{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:10:43Z","timestamp":1780463443018,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The increased production of industrial chemicals has led to greater human exposure to endocrine disruptors, such as diethylhexyl phthalate (DEHP). This plasticizer, widely used in hygiene products, packaging, and medical devices, does not covalently bind to polymeric materials, which facilitates its migration and subsequent entry into the human body, primarily via the oral route. In this study, we investigated the effects of DEHP exposure during the lactation period within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. The experimental model utilized Wistar female rats (n=9) that were placed for mating. Litters were standardized to six male pups (n=6) each. DEHP was administered in dams via oral gavage during the lactation (post-natal day, PND 1-21) period to three groups (n=3 dams\/group): vehicle, 100 mg\/kg\/day, and 500 mg\/kg\/day. After weaning, the offspring were maintained until adulthood.At PND 90, a total of nine male pups (n=3\/litters\/group) were randomly selected for euthanasia and analyses. At weaning (post-natal day, PND21), animals in the 500DEHP group exhibited reduced body weight and central adiposity, accompanied by increased serum insulin levels, an elevated \u03b2-cell function index (HOMA-\u03b2), and higher serum total triiodothyronine (T3) levels. By adulthood (PND90), the 500DEHP group developed a delayed obesogenic phenotype, characterized by hyperphagia and increased relative visceral white adipose tissue (vWAT) mass. This phenotype was associated with impaired leptin secretion by vWAT, resulting in reduced circulating leptin levels. Consequently, dysregulation of hypothalamic appetite control pathways was observed, marked by decreased expression of the anorexigenic neuropeptide proopiomelanocortin (POMC) and increased expression of the orexigenic neuropeptide neuropeptide Y (NPY), concomitant with reduced suppressor of cytokine signaling 3 (SOCS3) levels. Notably, elevated serum total T3 levels persisted into adulthood. In contrast, in the 100DEHP group, hypothalamic dysfunction appeared to be the primary target, evidenced by a simultaneous increase in both POMC and NPY expression. Collectively, these findings demonstrate that neonatal exposure to DEHP during lactation influences adult phenotype in a dose- dependent manner. Higher-dose exposure (500 mg\/kg\/day) compromises peripheral metabolic homeostasis, particularly through vWAT dysfunction and impaired leptin secretion, whereas lower-dose exposure (100 mg\/kg\/day) preferentially affects central regulation, suggesting dysregulation of hypothalamic neuropeptides.<\/jats:p>","DOI":"10.3389\/fendo.2026.1826776","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:52:56Z","timestamp":1780462376000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal exposure to di-(2-ethylhexyl) phthalate (DEHP) through breastfeeding leads to dysfunction endocrine-metabolic outcomes in male rats at adulthood"],"prefix":"10.3389","volume":"17","author":[{"given":"Thayn\u00e1","family":"Martins Macario","sequence":"first","affiliation":[{"name":"N\u00facleo Multidisciplinar de Pesquisa em Biologia (NUMPEX-Bio), Campus UFRJ - Duque de Caxias Prof. Geraldo Cidade, 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