# Pyrroloquinoline Quinone Alleviates Tris(1,3-Dichloro-2-Propyl) Phosphate-Induced Damage During Mouse Oocyte Maturation

## TL;DR

This study shows that a fire retardant harms mouse egg development, but a natural antioxidant can protect against this damage.

## Contribution

The study identifies pyrroloquinoline quinone as a potential protective agent against fire-retardant-induced oocyte damage.

## Key findings

- TDCIPP exposure impairs mouse oocyte maturation by inducing oxidative stress and mitochondrial dysfunction.
- PQQ supplementation reverses TDCIPP-induced damage by reducing ROS and preserving mitochondrial function.
- PQQ inhibits apoptosis triggered by TDCIPP through modulation of Bcl-2 and Bax expression.

## Abstract

Tris(1,3-dichloro-2-propyl) phosphate is a common chemical used to prevent fires that is frequently found in our homes and environment. Recent concerns suggest it may harm reproductive health. Our study aimed to investigate how this fire-retardant chemical affects the development of mouse oocytes and whether a natural protective substance called pyrroloquinoline quinone can reduce this damage. We discovered that the fire retardant significantly hinders the ability of oocytes to develop and prepare for fertilization. It does this by increasing harmful oxygen molecules, damaging the tiny powerhouses that provide energy to the cell, and triggering a process of cell death. Importantly, our results showed that adding the natural protective substance successfully prevented these problems, allowing the oocytes to develop normally and stay healthy. In conclusion, this research demonstrates that while environmental pollutants like fire retardants can damage fertility, natural substances can offer a potential shield. These findings are important for society as they help us understand the risks posed by everyday chemicals and suggest new ways to protect the reproductive health of both humans and animals from environmental threats.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a ubiquitous organophosphate flame retardant posing potential threats to reproductive health. Given that TDCIPP toxicity is often linked to oxidative stress, pyrroloquinoline quinone (PQQ), a potent natural antioxidant and mitochondrial nutrient, was hypothesized to mitigate these adverse effects. This study investigated the impact of TDCIPP exposure on the in vitro maturation of mouse oocytes and evaluated the protective role of PQQ. Using an in vitro maturation model, we assessed the toxic effects of TDCIPP by examining the first polar body extrusion (PBE) rate and cumulus expansion, followed by analyses of oxidative stress (ROS and GSH), mitochondrial integrity (ATP content and distribution), and apoptosis-related markers through transcriptome sequencing (Smart RNA-seq), quantitative real-time PCR, and immunofluorescence. The results demonstrated that TDCIPP significantly suppressed cumulus expansion and reduced the PBE rate. Mechanistically, TDCIPP induced severe oxidative stress, disrupted mitochondrial function, and activated the apoptotic pathway. Furthermore, TDCIPP triggered early apoptotic signaling by downregulating Bcl-2 and upregulating Bax. Notably, supplementation with PQQ effectively reversed these detrimental effects by reducing intracellular ROS levels, maintaining GSH content, preserving mitochondrial density and ATP production, and inhibiting apoptosis. In conclusion, our findings provide new insights into the gamete toxicity of TDCIPP and suggest that PQQ may serve as a potential therapeutic agent to protect oocyte quality against environmental pollutant-induced damage.