Effect of folate deficiency on promoter methylation and gene expression of <i>Esr1, Cav1</i>, and <i>Elavl1</i>, and its influence on spermatogenesis

Yuan, Hongfang; Zhao, Kai; Zang, Yu; Liu, Chunyan; Hu, Zhiyong; Wei, Jiajing; Zhou, Ting; Liu, Ying; Zhang, Huiping

doi:10.18632/oncotarget.15731

Cited by 22 publications

(13 citation statements)

References 49 publications

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“…40 Our results are supported by a study in which supplementation of FA improved the increase in the sperm count to 74% in the men who took folic acid supplements. 41 In a randomized controlled trial performed by Landau et al 42 FA supplementation however did not improve overall semen quality. 42 Studies by Swayne et al 39 and Ebisch et al 43 parameters, chromatin damage or ESTR mutation frequency.…”

Section: Discussionmentioning

confidence: 92%

“…This can be explained by the fact that in the absence of sufficient folate levels, there is increased uracil deposition, causing breaks in the DNA structure and subsequent hypomethylation 39 . Moreover inadequate folate levels can lead to elevated homocysteine levels, which consequently inhibits enzymes involved during transcription and translation, thereby decreasing gene expression 40 . Our results are supported by a study in which supplementation of FA improved the increase in the sperm count to 74% in the men who took folic acid supplements 41 .…”

Section: Discussionmentioning

confidence: 99%

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Estimation of folic acid/micro nutrients levels; Does it reflect sperm parameters

et al. 2020

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Objective To study the impact of vitamin B12, folic acid (FA) and methylmalonic acid (MMA) on sperm parameters; count, motility and morphology leading to male fertility. Methods The cross‐sectional study comprised of one hundred and eighty‐six subjects with normal sperm parameters (fertile) and 88 subjects with abnormal sperm parameters labelled as “infertile” from a sample population of Karachi, Pakistan. Vitamin B12, FA and MMA levels in serum were analysed by enzyme linked immune sorbent assay. Unadjusted and adjusted prevalence ratio with their 95% CI were reported by using cox regression algorithm to assess the association of Vitamin B12, FA and MMA and other factors with male Infertility. Unadjusted and adjusted beta coefficients with 95% CI were reported by using linear regression analysis for assessing relationship of Vitamin B12, FA and MMA and other factors with semen parameters (count, motility and morphology); P value of <.05 was considered significant. Results It was declared that with every 1 unit increase in vitamin B12, FA and MMA the prevalence of infertility was decreased by 1%, 17% and 74%, respectively. Multivariate analysis revealed that vitamin B12, FA and MMA had a significant association with total sperm count, motility and morphology. The sperm parameters were also affected by increase in; LH, BMI and body fat %. There was a significant positive correlation of; LH with Vitamin B12 and FA (0.423 < 0.001, 0.338 < 0.001) and testosterone with vitamin B12 and FA (0.326 < 0.001, 0.291 < 0.001), respectively. Conclusion All the studied micronutrients; Vitamin B12, FA and MMA had a positive effect on sperm parameters; count, motility and morphology and the associated reproductive hormones which explains their role on reproductive functions required to acquire fertility.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Estimation of folic acid/micro nutrients levels; Does it reflect sperm parameters

et al. 2020

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“…; Yuan et al . ). Whilst not yet explored in Mtrr gt/gt mice, it is plausible that Mtrr gt/gt females might be more sensitive to the physiological effects of reduced oestrogen signalling resulting in ineffective haematopoiesis.…”

Section: Discussionmentioning

confidence: 97%

Abnormal folate metabolism causes age‐, sex‐ and parent‐of‐origin‐specific haematological defects in mice

