Maternal Exposure to Polystyrene Nanoplastics Disrupts Spermatogenesis in Mouse Offspring by Inducing <i>Prdm14</i> Overexpression in Undifferentiated Spermatogonia.

Abstract

Undifferentiated spermatogonia (Undiff-SPG) plays a critical role in maintaining continual spermatogenesis. However, the toxic effects and molecular mechanisms of maternal exposure to nanoplastics on offspring Undiff-SPG remain elusive. Here, we utilized a multiomics combined cytomorphological approach to explore the reproductive toxicity and mechanisms of polystyrene nanoplastics (PS-NPs) on offspring Undiff-SPG in mice after maternal exposure. The results indicated that PS-NPs decreased testosterone levels and reduced sperm concentration and quality in offspring male mice through maternal exposure. Moreover, PS-NPs could enter offspring Undiff-SPG, increase ROS levels, and decrease the viability of Undiff-SPG. According to the transcriptomics and proteomics analyses, PS-NPs caused offspring male mice Undiff-SPG inflammation by increasing the expression of <i>Tnfsf18</i>/<i>Nlrp6</i>. Mechanistically, we found that inflammation induced overexpression of the transcription factor <i>Prdm14</i> in Undiff-SPG, which suppressed the expression of <i>Ccdc33</i> and <i>Tcirg1</i>. Additionally, PS-NPs disrupted offspring spermatogenesis by inhibiting the <i>Osbp2</i>/<i>Zcwpw1</i>/<i>Dhps</i> expression. Furthermore, PS-NPs reduced the Undiff-SPG autophagic flux by reducing the expression of <i>Igbp1</i>/<i>Gabarapl2</i>. In conclusion, maternal exposure to PS-NPs caused inflammation in offspring Undiff-SPG, which resulted in <i>Prdm14</i> overexpression that could disrupt spermatogenesis and normal autophagy.