Effects of Di(2-ethylhexyl) phthalate (DEHP) and hyperoxia on cardiovascular development in newborn rats

Background

Preterm infants encounter DEHP through medical devices and equipment. While hyperoxia is known to promote cardiac remodeling and dysfunction, the impact of early phthalate exposure is understudied. We hypothesized that independent and combined DEHP and hyperoxia exposure would impair neonatal cardiovascular development.

Methods

Newborn rats were exposed from birth to day 14 to one of four conditions: control (21% oxygen), hyperoxia (60% oxygen), DEHP (25 mg/m3), and DEHP + hyperoxia (25 mg/m3 DEHP and 60% oxygen). Cardiac tissue and serum were analyzed by histology, RT-qPCR and ELISA for markers of contractility, angiogenesis, and inflammation: myosin heavy chain 6 (Myh6), vascular endothelial growth factor (VEGF), interleukin-4 (IL-4), interleukin-10 (IL-10), and fractalkine (CX3CL1).

Results

Histology found increased cell size, cytoplasm per nucleus, and nuclear area in all exposures. DEHP exposure and hyperoxia exposure reduced Myh6 and VEGF gene expression. Serum VEGF was higher in the DEHP + hyperoxia group compared to hyperoxia alone. IL-10 was decreased in all exposed groups. IL-4 was reduced in the DEHP + hyperoxia group. CXC3L1 was increased in the DEHP + hyperoxia group compared to hyperoxia alone.

Conclusion(s)

Independent and concurrent DEHP and hyperoxia exposure during early neonatal development significantly disrupted markers of cardiac morphology, contractility, angiogenesis, and inflammation.

Impact

Key Message: Postnatal exposure to DEHP adversely impacts neonatal rat cardiovascular development.

Adds to Existing Literature:

This is the first study to examine concurrent long-term hyperoxia and DEHP exposure on cardiovascular development in an animal model relevant to preterm infants.

Identifies a modifiable contributor, DEHP, to adverse cardiovascular development.

Identifies various cardiovascular components affected by DEHP and hyperoxia, including structural, angiogenic, contractile, and inflammatory aspects.

Leads to a new approach to investigate the impact of environmental toxins and the origin of cardiovascular disease in the newborn period.