Trace Element Dyshomeostasis as a Mediator of Toxic Metal-Induced Reproductive Dysfunction: Mechanistic Insights and...

Exposure to toxic metals has become a major environmental and public health concern due to its adverse effects on reproductive health. Recent evidence indicates that, beyond their direct toxicity, toxic metals can disrupt the homeostasis of essential trace elements that are critical for maintaining normal reproductive function. This review aims to examine the role of toxic metal-induced trace element imbalance in reproductive dysfunction and to elucidate the underlying mechanisms linking metal exposure to impaired fertility.

Relevant experimental, epidemiological, and clinical studies investigating the effects of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and chromium (Cr) on reproductive health were comprehensively evaluated. We conducted a structured narrative literature search of PubMed, Scopus, Web of Science, and Google Scholar for relevant publications published between 2000 and March 2025. The study included original research articles, systematic reviews and meta-analyses investigating toxic metal induced reproductive dysfunction and trace elements dysregulation in the body.

Current evidence demonstrates that toxic metals interfere with the absorption, transport, distribution, and biological functions of essential trace elements by competing for transporters, binding proteins, and intracellular targets. Cd, Pb, Hg, As, and Cr are considered as the most frequently studied environmental toxic metals in association with reproductive impairment. Combinedly these metals disturb the homeostasis of important trace elements and interfere with reproductive functions by several convergent pathways such as induction of oxidative stress and dysfunction of mitochondrial, endocrine impairment, inflammation, induction of apoptosis and DNA damage, epigenetic modulation, and etc.In males, toxic metal exposure is associated with impaired testicular development, altered steroidogenesis, reduced sperm quality, decreased sperm motility, and compromised fertility. In females, it contributes to ovarian dysfunction, menstrual irregularities, implantation failure, pregnancy complications, and adverse fetal outcomes. Among the affected trace elements, zinc and selenium play particularly important protective roles through their involvement in antioxidant defense, genomic stability, mitochondrial function, and endocrine regulation.

Trace element Dyshomeostasis represents a central mechanism linking toxic metal exposure to reproductive impairment. Present evidence indicates the similarity of mechanism of reproductive physiology modulation by cadmium, lead, mercury, arsenic and chromium involving oxidative stress, interfering hormonal axis, impairing mitochondria functions, inflammation, apoptosis and changing trace element metabolism. Detailed knowledge about this common process needs to enable efficient prevention strategies and effective treatments.