ALDH2 Plays a Role in Spermatogenesis and Male Fertility by Regulating Oxidative Stress in Mice

Spermatogenesis and sperm maturation are complex biological processes that involve intricate cellular and molecular interactions. The Aldh2 gene is involved in the metabolism of specific aldehydes generated by oxidative stress. Aldh2 is abundantly expressed in the testis and epididymis; however, the specific role of Aldh2 in regulating spermatogenesis and sperm maturation remains unclear. In the present study, we generated Aldh2 knockout (Aldh2^-/-) mice by using CRISPR/Cas9 technology. Aldh2 gene knockout decreased the fertility of male mice. Compared to the control group mice, Aldh2^-/- mice showed a significant decrease in the thickness of the seminiferous tubules and the number of germ cells. Further investigation revealed that the meiosis of spermatocytes and acrosome formation in sperm were disrupted in Aldh2^-/- mice, leading to oligoasthenoteratozoospermia in male mice. However, the caput epididymis and cauda epididymis in Aldh2^-/- mice showed identical proportions of morphologically abnormal sperm. Mechanistically, 4-hydroxynonenal, 3-nitro-L-tyrosine, and malondialdehyde levels were significantly elevated in both the testis and epididymis of Aldh2^-/- mice, thus indicating increased oxidative stress in the reproductive system. Collectively, our findings demonstrate that Aldh2 plays a critical role in spermatogenesis by regulating oxidative stress in mice.