Male infertility is a growing reproductive health concern worldwide. While genetic, hormonal, and reproductive tract disorders are well-recognized causes, environmental exposure and lifestyle-related factors are attracting increasing attention. Some pharmaceutical residues and environmental pollutants may enter the human body through water, soil, or the food chain, but their potential effects on male reproductive health remain incompletely understood.
A new study published in Science China Life Sciences investigated how ornidazole, an antimicrobial drug used in humans, livestock, and aquaculture, may affect male fertility.
The researchers first analyzed serum samples and found that serum ornidazole levels were higher in patients with oligozoospermia than in healthy controls. Higher serum ornidazole levels were also negatively associated with sperm concentration and total normal-progressively motile sperm count, suggesting a possible link between ornidazole-related exposure and reduced sperm quality.
To further explore this association, the team used mouse and cell models and found that ornidazole exposure reduced sperm count and motility, disrupted seminiferous tubule structure, and interfered with meiotic progression. Mechanistically, ornidazole increased the expression of voltage-dependent anion channel 1 (VDAC1), a key protein located at mitochondria-associated endoplasmic reticulum membranes (MAMs). This disrupted MAM balance, promoted mitochondrial calcium overload, impaired mitochondrial function, and triggered oxidative stress.
The researchers also investigated the potential protective effect of DHA, an omega-3 fatty acid found in dietary sources such as fish oil and algal oil. In the mouse model, DHA supplementation significantly improved ornidazole-induced spermatogenic defects. Notably, DHA is readily available to the general public and has a favorable biosafety profile. These features make it a promising therapeutic metabolite for oligoasthenozoospermia induced by environmental pollution.
Bing Yao, Jun Jing, and Xie Ge from the Department of Reproductive Medicine, Jinling Hospital Affiliated to Nanjing University, and Yong Wang from Medical School of Nanjing University are the co-corresponding authors. Chuwei Li, Shanmeizi Zhao, Chongli Shi, and Shanshan Sun contributed equally as co-first authors.
Science China Life Sciences