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Posted by Ted Zava on Thursday, 14 June 2018

Cadmium’s Connection to Infertility and Reproduction

couple.with.fertility.test

Cadmium is a dangerous heavy metal and a known carcinogen. Even though daily exposure is usually relatively low compared to toxins like arsenic, cadmium bioaccumulates with a half-life in the body of 25-30 years.

Essentially, the older you are, the more cadmium you have stored in your body. When cadmium exposure is high, it increases cellular oxidation products that deplete antioxidants like glutathione peroxidase and superoxide dismutase, rendering the body defenseless to further oxidative damage [1].

The most common sources of cadmium exposure are green leafy vegetables and grains, as cadmium is accumulated from contaminated water and soil. Thus, people consuming plant-based diets may be at a higher risk for cadmium exposure. Tobacco, a green leafy plant, concentrates cadmium, which is then highly absorbed through the lungs when smoked, resulting in blood cadmium levels 3 times higher than in non-smokers [2]. In comparison, only a small percentage of cadmium is absorbed in the gut from food. Other sources of cadmium include industrial activities such as smelting and refining, mining, and manufacturing of batteries and cadmium-containing pigments. 

Cadmium and Reproductive Organs

Cadmium is known to accumulate in the liver and kidney (~50% of body burden), but also in reproductive organs such as the testes, ovaries, and placenta [3] [4] [5] [6]. Pregnant women tend to accumulate more cadmium than non-pregnant women, most likely due to reduced iron stores and higher gut absorption [7]. Women who smoke during pregnancy have significantly higher cord blood cadmium levels (placental burden) that correlate to blood cadmium levels [8]. Luckily, cadmium is largely retained in the placenta as it does not effectively cross the placental barrier. On the flip side, cadmium can inhibit zinc, along with other essential elements like copper, calcium, and potassium, from being transported across the placenta [9]. Cadmium accumulation in the testes has been linked to reduced fertility, as shown in studies of male metal workers with lower pregnancy rates and reduced semen quality [10] [11] [12] [13] [14] [15].

Cadmium and Reproductive Hormones

Numerous studies have been published linking cadmium to infertility and complications later in life.

Cadmium directly, and indirectly, influences reproductive hormones. Studies in rodents have shown that cadmium alters levels of testosterone, LH, and FSH, which are all essential for reproduction [16]. Acting as a metalloestrogen, cadmium mimics the growth-promoting actions of estrogens, promoting mammary gland development, inducing early puberty in females, and increasing overall lifetime breast cancer risk [17] [18] [19]. In the context of pregnancy, another study found that a 2-fold increase in placental cadmium was associated with a 50% reduction in placental progesterone [20].

Cadmium's Effect on the Fetus and Infant

Numerous studies have been published linking cadmium to infertility and complications later in life. Lower birthweight, reduced cognitive ability, epigenetic modifications, and increased chances of a miscarriage have all been associated with cadmium exposure [21] [22] [23]. Post-delivery, a newborn can be exposed to cadmium from second-hand smoke, infant formula, and breast milk. 

The Zinc/Cadmium Connection

Cadmium’s [Cd2+] primary antagonist in the body is zinc [Zn2+] due to similar electron configurations. Cadmium disrupts zinc homeostasis, whereas zinc protects against cadmium toxicity [24] [25]. Zinc is essential for ovulation, egg fertilization, and the development and maturation of spermatozoa, along with many non-reproductive processes in the body [26]. One of zinc’s protective mechanisms is to stimulate metallothionein production (a zinc storage protein) which binds tightly to heavy metals like cadmium to prevent oxidative stress. With regard to reproductive function, zinc is essential for ovulation, egg fertilization, and the development and maturation of spermatozoa, along with many non-reproductive processes in the body [26]. Increased zinc supplementation was shown to prevent testicular toxicity and maintain testosterone production during cadmium-induced prostate cancer in rats [27]. It may have similar protective actions in humans. Zinc also helps prevent cadmium from disturbing bone metabolism, a result of the displacement of calcium (Ca2+) which has a similar atomic radius [28].

What Can You Do to Protect Against, Detect, or Prevent Cadmium Exposure?