Padmanabhan

Menelaou

Gao

et al. 2018

The Journal of Physiology

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Key points Folate (folic acid) deficiency and mutations in folate‐related genes in humans result in megaloblastic anaemia.Folate metabolism, which requires the enzyme methionine synthase reductase (MTRR), is necessary for DNA synthesis and the transmission of one‐carbon methyl groups for cellular methylation.In this study, we show that the hypomorphic Mtrrgt/gt mutation in mice results in late‐onset and sex‐specific blood defects, including macrocytic anaemia, extramedullary haematopoiesis and lymphopenia.Notably, when either parent carries an Mtrrgt allele, blood phenotypes result in their genetically wildtype adult daughters, the effects of which are parent specific.Our data establish a new model for studying the mechanism of folate metabolism in macrocytic anaemia aetiology and suggest that assessing parental folate status might be important when diagnosing adult patients with unexplained anaemia. AbstractThe importance of the vitamin folate (also known as folic acid) in erythrocyte formation, maturation and/or longevity is apparent since folate deficiency in humans causes megaloblastic anaemia. Megaloblastic anaemia is a type of macrocytic anaemia whereby erythrocytes are enlarged and fewer in number. Folate metabolism is required for thymidine synthesis and one‐carbon metabolism, though its specific role in erythropoiesis is not well understood. Methionine synthase reductase (MTRR) is a key enzyme necessary for the progression of folate metabolism since knocking down the Mtrr gene in mice results in hyperhomocysteinaemia and global DNA hypomethylation. We demonstrate here that abnormal folate metabolism in mice caused by Mtrrgt/gt homozygosity leads to haematopoietic phenotypes that are sex and age dependent. Specifically, Mtrrgt/gt female mice displayed macrocytic anaemia, which might be due to defective erythroid differentiation at the exclusion of haemolysis. This was associated with increased renal Epo mRNA expression, hypercellular bone marrow, and splenic extramedullary haematopoiesis. In contrast, the male response differed since Mtrrgt/gt male mice were not anaemic but did display erythrocytic macrocytosis and lymphopenia. Regardless of sex, these phenotypes were late onset. Remarkably, we also show that when either parent carries an Mtrrgt allele, a haematological defect results in their adult wildtype daughters. However, the specific phenotype was dependent upon the sex of the parent. For instance, wildtype daughters of Mtrr+/gt females displayed normocytic anaemia. In contrast, wildtype daughters of Mtrr+/gt males exhibited erythrocytic microcytosis not associated with anaemia. Therefore, abnormal folate metabolism affects adult haematopoiesis in an age‐, sex‐ and parent‐specific manner.

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“…More recently, there has been increasing focus on folate in relation to male fertility (36) . Marginal folate status has been associated both with erectile dysfunction (37,38) and with impaired fertility and spermatogenesis (36,39) .…”

Section: Discussionmentioning

confidence: 99%

Alcohol consumption among students and its relationship with nutritional intake: a cross-sectional study

Hillesund

Øverby

Valen

et al. 2020

Public Health Nutr.

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Objective: Excessive alcohol consumption during reproductive years may impact the integrity of developing eggs and sperm, potentially affecting the life-long health of future children. Inadequate diets could aggravate these preconception effects of alcohol. The aim of the present study was to assess the prevalence of excessive alcohol consumption and explore whether weekly alcohol intake is associated with energy and nutrient intake and adequacy of micronutrient intake among students. Design: Cross-sectional survey using a validated and reproducibility-tested food frequency questionnaire Setting: University of Agder, Norway, in 2018 Participants: 622 students (71% female) Results: More than 80% reported having consumed alcoholic beverages the past four weeks. One-third of men and 13% of women exceeded the upper recommended limit of 14 UK alcohol units per week. An inverse association between increasing alcohol intake and energy-adjusted micronutrient intake was evident for thiamine, phosphate, iron, zinc and selenium in men, and for vitamin A, β-carotene, vitamin E and C, thiamine, vitamin B6, folate, phosphorus, magnesium, potassium, iron, zinc and copper in women. A substantial proportion had vitamin D, folate, iron and iodine intakes below average requirement regardless of alcohol consumption level. The combination of prevalent alcohol use, decreasing micronutrient density of diet across alcohol consumption level, and a high probability of micronutrient inadequacy indicate reason for concern in a preconception public health perspective. Conclusions: Our findings call for investigations into young adults’ knowledge, reflections and beliefs regarding diet and alcohol use to understand how these behaviours could be improved ahead of parenthood.

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Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis

Cited by 22 publications

References 49 publications

Estimation of folic acid/micro nutrients levels; Does it reflect sperm parameters

Estimation of folic acid/micro nutrients levels; Does it reflect sperm parameters

Abnormal folate metabolism causes age‐, sex‐ and parent‐of‐origin‐specific haematological defects in mice

Alcohol consumption among students and its relationship with nutritional intake: a cross-sectional study

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