Folate and human reproduction

Folates belong to the vitamin B group and are involved in a large number of biochemical processes, particularly in the metabolism of homocysteine. Dietary or genetically determined folate deficiency leads to mild hyperhomocysteinemia, which has been associated with various pathologies. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation. Whereas the involvement of folate metabolism and homocysteine in ageing-related diseases, in several developmental abnormalities and in pregnancy complications has given rise to a large amount of scientific work, the role of these biochemical factors in the earlier stages of mammalian reproduction and the possible preventive effects of folate supplementation on fertility have, until recently, been much less investigated. In the present article, the possible roles of folates and homocysteine in male and female subfertility and related diseases are systematically reviewed, with regard to the epidemiological, pathological, pharmacological and experimental data of the literature from the last 25 years.

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Impact of folate and homocysteine metabolism on human reproductive health

https://air.unimi.it/bitstream/2434/169018/2/YCLNU1789.pdf

Micronutrients in pregnancy: Current knowledge and unresolved questions

Maternal homocysteine and small-for-gestational-age offspring: systematic review and meta-analysis

Intrauterine and early neonatal life is a period of physiological plasticity, during which environmental influences may produce long-term effects. Both undernutrition and overnutrition during this period have been shown to change disease risk in adulthood. These effects are influenced by the type, timing and duration of inappropriate nutrition and by the previous nutritional environment and may not be reflected in changes in body size. An understanding of the interaction between nutrient imbalance and alteration of gene expression is likely to be the key to optimising future health outcomes.

Nutritional programming of adult disease.

OBJECTIVE: To assess associations between vitamin-dependent homocysteine me ta bolism and vascular-related pregnancy complications by considering interval bet ween delivery and postpartam investigation and maternal age. METHODS: Casecontro l study performed at the University Medical Center Nijmegen in the Netherlands. Patients had experienced pregnancy-induced hypertension (n = 37), preeclampsia (n = 144), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 104), recurrent early pregnancy loss (n = 544), abruptio placentae (n = 135), intrauterine growth restriction (n = 144), or intrauterine fetal death (n = 104) . Controls comprised 176 women with uncomplicated obstetric histories. Oral meth ionine loading tests and fasting vitamin profiles were performed more than 6 wee ks after delivery. Odds ratios and 95%confidence intervals were calculated afte r logistic regression analysis. RESULTS: Hyperhomocysteinemia was associated wit h an approximately 2-fold to 3-fold increased risk for pregnancy-induced hype rtension, abruptio placentae, and intrauterine growth restriction. Cobalamin def iciency was associated with HELLP syndrome, abruptio placentae, intrauterine gro wth restriction, and intrauterine fetal death. Pyridoxal 5phosphate deficiency i ncreased the risk for pregnancy-induced hypertension 4-fold. These association s lost their significance after adjustment for time interval and maternal age. H igh red cell folate was associated with a decreased risk for abruptio placentae and intrauterine growth restriction. An increased creatinine concentration was a ssociated with pregnancy-induced hypertension, preeclampsia, HELLP syndrome, an d abruptio placentae. CONCLUSION: Hyperhomocysteinemia and vitamin deficiencies are largely determined by the interval between delivery and postpartum investiga tion and by maternal age. Time interval and maternal age should be considered in the risk estimation for vascular-related pregnancy complications.

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Hyperhomocysteinemia, pregnancy complications, and the timing of investigation