The effects of postnatal exposure to di-n-butyl phthalate (DBP) on the male reproductive system in animals: A systematic review and meta-analysis

Di-n-butyl phthalate (DBP) is a ubiquitous environmental contaminant widely used in personal care products and medical products, causing male reproductive toxicity in humans and animals following exposure. It has endocrine-disruptive activities, causing adverse effects on the male reproductive system. This study aimed to investigate the male reproductive injury induced by DBP in animals. We conducted a systematic review and meta-analysis of the related literature captured in Google Scholar, MEDLINE, Scopus, PubMed and Web of Sciences databases. This review included animal studies that were postnatally exposed to DBP. After applying the inclusion and exclusion criteria, a total of 48 relevant studies were selected, which included studies in rats (n = 29), mice (n = 5), rabbits (n = 3), birds (n = 6), and fish (n = 5) exposed to DBP. The scope of the study included testicular and epididymal morphology, sperm quality and oxidative stress parameters, steroidogenic enzymes, and sex steroid hormones. The meta-analysis focused on rat studies, which revealed a significant decrease in sperm count (p < 0.001), sperm motility (p < 0.001), superoxide dismutase (SOD, p < 0.001) activity and testosterone (p < 0.001) concentration. Moreover, DBP exposure significantly increased sperm abnormality (p < 0.001), catalase (CAT; p = 0.003) activity and malondialdehyde (MDA; p < 0.001) levels. Postnatal exposure to 1 mg/kg DBP could decrease the sperm count, sperm motility, testosterone concentration, and SOD activity by 5.87 %, 0.17, 7.46 % and 21.38 %, respectively. As a result of the meta-analysis, SOD activity was more sensitive to DBP following postnatal exposure than CAT activity or MDA levels, while sperm abnormality was less susceptible than sperm count and sperm motility to DBP exposure. Generally, the systematic review and meta-analysis demonstrated that postnatal exposure to DBP-induced male reproductive injury by inducing oxidative stress and altering steroidogenesis, and sex hormones in animals. Moreover, the review identified important gaps in animal studies of dermal exposure to DBP, emphasizing the need for further research to assist in conducting more rigorous epidemiological and risk assessment studies that represent real-life exposure scenarios.