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The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST).
Jenkins, T, Aston, K, Carrell, D, DeVilbiss, E, Sjaarda, L, Perkins, N, Mills, JL, Chen, Z, Sparks, A, Clemons, T, et al
Fertility and sterility. 2022;(1):75-85
Abstract
OBJECTIVE To determine if 6-month folic acid (5 mg) and zinc (30 mg) supplementation impacts sperm DNA methylation patterns. DESIGN A multicenter, double-blind, block randomized, placebo-controlled trial titled "The Folic Acid and Zinc Supplementation Trial (FAZST)." SETTING Infertility care centers. PATIENT(S): Male partners (18 years and older) from heterosexual couples (female partners aged 18-45 years) seeking fertility treatment were recruited. INTERVENTION(S): Men were randomized 1:1 to receive folic acid (5 mg) and elemental zinc (30 mg) (n = 713) or a matching placebo (n = 757) daily for 6 months. MAIN OUTCOME MEASURE(S): Sperm DNA methylation was analyzed using the EPIC methylation array (Illumina) at 6 months. Differential sperm DNA methylation was assessed at multiple levels (regional, single cytosine phosphate guanine, etc.). We additionally assessed the impact of supplementation on epigenetic age. RESULT(S): No significant differences were identified between the treatment and placebo groups although some trends appeared to be present. To determine if these trends were noteworthy, we implemented various permutations and found that the patterns we identified were no more than would be expected by random chance. CONCLUSION(S): The data presented here strongly suggest that this supplementation regimen is not effective at altering sperm DNA methylation. These data comport well with previous findings from the FAZST study that found no impact of supplementation on basic semen analysis parameters or live birth. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT01857310.
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A Randomized Trial to Evaluate the Effects of Folic Acid and Zinc Supplementation on Male Fertility and Livebirth: Design and Baseline Characteristics.
Schisterman, EF, Clemons, T, Peterson, CM, Johnstone, E, Hammoud, AO, Lamb, D, Carrell, DT, Perkins, NJ, Sjaarda, LA, Van Voorhis, BJ, et al
American journal of epidemiology. 2020;(1):8-26
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Abstract
The Folic Acid and Zinc Supplementation Trial (FAZST) was a multicenter, double-blind, block-randomized, placebo-controlled trial to determine whether folic acid and zinc supplementation in men improves semen quality and increases livebirth rate among couples seeking infertility treatment (2013-2017). Eligible men were aged 18 years or older with female partners aged 18-45 years, seeking infertility treatment. Men were randomized (1:1) to 5 mg folic acid and 30 mg elemental zinc daily or matching placebo for 6 months. Randomization was stratified by site and intended infertility treatment (in vitro fertilization (IVF), non-IVF/study site, and non-IVF/outside clinic). Follow-up of men continued for 6 months, and female partners were passively followed for a minimum of 9 months. Women who conceived were followed throughout pregnancy. Overall, 2,370 men were randomized during 2013-2017 (1,185 folic acid and zinc, 1,185 placebo); they had a mean age of 33 years and body mass index (weight (kg)/height (m)2) of 29.8. Most participants were white (82%), well educated (83% with some college), and employed (72%). Participant characteristics were balanced across intervention arms. Study visits were completed by 89%, 77%, and 75% of men at months 2, 4, and 6, respectively. Here we describe the study design, recruitment, data collection, lessons learned, and baseline participant characteristics.
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Research on Root Responses to Pb and Zn Combined Stress of Carex putuoshan.
Hu, YL, Tan, JL, Wang, CL, Yang, ZB, Yang, YX, Chen, Z, Lin, LJ, Wang, YJ, Sun, G, Zhu, XM, et al
Protein and peptide letters. 2016;(5):478-87
Abstract
Pb hyper-accumulated Carex putuoshan was taken as experimental material and subjected to combined stress of Pb and Zn. The differential expression of proteins in their roots were analyzed by Proteomic Approach. The protein that was directly involved in the cellular defense under the Pb and Zn combined stress was separated, and expression of those genes was analyzed with Carex Evergold as control. The results were obtained by MALDI-TOF/MS analysis. After applying Pb and Zn combined stress, the expression of 9 protein spots (including 7 different proteins, 2 identical proteins, 1 unknown protein) in Carex putuoshan root was found to be significantly up-regulated. Five proteins were obtained from the 9 proteins related to carbohydrate metabolism, including malate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, frutose-1,6-bisphosphate aldolase, enolase, and 6- phosphogluconate dehydrogenase. Two proteins were related to protein biosynthesis, including isoflavone reductase and phytochelatin synthase (PCS). From these proteins, the most important protein is PCS, which is a key enzyme in the synthesis of phytochelatins (PCs) and plays an important role in chelation. It is directly involved in cellular defense under Pb and Zn stress. After Pb and Zn combined stress, the CpPCS in Carex putuoshan was cloned. The full length of cDNA is 1461 bps, and it encodes 486 amino acids with molecular weight of 53.86 kD and pI value of 6.12. Two typical phytochelatin synthase subfamily domains constitute CpPCS protein, which includes three adjacent Cys-Cys elements in the C-terminal region. Phylogenetic analysis of PCS proteins from different species showed that it had the closest relationship with the Oryza sativa and Triticum aestivum. Real-time quantitative PCR analysis indicated that CpPCS and CePCS (Carex Evergold) genes were expressed in the root. The CpPCS and CePCS genes were up-regulated by Pb and Zn treatments. The expression of CpPCS was higher than that of CePCS under the same condition. The study found that CpPCS expression was increased by Pb and Zn stress in the Carex putuoshan enrichment process of Pb, which lead to high expression of PCS protein. CpPCS improved the accumulation ability and resistance of Carex putuoshan to heavy metals with the expression level of glucose metabolism related proteins increasing after Pb and Zn stress.
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Iron supplementation does not affect copper and zinc absorption in breastfed infants.
Domellöf, M, Hernell, O, Abrams, SA, Chen, Z, Lönnerdal, B
The American journal of clinical nutrition. 2009;(1):185-90
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Abstract
BACKGROUND Iron supplements are commonly recommended for infants but were suggested to inhibit zinc and copper absorption. OBJECTIVE The objective of this study was to investigate potential effects of iron supplementation, infant age, and mineral status on zinc and copper absorption in infants at 6 and 9 mo of age. DESIGN Twenty-five healthy breastfed term infants were recruited from a larger randomized iron supplementation trial. Six of these infants received iron supplements (1 mg . kg(-1) . d(-1)) from 4 to 9 mo, 8 were supplemented from 6 to 9 mo, and 11 received placebo only. Zinc and copper absorption was measured at 6 and 9 mo of age, using orally administered (70)Zn and (65)Cu and fecal monitoring of recovered stable isotopes. RESULTS Mean (+/-SD) zinc absorption was 51.9 +/- 17.9%, and mean copper absorption was 79.0 +/- 13.5%. No significant difference was observed in zinc or copper absorption between 6 and 9 mo of age. When combining all measurements, no significant effect of prior iron supplementation was observed on zinc or copper absorption. No significant correlation was observed between plasma zinc and zinc absorption or between plasma copper and copper absorption. No significant correlation was observed between erythrocyte copper-zinc-dependent superoxide dismutase activity and copper absorption. CONCLUSIONS The study does not support the contention that iron supplements inhibit the absorption of zinc or copper in healthy breastfed infants at 6-9 mo of age. In addition, we did not find any age-related changes in zinc or copper absorption between 6 and 9 mo of age.