Effects of prenatal mobile phone radiation exposure on MMP9 expression: Implications for inflammation, oxidative stress, and sensory-motor impairment after neonatal hypoxia-ischemia in rats.

Due to the widespread use of mobile phones, the biological effects of their non-ionizing radiation are of great interest. Neonatal hypoxia-ischemia (HI), which is characterized by an insufficient supply of oxygen and blood to the brain, is the leading cause of death and brain damage in newborns. Depending on the severity, long-term disabilities such as cerebral palsy, intellectual disability, and cognitive and motor disorders may result. (However, in mild cases, the newborn can develop normally; editor's note.) A lack of oxygen and blood supply to the brain leads to a cascade of events, including inflammation, oxidative stress, and energy failure, which contribute to brain damage. Matrix metalloproteinases (MMPs) play a crucial role in the pathophysiology of neonatal HI. During these events, the upregulation of MMPs can lead to increased permeability of the blood–brain barrier. This allows inflammatory cells and molecules to enter the brain, thereby worsening the condition. This study investigates whether prenatal exposure to mobile phone radiation modulates MMP formation and influences the extent of brain damage.

Twenty pregnant Wistar rats were randomly divided into two groups: a sham exposure group and an exposure group. The exposure source was a 900 MHz mobile phone frequency simulator with a nominal output power of 2 W/kg. The maximum measured power density was 0.45 mW/m² at a distance of 20 cm from the transmitting antenna. The test animals were exposed for 12 hours per day throughout their pregnancies. Immediately after birth, the male offspring were divided into four test groups (n = 20). The groups were labeled as follows: SHAM (surgery without injury to the right carotid artery), EXP (exposure plus surgery without injury to the carotid artery), HI (hypoxia induced by occlusion of the right carotid artery), and HI/EXP (exposure plus hypoxia induced by occlusion of the right carotid artery). Neurobehavioral tests (cliff avoidance and negative geotaxis) were performed 15 days after birth. Then, the brains of the rat pups were removed and analyzed. The scientists evaluated infarct volume, cerebral edema, and the expression of MMP-2 and MMP-9 mRNA (RT-qPCR), as well as TNF-α and the oxidative and antioxidant capacities (TOC/TAC). Statistical analysis was performed using Bonferroni-corrected ANOVA.

There were no significant differences in any of the molecular biological markers (MMPs, TNF-α, and TOC/TAC) between the sham and EXP groups. However, the HI and HI/EXP groups showed statistically significant differences for all markers except MMP-2. Combining HI with exposure was also associated with worse neurobehavioral test results, a larger infarct volume, and greater cerebral edema than HI alone. Infarct size and cerebral edema increased, and performance in behavioral and sensorimotor tests worsened. Animals exposed without HI showed no noticeable changes in this regard.

The data in this publication suggest that prenatal exposure to mobile phone radiation is associated with a poorer prognosis for hypoxic-ischemic encephalopathy. The literature describes how an unphysiological change in MMP-9 expression, as observed here, can result in irreparable neuronal damage [1, 2]. Consistent with the present study's findings, an in vitro study found that mobile phone radiation can modulate MMP expression [3]. The authors hypothesize that exposure to mobile phone radiation in utero, in the context of hypoxic-ischemic encephalopathy, led to increased MMP-9 expression, which then damaged the integrity of the blood–brain barrier. This results in immune cell infiltration, oxidative stress, and pro-inflammatory cytokines, promoting ischemic damage and cerebral edema.

Editor’s note:

The strengths of the work presented include its relevant design with appropriate sample size (prenatal exposure, investigation of the leading cause of neonatal death) and with the investigation of multiple biochemical and morphological endpoints as well as associated neurobehavioral tests. Limitations include an inability to quantify the absorbed dose in the embryo, low measured overall power density, and a lack of long-term data. (RH)

1.         Reinhard S M, Razak K, Ethell IM (2015). A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders. Frontiers in Cellular Neuroscience, 9, 280. https://doi.org/10.3389/fncel.2015.00280

2.         Salah MM, Abdelmawla MA, Eid SR, Hasanin RM, Mostafa EA, Abdelhameed MW (2019). Role of Matrix Metalloproteinase-9 in Neonatal Hypoxic-Ischemic Encephalopathy. Open Access Macedonian Journal of Medical Sciences, 7(13), 2114–2118. https://doi.org/10.3889/oamjms.2019.618

3.         Azimipour F, Zavareh S, Lashkarbolouki T (2020). The effect of radiation emitted by cell phone on the gelatinolytic activity of matrix metalloproteinase-2 and -9 of mouse pre-antral follicles during in vitro culture. Cell Journal, 22(1), 1–8. https://doi.org/10.22074/cellj.2020.6548