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Stella Tommasi, Tevfik H. Kitapci, Hannah Blumenfeld, and Ahmad Besaratinia (Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA)
Human exposure to secondhand smoke (SHS) is known to result in adverse effects in multiple organ systems. However, the impact of SHS on the male reproductive system, particularly on the regulation of genes and pathways that govern sperm production, maturation, and functions remains understudied. Here, we demonstrate that sub-chronic exposure of mice to SHS alters the expression of genes involved in signaling pathways that modulate testis development and function. Preferential targeting of lncRNAs in the testis of SHS-exposed mice is especially significant considering their crucial role in the spatial and temporal modulation of spermatogenesis. Equally important is the discovery of a novel frameshift variant that is unique to SHS-exposed mice and is generated by retention of a short intron within Pde1a, a key regulator of spermatogenesis. Intron retention is a form of alternative splicing that has been recognized as an important regulatory mechanism to fine-tune gene expression. The novel variant identified in this study is likely to represent a safeguard mechanism to regulate transcription of Pde1a and preserve normal testis function during harmful exposure to environmental agents.