{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:42Z","timestamp":1792789722530,"version":"4.5.0"},"reference-count":114,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"crossref","award":["25-75-20026"],"award-info":[{"award-number":["25-75-20026"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"crossref"},{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"crossref"}]},{"award":["25-75-20026"],"award-info":[{"award-number":["25-75-20026"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Bisphenol A (BPA) is a widespread plasticizer widely used in the food industry worldwide. However, a consensus on the safe level of its daily intake does not currently exist, while there are numerous data pointing to a link between prenatal exposure to BPA and early neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The global average human-equivalent dose of BPA is estimated at 30 ng\/kg body weight\/day. Thus, the research herein was conducted on newborn and juvenile rat offspring of both sexes delivered from rats treated with 30 ng\/kg body weight\/day orally from day 6 to 21 of pregnancy and for a further 21 days during lactation. Our data indicate that prenatal exposure to 30 ng\/kg\/day from gestation day 6 to delivery induced sexually dimorphic, region-specific alterations in the neonatal (PD1) rat brains, impacting inflammatory reactions, estrogen receptor signaling, and neural progenitor dynamics. Prenatally BPA-treated males exhibited a pro-inflammatory state characterized by an increased total number of ramified Iba1+ microglia cells in the hippocampus alongside upregulation of Aif1, Nfkb, Tnf, Il1b, and Hif1a. Conversely, prenatally BPA-treated females showed only an increased total number of hippocampal Iba1+ cells and displayed inflammatory resilience, lacking upregulation of these markers. Both sexes exhibited a pro-inflammatory state in the prefrontal cortex via upregulation of Nfkb, Tnf, Il1b, and Hif1a. While both sexes showed decreased Tgfb in the prefrontal cortex, they deployed distinct compensatory responses: males upregulated the neuroprotector Igf1 only in the hippocampus, whereas in females, it was upregulated in both the hippocampus and the prefrontal cortex. Estrogen receptor expression was also highly dimorphic. In the hippocampus, males displayed an imbalance via Esr1 upregulation and Esr2 downregulation, while females showed Esr2 downregulation alone. In the prefrontal cortex, these transcriptional profiles were the opposite. Finally, neural progenitor markers were altered. In the prefrontal cortex, BPA drove the upregulation of Sox2 and Pax6 in males but Sox9 in females; in the hippocampus, only Pax6 was upregulated, and only in males. The PAX6 protein level in the hippocampus was significantly increased in males but decreased in females. In juvenile offspring (PD21), behavioral patterns characterized by hyper-exploration, increased environmental investigation, and heightened emotional reactivity during social exposure were more pronounced in female offspring. These baseline neonatal disparities followed by behavioral changes underscore the necessity of sex-specific approaches when evaluating early-life neurodevelopment and subsequent adult behavioral and biological vulnerabilities.<\/jats:p>","DOI":"10.3390\/life16091526","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal and Lactation Exposure to Bisphenol A (BPA) at the Global Mean Daily Intake Level Leads to Sex-Dependent Changes in Microglial State, Gene Expression, and Behavioral Patterns in Newborn and Juvenile Wistar Rat Offspring"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6744-2139","authenticated-orcid":false,"given":"Andrey D.","family":"Gerasimov","sequence":"first","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra V.","family":"Sentyabreva","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Elena A.","family":"Gantsova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-6828","authenticated-orcid":false,"given":"Ekaterina A.","family":"Melnikova","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-1799","authenticated-orcid":false,"given":"Anna M.","family":"Kosyreva","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418 Moscow, Russia"},{"name":"Research Institute of Molecular and Cellular Medicine, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 30). 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