Rat embryos cultured under copper‐deficient conditions develop abnormally and are characterized by an impaired oxidant defense system

Hawk, Susan N.; Uriu‐Hare, Janet Y.; Daston, George P.; Jankowski, Margaret A.; Kwik‐Uribe, Catherine; Rucker, Robert B.; Keen, Carl L.

doi:10.1002/(sici)1096-9926(199806)57:6<310::aid-tera4>3.0.co;2-#

Cited by 37 publications

(26 citation statements)

References 46 publications

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“…The results were consistent with induction of Mn-based SOD activity, also associated with reduced FF ROS, and greater oocyte competence [14,15,41,44]. Similarly, higher FF Cu-Zn SOD is associated with an optimized follicular environment via reduced ROS [45]; a study of rat dams fed a Cu-deficient diet (<0.5 μg Cu/g) had decreased embryo quality compared to those fed a Cu-sufficient diet (8.0 μg Cu/g) [46]. However, a Japanese study of 41 oocytes reported no associations for 40 essential elements measured in human FF and fertilization or embryo quality [47].…”

Section: Discussionmentioning

confidence: 65%

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

Ingle

Bloom

Parsons

et al. 2016

J Assist Reprod Genet

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Purpose A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. Methods We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking.Results Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. Conclusions Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

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Section: Discussionmentioning

confidence: 65%

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

Ingle

Bloom

Parsons

et al. 2016

J Assist Reprod Genet

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“…A deficit of copper (Cu) during pregnancy and early postnatal period can lead to intrauterine death, a high incidence of structural and functional abnormalities in the embryo and fetus, and long‐lasting adverse functional effects on the offspring [2, 62–71].…”

Section: Copper Deficiency and Pregnancy Outcomementioning

confidence: 99%

“…The whole embryo culture (WEC) model allows one to control the culture conditions, thus it is a valuable tool in the field of developmental biology to study mechanisms involved in teratogenesis [148]. Using WEC, we have shown that embryos from Cu deficient rat and mouse dams cultured in Cu deficient serum have a high frequency of brain, vessel, and cardiac defects [62–64, 121, 149]. Cu deficiency can reduce the activities of a number of oxidant defense enzymes including non‐Cu binding proteins such as selenium‐dependent glutathione peroxidase and catalase [150].…”

Section: Potential Mechanismsmentioning

confidence: 99%

“…Cu deficiency can reduce the activities of a number of oxidant defense enzymes including non‐Cu binding proteins such as selenium‐dependent glutathione peroxidase and catalase [150]. As observed in adult animals, Cu deficiency in the embryo reduces the activity of the oxidant defense enzyme, CuZn‐SOD, leading to increased superoxide anion concentrations [62–64, 121, 149]. Cu deficient embryos tended to have higher 8‐hydroxy‐2′‐deoxyguanosine concentrations than controls, indicating increased DNA damage [149].…”

Section: Potential Mechanismsmentioning

confidence: 99%

“…One consequence of a decrease in CuZn‐SOD activity in embryos and subsequent increase in the formation of superoxide anion levels [63, 64, 149] is that the superoxide anions can react rapidly with NO to form peroxynitrite (ONOO − ), a strong oxidant that can lead to protein nitration [152] (Fig. 1).…”

Section: Potential Mechanismsmentioning

confidence: 99%

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Influence of copper on early development: Prenatal and postnatal considerations

et al. 2010

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Copper (Cu) is an essential nutrient whose requirement is increased during pregnancy and lactation. These represent times of critical growth and development, and the fetus and neonate are particularly vulnerable to deficiencies of this nutrient. Genetic mutations that predispose the offspring to inadequate stores of Cu can be life threatening as is observed in children with Menkes disease. During the last decade, severe Cu deficiency, once thought to be a rare condition, has been reported in the literature at an increasing frequency. Secondary Cu deficiencies can be induced by a variety of ways such as excessive zinc or iron intake, certain drugs, and bariatric surgery. Premature and low birth weight infants can be born with low Cu stores. A number of mechanisms can contribute to the teratogenicity of Cu including decreased activity of select cuproenzymes, increased oxidative stress, decreased nitric oxide availability, altered iron metabolism, abnormal extracellular matrix protein crosslinking, decreased angiogenesis and altered cell signaling among others. The brain, heart, and vessels as well as tissues such as lung, skin and hair, and systems including the skeletal, immune, and blood systems, are negatively affected by suboptimal Cu during development. Additionally, persistent structural, biochemical, and functional adverse effects in the offspring are noted even when Cu supplementation is initiated after birth, supporting the concept that adequate Cu nutriture during pregnancy and lactation is critical for normal development. Although Cu-containing IUDs are an effective method for increasing intrauterine Cu concentrations and for reducing the risk of pregnancy, high amounts of dietary Cu are not thought to represent a direct developmental risk.

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Mutagenicity, Carcinogenicity, and Teratogenicity

Gebhart¹

2004

Elements and Their Compounds in the Environment

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Rat embryos cultured under copper‐deficient conditions develop abnormally and are characterized by an impaired oxidant defense system

Cited by 37 publications

References 46 publications

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

Influence of copper on early development: Prenatal and postnatal considerations

Mutagenicity, Carcinogenicity, and Teratogenicity

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