Cadmium reduces growth of male fetuses by impairing development of the placental vasculature and reducing expression of nutrient transporters

Kozlosky, Danielle; Lu, Alexander; Doherty, Cathleen; Buckley, Brian; Goedken, Michael; Miller, Richard K.; Barrett, Emily S.; Aleksunes, Lauren M.

doi:10.1016/j.taap.2023.116636

Cited by 5 publications

(1 citation statement)

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“…It has been observed that cadmium exposure leads to reduction in VEGF levels of human placental trophoblasts [85] and in human umbilical vein endothelial cells (HUVEC) [86]. Several in vivo experiments showed that cadmium exposed pregnant rats have reduced levels of vasculature in placenta, resulting in placental insufficiency [85,87–89]. Alternatively, cadmium exposure has also been seen to cause placental insufficiency by inducing oxidative stress in placenta [90].…”

Section: Resultsmentioning

confidence: 99%

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Sahoo,

Chivukula,

Ramesh

et al. 2023

Preprint

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Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs), using a data-centric approach. By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.

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