One-Carbon Metabolism, Spermatogenesis, and Male Infertility

Abstract

Balanced diet is the natural source of micronutrients, such as folate and vitamins, vital for proper functioning of the body. One-carbon metabolic pathway along with folate and other vitamins plays an important role in DNA synthesis and in the establishment of epigenetic modifications like DNA/histone methylation. Spermatogenesis involves distinct cellular, genetic, and chromatin changes during the course of production of male gamete sperm. Folate and normal activity of 1-carbon metabolic pathway enzymes are central to nucleotide synthesis, methylation, and maintenance of genomic integrity as well as protection from DNA damage. As a result, polymorphisms in 1-carbon metabolic pathway genes affecting several physiological processes also have an impact on spermatogenesis and may affect directly or indirectly quality of sperm. Alterations in these processes may be a consequence of additive effect resulting from altered expression of 1-carbon metabolic pathway genes and/or inadequate folate/micronutrients supplementation. The present review provides an overview of different cellular and molecular events regulated by 1-carbon metabolic pathway enzymes and their impact on male reproductive health. It also summarizes the different studies where polymorphisms in the enzymes of 1-carbon metabolic pathway or folate deficiency are associated with male infertility and future prospects.

One‐carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats

“…Finally, we have previously shown in humans that varicocoele induces a state of DNA hypo-methylation that predisposes to DNA damage [12] and that is overcome by varicocoelectomy [13]. Singh et al [14] explain how the one-carbon cycle provides activated methyl groups necessary for the methylation of DNA and proteins, affecting both gene expression and protein function. Thus, the vitamin B complex provided with Condensyl is likely to be very relevant to the effects reported in the present study.…”

De Novo Assembly and Analysis of the Testes Transcriptome from the Menhaden, Bervoortia tyrannus

“…These activities lead to an increase in cellular uptake of amino acids, lipolysis, and blood sugar that promote the exponential growth of the testes. The sexual activation also requires the biosynthesis of purines and pyrimidines for DNA synthesis that is essential for the growth of the testes along with spermatogenesis [60]. Therefore, it is not surprising that the top Go Ontology assignments, functional characterizations, and metabolic analysis all share a similar trend of growth promotion within the testes.…”

Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

“…Even if supplement use is discontinued postconception, red cell folate levels can remain elevated for over 3 months (15), so folate pathway genotypes of the fetus (as well as the mother) could potentially interact with prepregnancy maternal folic acid supplementation. In addition, the genotype of the father may have subtle effects on sperm DNA quality (16) that are insufficient to cause infertility or obvious genetic abnormality, but may increase the likelihood of malignancy. Whether DNA damage in the sperm leads to disease outcome may depend in part on the health and DNA repair capacity of the oocyte (17,18).…”