocrine disruption of brain development: Lessons from the characterization of Bisphenol A","volume":"101","author":"Nesan","year":"2018","journal-title":"Horm. Behav."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Valentino, R., D\u2019Esposito, V., Passaretti, F., Liotti, A., Cabaro, S., Longo, M., Perruolo, G., Oriente, F., Beguinot, F., and Formisano, P. (2013). Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082099"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.crvi.2017.07.007","article-title":"Endocrine disruptors (EDs) and hormone-dependent cancers: Correlation or causal relationship?","volume":"340","author":"Rochefort","year":"2017","journal-title":"C. R. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s40618-015-0336-1","article-title":"Bisphenol A environmental exposure and the detrimental effects on human metabolic health: Is it necessary to revise the risk assessment in vulnerable population?","volume":"39","author":"Valentino","year":"2016","journal-title":"J. Endocrinol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3109\/19396368.2011.574248","article-title":"Molecular changes induced by bisphenol-A in rat Sertoli cell culture","volume":"57","author":"Izumi","year":"2011","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/bcpt.12894","article-title":"Bisphenol A exposure impairsepididymal development during the peripubertal period of rats: Inflammatory profile and tissue changes","volume":"122","author":"Ogo","year":"2018","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1021\/tx7001965","article-title":"The search for endogenous activators of the aryl hydrocarbon receptor","volume":"21","author":"Nguyen","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00018-015-2056-2","article-title":"The emerging role of aryl hydrocarbon receptor in the activation and differentiation of Th17 cells","volume":"73","author":"Baricza","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12426","DOI":"10.3390\/ijerph121012426","article-title":"Exposure to endocrine disruptors and nuclear receptors gene expression in infertile and fertile men from Italian Areas with different environmental features","volume":"12","author":"Tait","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10146","DOI":"10.3390\/ijerph111010146","article-title":"Exposure to endocrine disrupters and nuclear receptor gene expression in infertile and fertile women from different Italian areas","volume":"11","author":"Tait","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.reprotox.2013.07.022","article-title":"Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway","volume":"42","author":"Craig","year":"2013","journal-title":"Reprod. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1365-2567.2009.03054.x","article-title":"The aryl hydrocarbon receptor: A perspective on potential roles in the immune system","volume":"127","author":"Stevens","year":"2009","journal-title":"Immunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.abb.2011.05.011","article-title":"Interaction of aryl hydrocarbon receptor and NF-\u03baB subunit RelB in breast cancer is associated with interleukin-8 overexpression","volume":"512","author":"Vogel","year":"2011","journal-title":"Arch. Biochem. Biophys."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/15\/10\/2158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:23:30Z","timestamp":1760196210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/15\/10\/2158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,1]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijerph15102158"],"URL":"https:\/\/doi.org\/10.3390\/ijerph15102158","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,1]]}}}