{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:37Z","timestamp":1792790317008,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Developmental Biology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of General Medical Sciences","award":["1R16GM145545"],"award-info":[{"award-number":["1R16GM145545"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Alcohol Abuse and Alcoholism","award":["U54 AA019765"],"award-info":[{"award-number":["U54 AA019765"]}],"id":[{"id":"https:\/\/ror.org\/02jzrsm59","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Minority Health and Health Disparities","award":["U54 MD012392"],"award-info":[{"award-number":["U54 MD012392"]}],"id":[{"id":"https:\/\/ror.org\/0493hgw16","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Prenatal alcohol exposure (PAE) can produce persistent alterations in mammary development and increase susceptibility to mammary tumorigenesis, but the early molecular events underlying these effects remain poorly understood. Here, we examined whether PAE alters the molecular program of the mammary gland at birth. Pregnant MMTV-ErbB2 mice received control or ethanol-containing liquid diets during gestation, and mammary tissues were collected from newborn female offspring. RNA sequencing revealed exposure-level-dependent transcriptional reprogramming, with substantially broader alterations following moderate compared with lower ethanol exposure. Pathway analyses identified prominent changes in metabolic and growth-regulatory networks, including insulin signaling, with coordinated alterations in components of the insulin\/IGF-IRS-PI3K\/AKT pathway. Biochemical analyses further demonstrated exposure-dependent changes in IGFBP expression and IRS1 abundance and phosphorylation, supporting remodeling of insulin\/IGF-associated signaling. Transcriptomic analyses also revealed enrichment of RNA metabolic and translational processes and, particularly following moderate exposure, enhanced DNA-replication, cell-cycle, and mitotic programs. These molecular signatures were accompanied by increased proliferative features in newborn mammary tissue. Together, these findings demonstrate that PAE establishes substantial molecular reprogramming of the mammary gland by birth and identify altered insulin\/metabolic signaling and proliferative programming as prominent features of this early developmental response.<\/jats:p>","DOI":"10.64898\/2026.09.22.753596","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:00:11Z","timestamp":1790172011000},"source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Analysis of the Newborn Mammary Gland Identifies Prenatal Ethanol-Induced Remodeling of Insulin Signaling and Enhanced Proliferative Programming"],"prefix":"10.64898","author":[{"given":"Zhikun","family":"Ma","sequence":"first","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda B","family":"Parris","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Yang","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute"},{"name":"Department of Biological and Biomedical Sciences, North Carolina Central University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC, 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092610000695000_2026.09.22.753596v1.1","doi-asserted-by":"crossref","unstructured":"Mabasa L , Kotze A , Sangweni NF , Willmer T , Gabuza KB , Patel O , Omoruyi SI , Burns A , Johnson R : Fetal Mammary Gland Development and Offspring\u2019s Breast Cancer Risk in Adulthood. 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