{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:29Z","timestamp":1760145809343,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004317","name":"High-Level Foundation of Shihezi University","doi-asserted-by":"publisher","award":["KX015201"],"award-info":[{"award-number":["KX015201"]}],"id":[{"id":"10.13039\/501100004317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>This study examines the impact of Bisphenol A (BPA), a prevalent environmental estrogenic toxicant, on the ovarian development of mice. Mice were exposed to varying BPA doses from in utero to postnatal stages, up to weaning (day 21, PND 21) and puberty (day 45, PND 45). The BPA content in the serum of the offspring mice on PND 45 was higher than that of the mice sacrificed at PND 21. However, the ovary organ index of the mice of PND 21 was significantly increased, and the ovarian structure was damaged when exposed to BPA. In contrast, the mice with PND 45 did not show apparent ovarian lesions. On the other hand, granulosa cell apoptosis was detected in both PND 21 and PND 45 mice ovaries, and ER\u03b2 was increased under the influence of BPA. Transcriptomic analysis revealed BPA\u2019s significant impact on ribosomal gene expression, marked downregulation of Rpl21 and Rpsa, and upregulation of Rps2 in both age groups. These transcriptomic alterations were further corroborated by real-time PCR, highlighting a dose-dependent effect of BPA on Rps2. Our findings confirm BPA\u2019s detrimental effects on ovarian health, with more pronounced damage in younger mice, suggesting heightened vulnerability in this group. The study underscores ribosomes as critical targets in BPA-induced ovarian developmental disruptions.<\/jats:p>","DOI":"10.3390\/toxics12090627","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T10:01:51Z","timestamp":1724666511000},"page":"627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bisphenol A Disrupts Ribosome Function during Ovarian Development of Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Xin","family":"Ma","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-8902","authenticated-orcid":false,"given":"Yongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, College of Agriculture and Environmental Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiyue","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"},{"name":"Xinjiang Tycoon Group Co., Ltd., Changji 831100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127097","DOI":"10.1016\/j.jhazmat.2021.127097","article-title":"The hazardous threat of Bisphenol A: Toxicity, detection and remediation","volume":"423","author":"Tarafdar","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.aquatox.2015.10.020","article-title":"Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects","volume":"169","author":"Chen","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.watres.2017.07.006","article-title":"Corrosion protection products as a source of bisphenol A and toxicity to the aquatic environment","volume":"123","author":"Vermeirssen","year":"2017","journal-title":"Water Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114709","DOI":"10.1016\/j.taap.2019.114709","article-title":"Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo","volume":"380","author":"Pinto","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.aquaculture.2018.07.057","article-title":"High levels of the endocrine disruptors bisphenol-A and 17\u03b2-estradiol detected in populations of green mussel, Perna viridis, cultured in the Gulf of Thailand","volume":"497","author":"Ocharoen","year":"2018","journal-title":"Aquaculture"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"130878","DOI":"10.1016\/j.foodchem.2021.130878","article-title":"Non-volatile molecular composition and discrimination of single grape white wines of Chardonnay, Riesling, Sauvignon Blanc and Silvaner using untargeted GC-MS analysis","volume":"369","author":"Khakimov","year":"2022","journal-title":"Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1080\/19393210.2019.1650835","article-title":"BPA, BPB, BPF, BADGE and BFDGE in canned beers from the Italian market","volume":"12","author":"Cirillo","year":"2019","journal-title":"Food Addit. Contam. Part B"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Abulehia, H.F., Mohd Nor, N.S., and Sheikh Abdul Kadir, S.H. (2022). The Current findings on the impact of prenatal BPA exposure on metabolic parameters: In vivo and epidemiological evidence. Nutrients, 14.","DOI":"10.3390\/nu14132766"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3082438","DOI":"10.1155\/2018\/3082438","article-title":"Damaging effects of bisphenol A on the kidney and the protection by melatonin: Emerging evidences from in vivo and in vitro studies","volume":"2018","author":"Kobroob","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.emcon.2019.08.002","article-title":"Free bisphenol A (BPA), BPA-Glucuronide (BPA-G), and total BPA concentrations in maternal serum and urine during pregnancy and umbilical cord blood at delivery","volume":"5","author":"Foster","year":"2019","journal-title":"Emerg. Contam."