The Effects of Toxic Heavy Metals Lead, Cadmium and Copper on the Epidemiology of Male and Female Infertility Original paper

What was reviewed?

This review comprehensively evaluated the effects of toxic heavy metals on the epidemiology of male and female infertility. The authors systematically searched and synthesized findings from articles published between 1982 and 2021 in databases such as PubMed, Google Scholar, Scopus, and others, focusing on the mechanistic and epidemiological associations between these metals and reproductive dysfunction. The review explores the multifaceted ways that heavy metal exposure, both environmental and occupational, influences reproductive health, including hormonal disruption, impaired gametogenesis, and direct damage to reproductive tissues. Special attention is given to the biochemical mechanisms by which these metals exert toxic effects, such as oxidative stress, enzyme inhibition, and endocrine disruption, all of which are highly relevant to clinicians concerned with environmental determinants of infertility.

Who was reviewed?

The review encompasses a broad range of human and animal studies, including epidemiological research on general populations and occupational groups, as well as controlled laboratory investigations in animal models. Human studies included both men and women from diverse geographic and occupational backgrounds, such as industrial workers, smokers, and populations with high environmental exposure. Animal research provided mechanistic insights, particularly regarding gamete quality, hormonal changes, and reproductive organ pathology following heavy metal exposure. Some studies included in the review also examined the reproductive health of non-human species to elucidate underlying biological processes and to support observed epidemiological trends in humans.

Most important findings

The review identifies strong associations between exposure to lead, cadmium, and copper and increased risk of infertility in both sexes. Cadmium, widely distributed in the environment, is linked to direct damage to the ovaries and testes, reduced sperm count, motility, and viability, as well as impaired oocyte maturation. It acts as a reproductive toxin by replacing zinc in enzymes and altering protein function, leading to oxidative stress and cytotoxicity. Lead exposure disrupts hormonal balance by interfering with calcium-mediated cellular activities and is associated with decreased sperm quality, impaired oocyte development, increased risk of miscarriage, and stunted fetal growth. Occupational and environmental exposures, such as working in lead mines or exposure to cigarette smoke, exacerbate these effects. Elevated copper levels, while copper is essential in trace amounts, are correlated with oxidative damage and sperm dysfunction at higher concentrations. The review highlights the impact of heavy metals on key microbiome-modulated processes (e.g., oxidative stress, inflammation) and notes that heavy metal exposure may alter the host’s microbiome, which can further influence reproductive health outcomes.

Key implications

Clinicians should be aware of the significant impact that environmental and occupational exposures to lead, cadmium, and copper can have on reproductive health. The review supports incorporating environmental exposure histories into infertility assessments, particularly for patients with unexplained infertility or those with relevant occupational risks. The evidence also suggests that heavy metal-induced oxidative stress and endocrine disruption might be compounded or modulated by changes in the reproductive tract microbiome, indicating a potential avenue for future diagnostic and therapeutic interventions. Surveillance of heavy metal exposure, coupled with targeted interventions to reduce environmental risk, could improve fertility outcomes and inform public health strategies. Furthermore, the recognition of microbiome–heavy metal interactions opens the door to novel research on microbial biomarkers and microbiota-targeted therapies in infertility management.