TY - JOUR

T1 - Maternal intake of folate and folic acid during pregnancy and markers of male fecundity

T2 - A population-based cohort study

AU - Gaml-Sørensen, Anne

AU - Brix, Nis

AU - Høyer, Birgit Bjerre

AU - Tøttenborg, Sandra Søgaard

AU - Hougaard, Karin Sørig

AU - Bonde, Jens Peter Ellekilde

AU - Clemmensen, Pernille Jul

AU - Ernst, Andreas

AU - Arendt, Linn Håkonsen

AU - Olsen, Sjurdur Frodi

AU - Granström, Charlotta

AU - Henriksen, Tine Brink

AU - Toft, Gunnar

AU - Ramlau-Hansen, Cecilia Høst

N1 - © 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.

PY - 2023

Y1 - 2023

N2 - BACKGROUND: Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of the developing reproductive organs.OBJECTIVES: To examine the association between maternal intake of folate from diet and folic acid from supplements during pregnancy and markers of fecundity in young men.MATERIALS AND METHODS: We conducted a follow-up study using a Danish mother-son cohort of 787 young men born 1998-2000. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analyzed according to total folate calculated as dietary folate equivalents from diet and supplements in midpregnancy, using multivariable negative binomial regression models. Total folate was analyzed in quintiles, continuous per standard deviation decrease (SD: 318 μg/day) and as restricted cubic splines.RESULTS: Low maternal intake of total folate was associated with lower total sperm count (-5% (95% confidence intervals [CI]: -11%; 2%)), a lower proportion of non-progressive and immotile spermatozoa (-5% [95% CI: -8%; -3%]), and lower testes volume (-4% [95% CI: -6%; -2%]) per SD decrease in total folate intake. Spline plots supported these findings.DISCUSSION: The finding of a lower proportion of non-progressive and immotile spermatozoa, and hence a higher proportion of motile spermatozoa, in men of mothers with a lower intake of total folate in midpregnancy was surprising and may be a chance finding.CONCLUSION: Lower maternal intake of total folate in midpregnancy was associated with lower sperm count and lower testes volume, however, also with a lower proportion of non-progressive and immotile spermatozoa in adult men. Whether this actually affects the ability to obtain a pregnancy warrants further investigation.

AB - BACKGROUND: Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of the developing reproductive organs.OBJECTIVES: To examine the association between maternal intake of folate from diet and folic acid from supplements during pregnancy and markers of fecundity in young men.MATERIALS AND METHODS: We conducted a follow-up study using a Danish mother-son cohort of 787 young men born 1998-2000. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analyzed according to total folate calculated as dietary folate equivalents from diet and supplements in midpregnancy, using multivariable negative binomial regression models. Total folate was analyzed in quintiles, continuous per standard deviation decrease (SD: 318 μg/day) and as restricted cubic splines.RESULTS: Low maternal intake of total folate was associated with lower total sperm count (-5% (95% confidence intervals [CI]: -11%; 2%)), a lower proportion of non-progressive and immotile spermatozoa (-5% [95% CI: -8%; -3%]), and lower testes volume (-4% [95% CI: -6%; -2%]) per SD decrease in total folate intake. Spline plots supported these findings.DISCUSSION: The finding of a lower proportion of non-progressive and immotile spermatozoa, and hence a higher proportion of motile spermatozoa, in men of mothers with a lower intake of total folate in midpregnancy was surprising and may be a chance finding.CONCLUSION: Lower maternal intake of total folate in midpregnancy was associated with lower sperm count and lower testes volume, however, also with a lower proportion of non-progressive and immotile spermatozoa in adult men. Whether this actually affects the ability to obtain a pregnancy warrants further investigation.

U2 - 10.1111/andr.13364

DO - 10.1111/andr.13364

M3 - Journal article

C2 - 36524586

VL - 11

SP - 537

EP - 550

JO - Journal of Andrology

JF - Journal of Andrology

SN - 2047-2919

IS - 3

ER -