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1021\/acs.est.0c00206","article-title":"Technology: Occurrence and maternal transfer of multiple bisphenols, including an emerging derivative with unexpectedly high concentrations, in the human maternal\u2013fetal\u2013placental unit","volume":"54","author":"Pan","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8459","DOI":"10.1007\/s11356-019-04228-9","article-title":"A mini review of bisphenol A (BPA) effects on cancer-related cellular signaling pathways","volume":"26","author":"Nomiri","year":"2019","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.toxrep.2017.12.013","article-title":"Bisphenol A (BPA) the mighty and the mutagenic","volume":"5","author":"Jalal","year":"2018","journal-title":"Toxicol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107250","DOI":"10.1016\/j.envint.2022.107250","article-title":"G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ER\u03b1 and ER\u03b2 in pancreatic beta cells","volume":"164","author":"Encinar","year":"2022","journal-title":"Environ. Int."},{"key":"ref_15","unstructured":"Shelby, M.D. (2008). NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A. NTP CERHR MON, vii\u2013ix."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"bqaa171","DOI":"10.1210\/endocr\/bqaa171","article-title":"Update on the health effects of bisphenol A: Overwhelming evidence of harm","volume":"162","author":"Vandenberg","year":"2021","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1600248","DOI":"10.1002\/advs.201600248","article-title":"Low-dose bisphenol A exposure: A seemingly instigating carcinogenic effect on breast cancer","volume":"4","author":"Wang","year":"2017","journal-title":"Adv. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127005","DOI":"10.1289\/EHP6875","article-title":"Low-dose bisphenol a in a rat model of endometrial cancer: A CLARITY-BPA study","volume":"128","author":"Leung","year":"2020","journal-title":"Environ. Health Perspect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111429","DOI":"10.1016\/j.ecoenv.2020.111429","article-title":"Bisphenol A induces apoptosis through GPER-dependent activation of the ROS\/Ca2+-ASK1-JNK pathway in human granulosa cell line KGN","volume":"208","author":"Huang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tang, Z.-R., Xu, X.-L., Deng, S.-L., Lian, Z.-X., and Yu, K. (2020). Oestrogenic endocrine disruptors in the placenta and the fetus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041519"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.reprotox.2019.04.005","article-title":"Parental perinatal exposure to bisphenol A reduces the threshold to disrupt blastocyst implantation via decreasing talin, occudin and E-cadherin levels","volume":"86","author":"Morimoto","year":"2019","journal-title":"Reprod. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.2144\/000112517","article-title":"ImageJ for microscopy","volume":"43","author":"Collins","year":"2007","journal-title":"Biotechniques"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Garcia, T.I., Shen, Y., Crawford, D., Oleksiak, M.F., Whitehead, A., and Walter, R.B. (2012). RNA-Seq reveals complex genetic response to deepwater horizon oil release in Fundulus grandis. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-474"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/bioinformatics\/btt087","article-title":"EBSeq: An empirical Bayes hierarchical model for inference in RNA-seq experiments","volume":"29","author":"Leng","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1289\/ehp.0800376","article-title":"Bisphenol A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both","volume":"117","author":"Stahlhut","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1080\/1080-700291905846","article-title":"A multimedia assessment of the environmental fate of bisphenol A","volume":"8","author":"Cousins","year":"2002","journal-title":"Hum. Ecol. Risk Assess."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1039\/D2GC02726G","article-title":"Synthetic (bio) degradable polymers\u2013when does recycling fail?","volume":"25","author":"Agostinho","year":"2023","journal-title":"Green Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.emcon.2018.06.001","article-title":"Contaminants of emerging concern in landfill leachate in China: A review","volume":"4","author":"Qi","year":"2018","journal-title":"Emerg. Contam."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"146905","DOI":"10.1016\/j.scitotenv.2021.146905","article-title":"Biomonitoring of occupational exposure to bisphenol A, bisphenol S and bisphenol F: A systematic review","volume":"783","author":"Bousoumah","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lucarini, F., Krasniqi, T., Bailat Rosset, G., Roth, N., Hopf, N.B., Broillet, M.