Functional and metabolic changes to male reproductive cells after exposure to common herbal medicines

Tayler C Kent

Herbal medicines and dietary supplements are used by around 63% of Australians, despite known risks to consumers. In Australia, these products are deemed ‘low risk’, and as such their regulation by the Therapeutic Goods Administration (TGA) is largely hands-off compared to registered medicines, resulting in widespread use despite a lack of safety and efficacy data. Particularly common are ‘fertility-boosting’ supplements, which are heavily marketed towards and have a vulnerable audience in couples trying to conceive. In addition, the use of these supplements has more recently expanded into veterinary assisted reproduction, especially as an additive to frozen spermatozoa, for their purported antioxidant effects. Using ram spermatozoa as a model for both human and veterinary applications, this study characterised the biochemical changes in spermatozoa after exposure to three common herbal supplement ingredients: Panax ginseng (ginseng), Lepidium meyenii (maca) root and Camellia sinensis (green tea) extract (GTE). A suite of techniques including flow cytometry, gas chromatography-mass spectrometry, computer-assisted sperm analysis (CASA) and enzyme-linked immunosorbent assay (ELISA) was used to demonstrate that exposure to varying concentrations of these compounds induced significant biochemical changes in spermatozoa. These included altered energy metabolism and cell signalling pathways, as well as increased frequency of acrosome reaction, an increase in mitochondrial oxidative stress, and increased DNA fragmentation. Additionally, isolated active ginsenosides and catechins (from ginseng and GTE respectively) were found to induce changes similar to the parent compounds when spermatozoa were exposed. The effect of herbal compounds on cultured testicular cell metabolism was also investigated. Murine Leydig and Sertoli cells were exposed to the compounds listed above, and select biochemical changes measured. Testicular cells also exhibited altered energy metabolism, cell signalling, and hormone changes in the presence of these supplements. Despite the reported antioxidant activity of these compounds, the increase in mitochondrial reactive oxygen species (ROS) production and DNA damage in spermatozoa indicates that, at the concentrations tested, these compounds had a pro-oxidant effect on spermatozoa, which may lead to decreased fertility. Significant DNA damage, caused by oxidative stress, can reduce the capacity of a spermatozoon to fertilise an ovum or compromise the integrity of a zygote if fertilisation does occur. Additionally, the increase in spontaneous acrosome reaction, normally the final step in fertilisation, as well as increased oestrogen concentration in testicular cells, suggest that these compounds may act as endocrine disruptors and alter normal reproductive function. These results indicate that herbal medicines and dietary supplements containing ginseng, maca or GTE should be used with caution until their effects on male fertility are further elucidated. Future research in this area should target the mechanism by which these compounds induce DNA damage and endocrine disruption.

Functional and metabolic changes to male reproductive cells after exposure to common herbal medicines

Files and links (1)

Abstract

Details

UN Sustainable Development Goals (SDGs)

Metrics