  • Test for recent (whole blood) and past (urine) cadmium exposure
  • Refrain from smoking cigarettes or any other tobacco-containing product
  • Test garden soil for cadmium (and other toxic elements like lead)
  • Eat a varied diet high in antioxidants and essential elements (zinc/calcium/selenium/magnesium/iron are all very important)
  • Minimize exposure when working with commercial products (e.g., pigments) containing cadmium

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References 

[1]  Sen Gupta R, et al. Vitamin C and vitamin E protect the rat testes from cadmium-induced reactive oxygen species. Mol Cells. 2004;17:132-9.

[2]  Toxicological Profile for Cadmium (Final Report). In: Registry AfTSaD, ed. Atlanta: ASTDR; 1999.

[3]  Järup L, et al. Health effects of cadmium exposure--a review of the literature and a risk estimate. Scand J Work Environ Health. 1998;24 Suppl 1:1-51.

[4]  Varga B, et al. Age dependent accumulation of cadmium in the human ovary. Reprod Toxicol. 1993;7:225-8.

[5]  Piasek M, et al. Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol. 2001;15:673-81.

[6]  Paksy K, et al. Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells. J Appl Toxicol. 1997;17:321-7.

[7]  Nishijo M, et al. The gender differences in health effects of environmental cadmium exposure and potential mechanisms. Mol Cell Biochem. 2004;255:87-92.

[8]  Galicia-García V, et al. Cadmium levels in maternal, cord and newborn blood in Mexico City. Toxicol Lett. 1997;91:57-61.

[9]  Kuriwaki J, et al. Effects of cadmium exposure during pregnancy on trace elements in fetal rat liver and kidney. Toxicol Lett. 2005;156:369-76.

[10]  Robins TG, et al. Semen quality and fertility of men employed in a South African lead acid battery plant. Am J Ind Med. 1997;32:369-76.

[11]  Bonde JP. The risk of male subfecundity attributable to welding of metals. Studies of semen quality, infertility, fertility, adverse pregnancy outcome and childhood malignancy. Int J Androl. 1993;16 Suppl 1:1-29.

[12]   Gennart JP, et al. Fertility of male workers exposed to cadmium, lead, or manganese. Am J Epidemiol. 1992;135:1208-19.

[13]   Chia SE, et al. Blood cadmium levels in non-occupationally exposed adult subjects in Singapore. Sci Total Environ. 1994;145:119-23.

[14]   Akinloye O, et al. Cadmium toxicity: a possible cause of male infertility in Nigeria. Reprod Biol. 2006;6:17-30.

[15]  Benoff S, et al. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000;6:107-21.

[16]  Lafuente A, et al. Cadmium exposure differentially modifies the circadian patterns of norepinephrine at the median eminence and plasma LH, FSH and testosterone levels. Toxicol Lett. 2004;146:175-82.

[17]  Johnson MD, et al. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med. 2003;9:1081-4.

[18]   Stoica A, et al. Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol. 2000;14:545-53.

[19]  Lin J, et al. Dietary intake and urinary level of cadmium and breast cancer risk: A meta-analysis. Cancer Epidemiol. 2016;42:101-7.

[20]  Piasek M, et al. Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol. 2001;15:673-81.

[21]  Luo Y, et al. Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight. BMC Public Health. 2017;17:354.

[22]  Sanders AP, et al. Perinatal and Childhood Exposure to Cadmium, Manganese, and Metal Mixtures and Effects on Cognition and Behavior: A Review of Recent Literature. Curr Environ Health Rep. 2015;2:284-94.

[23]   Appleton AA, et al. Prenatal exposure to neurotoxic metals is associated with increased placental glucocorticoid receptor DNA methylation. Epigenetics. 2017;12:607-615.

[24]  Brzóska MM, et al. Interactions between cadmium and zinc in the organism. Food Chem Toxicol. 2001;39:967-80.

[25]  Brzóska MM, et al. Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology. 2007;237:89-103.

[26]  Favier AE. The role of zinc in reproduction. Hormonal mechanisms. Biol Trace Elem Res. 1992;32:363-82.

[27]  Waalkes MP, et al. Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site. Cancer Res. 1989;49:4282-8.

[28]  Brzóska MM, et al. Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology. 2007;237:89-103.

Tagged in: Dried Urine Testing Fertility Cadmium Heavy Metals