-C., and Staedler, D. (2020). Exposure to new emerging bisphenols among young children in Switzerland. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17134793"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eabd1159","DOI":"10.1126\/sciadv.abd1159","article-title":"Gestational low-dose BPA exposure impacts suprachiasmatic nucleus neurogenesis and circadian activity with transgenerational effects","volume":"7","author":"Nesan","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.cca.2018.06.041","article-title":"Interfering effects of bisphenol A on in vitro growth of preantral follicles and maturation of oocyes","volume":"485","author":"Wang","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1515\/reveh-2020-0032","article-title":"Bisphenol-A and polycystic ovary syndrome: A review of the literature","volume":"35","author":"Kechagias","year":"2020","journal-title":"Rev. Environ. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.dsx.2021.03.031","article-title":"Endocrine disrupting chemical Bisphenol A and its potential effects on female health","volume":"15","author":"Kawa","year":"2021","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.1002\/jcb.26872","article-title":"Bisphenol A (BPA) binding on full-length architectures of estrogen receptor","volume":"119","author":"Liu","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"bqad063","DOI":"10.1210\/endocr\/bqad063","article-title":"ER\u03b2 in granulosa cell tumors and its clinical potential","volume":"164","author":"Birgersson","year":"2023","journal-title":"Endocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s43032-022-00932-z","article-title":"Synthesis, regulatory factors, and signaling pathways of estrogen in the ovary","volume":"30","author":"Xiao","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111208","DOI":"10.1016\/j.mce.2021.111208","article-title":"ER\u03b2 regulated ovarian kisspeptin plays an important role in oocyte maturation","volume":"527","author":"Chakravarthi","year":"2021","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, S.-X., Ding, Z.-M., Ahmad, M.J., Wang, Y.-S., Duan, Z.-Q., Miao, Y.-L., Xiong, J.-J., and Huo, L.-J. (2020). Bisphenol B exposure disrupts mouse oocyte meiotic maturation in vitro through affecting spindle assembly and chromosome alignment. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.616771"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mesnage, R., Phedonos, A., Arno, M., Balu, S., Corton, J.C., and Antoniou, M.N. (2017). Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells. bioRxiv.","DOI":"10.1101\/112862"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Iwamoto, M., Masuya, T., Hosose, M., Tagawa, K., Ishibashi, T., Suyama, K., Nose, T., Yoshihara, E., Downes, M., and Evans, R.M. (2021). Bisphenol A derivatives act as novel coactivator-binding inhibitors for estrogen receptor \u03b2. J. Biol. Chem., 297.","DOI":"10.1101\/2021.05.10.443431"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101579","DOI":"10.1016\/j.beem.2021.101579","article-title":"Endocrine-disrupting chemicals and their effects on puberty","volume":"35","author":"Franssen","year":"2021","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144535","DOI":"10.1016\/j.gene.2020.144535","article-title":"Bisphenol A affects ovarian development in adolescent mice caused by genes expression change","volume":"740","author":"Wu","year":"2020","journal-title":"Gene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41423-021-00792-8","article-title":"Protein synthesis, degradation, and energy metabolism in T cell immunity","volume":"19","author":"Marchingo","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1093\/ced\/llad102","article-title":"A novel heterozygous missense variant in ribosomal protein L21 associated with familial hypotrichosis simplex","volume":"48","author":"Rayinda","year":"2023","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhu, J., Long, T., Gao, L., Zhong, Y., Wang, P., Wang, X., Li, Z., and Hu, Z. (2023). RPL21 interacts with LAMP3 to promote colorectal cancer invasion and metastasis by regulating focal adhesion formation. Cell. Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00443-y"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12900","DOI":"10.1093\/nar\/gkaa1108","article-title":"PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)","volume":"48","author":"Bergeron","year":"2020","journal-title":"Nucleic Acids Res."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/9\/627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:00Z","timestamp":1760110980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/9\/627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,26]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["toxics12090627"],"URL":"https:\/\/doi.org\/10.3390\/toxics12090627","relation":{},"ISSN":["2305-6304"],"issn-type":[{"type":"electronic","value":"2305-6304"}],"subject":[],"published":{"date-parts":[[2024,8,26]]}}}