The roles of hippocampal microRNAs in response to acute postnatal exposure to di(2-ethylhexyl) phthalate in female and male rats

- Female CA3 neuron dendrites are resilient to DEHP-induced effects seen in males.
- DEHP decreases male hippocampal microRNA levels & increases female microRNA levels.
- DEHP lowers miR-132-3p, -191-5p levels in males, but levels increase in females.
- MiR-132-3p, −191-5p have been previously shown to regulate dendrite development.
- DEHP may affect dendrite morphology through sex-specific regulation of microRNAs.

Previous studies have shown that di(2-ethylhexyl) phthalate (DEHP) exposure impairs the normal development of pre- and post-synaptic elements of the male, but not female, rat hippocampus. While males seem to be vulnerable to the neurodevelopmental deficits resulting from DEHP exposure, females appear to show a protective response. The purpose of the present study was to characterize hippocampal microRNAs in female and male rats exposed to DEHP to assess whether any patterns emerged that would be consistent with vulnerability in males and resilience in females. Male and female rats were treated with 0, 1, 10, or 20 mg/kg of DEHP by intraperitoneal injections from postnatal day 16 (PND16) − PND22 and brains were removed and flash frozen on PND78. A group of 85 microRNAs which have been previously shown to play a role in the development and maintenance of hippocampal neurons was assessed with RT-qPCR. In response to DEHP exposure, there were 19 microRNAs that increased in females and 52 that decreased in males. The strongest microRNA response in females occurred in conjunction with the 10 mg/kg of DEHP dose, whereas suppression of microRNAs in males appeared to be dose-dependent. Select hippocampal microRNAs (such as miR-132-3p and miR-191-5p), previously shown to regulate dendrite morphology, were modulated by DEHP exposure in this study. The results suggest that DEHP exposure has the potential to regulate microRNAs in a sex-specific manner which may interfere with proper hippocampal development in males and preserve hippocampal development in females.