Effects of maternal PM2.5 exposure during pregnancy on cardiovascular maldevelopment in rat offspring

Epidemiological studies suggest a link between maternal exposure to PM 2.5 during pregnancy and a higher incidence of fetal cardiovascular abnormalities. However, experimental data on the underlying mechanisms remain scarce. This study aims to explore the effects of maternal PM 2.5 exposure during pregnancy on fetal cardiovascular maldevelopment in a rat model. Twenty-eight pregnant rats were divided into control and PM 2.5 -exposed groups according the exposure doses ( N = 7 per group). Rats were administered with PM 2.5 suspensions corresponding to 0, 2.6, 5.5, and 11 μg/d, respectively, during gestation. On gestational day 21, neonatal hearts were collected, and levels of cardiac transcription factors (Tbx2, Tbx20, Hand2 and Gata6), MMP9, TN-C, VEGF-A, NF-κB, apoptotic markers (Bax/Bcl-2 ratio), catalase (CAT), and lipid metabolism indicators were measured. In the 11 μg/d group, the mRNA levels of Tbx2, Tbx20, Hand2, Gata6, MMP9, TN-C and VEGF-A, the protein levels of Tbx2, Hand2, and TN-C, and blood CAT activity were significantly reduced ( P < 0.05). Conversely, NF-κB, Bax/Bcl-2, and serum markers of dyslipidemia (TC, TG, LDH, LDL-C/HDL-C) were significantly elevated ( P < 0.05). Additionally, TN-C and Hand2 mRNA levels were reduced in the 2.6 μg/d group, and LDH level was increased in the 5.5 μg/d group ( P < 0.05). Maternal PM 2.5 exposure during pregnancy is associated with fetal cardiovascular maldevelopments, possibly through the changes of cardiac transcription factors, vascular dysfunction, oxidative stress, apoptosis, and abnormalities of lipid metabolism. • Maternal PM2.5 exposure during pregnancy disrupts fetal cardiac development by suppressing key transcription factors and extracellular matrix regulators. • Maternal PM2.5 exposure triggers oxidative stress, inflammation, and apoptosis, synergistically exacerbating cardiovascular maldevelopment in offspring. • PM2.5 induces lipid metabolism dysregulation, linking environmental pollution to fetal cardiovascular and metabolic dysfunction, and has a long-term "memory effect." • Dose-dependent effects challenge current air quality standards, highlighting vulnerability of fetal development to low-level pollution.