Cadmium and Reproductive Health in Women: A Systematic Review of the Epidemiologic Evidence

Abstract

An evolving body of evidence supports that cadmium, a non-essential heavy metal, may be associated with multiple adverse women’s reproductive health outcomes. Our objective was to conduct a systematic review of epidemiologic studies that evaluated cadmium exposure and the following reproductive health outcomes: puberty/menarche, fertility, time to pregnancy, pregnancy loss, preeclampsia, endometriosis, uterine leiomyoma, and menopause. Twenty-two studies were identified based upon our search criteria. Available evidence was inadequate to draw meaningful conclusions for most of the reproductive outcomes studied. The strongest evidence was for a possible association between cadmium and preeclampsia, which was limited to cross-sectional studies. Some evidence, although conflicting, was also observed for fertility related outcomes. This lack of evidence underscores the need for additional research on cadmium and women’s reproductive health outcomes.

miRNAs as common regulators of the transforming growth factor (TGF)-β pathway in the preeclamptic placenta and cadmium-treated trophoblasts: Links between the environment, the epigenome and preeclampsia

“…Environmental exposure to toxic metals has been linked to placental toxicity/dysregulation causing improper vascularization in the placenta (Esteban-Vasallo et al 2012; Lazebnik et al 1989; Pollack et al 2014). We have recently demonstrated a significant association between elevated levels of placental cadmium (Cd) and increased odds of developing PE (Laine et al 2015), supporting an existing literature of this relationship (Pollack et al 2014) Exposure to Cd can occur through multiple sources, including contaminated food and contaminated water sources, as well as cigarette smoke (Satarug et al 2010).…”

Cadmium inhibits placental trophoblast cell migration via miRNA regulation of the transforming growth factor beta (TGF-β) pathway

“…Increased levels of cadmium assessed in serum and placental tissue is established to increase the risk of preeclampsia 1, 2 . Additionally, increased expression of members of the TGF- β pathway has been established to be elevated in PE 2, 7, 10, 11, 16 .…”

“…Additionally, increased expression of members of the TGF- β pathway has been established to be elevated in PE 2, 7, 10, 11, 16 . In prior work, we identified a subset of TGF-β pathway-targeting miRNAs that were associated with Cd in the preeclamptic placenta and placental trophoblast cells 7 .…”

“…Previous studies have identified significant associations between exposures to the toxic metal cadmium (Cd) and the development of preeclampsia (PE) 1, 2 . PE is a pregnancy disorder that is characterized by hypertension and proteinuria that can cause adverse health effects for mother and child, and sometimes death 3 .…”

“…PE is a pregnancy disorder that is characterized by hypertension and proteinuria that can cause adverse health effects for mother and child, and sometimes death 3 . The placenta has been identified as the potential etiologic factor in PE development, as well as a target organ for Cd accumulation 2 . Cd exposure can occur through various routes, such as cigarette smoke and ingesting contaminated food from Cd-containing soils 4 .…”