Dose‐ and Time‐Dependent Effects of Chlorogenic Acid on Male Reproductive Function in Swiss Mice

Chlorogenic acid (CGA) is a naturally occurring polyphenol found in coffee, as well as in various fruits and vegetables, and is known for its antioxidant and anti-inflammatory properties. However, recent studies suggest that CGA may exhibit dose-dependent biological effects and prooxidant activity. This study aims to investigate the genotoxic impact of CGA on the reproductive organs of mice. Swiss mice were divided into six groups (n = 18). Group 1 received distilled water (control), Group 2 received 15-mg/kg cyclophosphamide (CP) injections (ip). Groups 3-6 were orally administered CGA at 3.75, 7.5, 15, and 30 mg/kg, respectively, for 35 days. On Day 36, blood was collected from nine animals per group for reproductive hormone analysis. The epididymis and testes were excised for a spermiogram, DNA fragmentation analysis, antioxidant analysis, and histopathology. The remaining nine animals were observed for another 35 days posttreatment to evaluate recovery, after which they were sacrificed, and tissues were processed for the same analyses. The result showed that lower doses of CGA elicited more pronounced adverse effects, including increased sperm abnormalities, oxidative imbalance, and DNA fragmentation, particularly after withdrawal. In contrast, the highest dose (30 mg/kg) showed the least alteration with improvements across most parameters and partial recovery postwithdrawal. These findings indicate that the effects of CGA on male reproductive function vary with dose and exposure duration, with lower doses associated with greater adverse outcomes.