Yasrebi Ali, Rojas Catherine M, Anthony Shabree, Feltri Samantha, Evelyn Jamilah, Wiersielis Kimberly, Adams Samantha, Basaly Veronia, Guo Grace L, Aleksunes Lauren M, Roepke Troy A
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Toxics. 2025 Jul 29;13(8):639. doi: 10.3390/toxics13080639.
The maternal-fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood-brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood-brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes.
母胎环境受到多种因素的影响，包括营养和环境污染物，这些因素会影响长期发育。围产期暴露于有机磷酸酯阻燃剂（OPFRs）会破坏能量平衡，并在小鼠中导致适应不良行为。母体肥胖通过损害血脑屏障（BBB）的形成、影响参与能量调节和行为的脑区来影响发育。本研究考察了母体肥胖和围产期OPFR处理对后代发育的综合影响。雌性小鼠分别喂食低脂（LFD）或高脂饮食（HFD）8周，交配后，从妊娠第7天至出生后第14天，用芝麻油或OPFR混合物（磷酸三（1,3-二氯-2-丙基）酯、磷酸三甲苯酯和磷酸三苯酯，各1 mg/kg）进行处理。结果表明，母体饮食和OPFR处理均破坏了新生儿下丘脑的血脑屏障完整性、能量平衡和生殖基因表达。与脂质和外源性物质代谢相关的肝脏基因表达也发生了改变。成年后，LFD OPFR处理的雌性后代表现出增加的回避行为，而HFD OPFR处理的雌性则表现出记忆障碍。代谢评估显示，LFD OPFR处理的雌性能量消耗和夜间活动减少。这些发现表明，母体饮食和OPFR处理会改变新生儿下丘脑和肝脏的基因表达，可能导致长期的代谢和行为变化。
