Sexual Dysfunction and Infertility in the Male Spina Bifida Patient

Nanfu Deng; Nannan Thirumavalavan; Jonathan A. Beilan; Alexander J. Tatem; Mark S. Hockenberry; Alexander W. Pastuszak; Larry I. Lipshultz


Transl Androl Urol. 2018;7(6):941-949. 

In This Article

The Genetics of Spina Bifida and Infertility

While certain genetic predispositions for spina bifida and genes causing infertility are known, genes associated with both spina bifida and male infertility have yet to be identified. Prior to the widespread use of prenatal folic acid, the incidence of neural tube defects among children born to men with spina bifida was 3.7%, significantly higher than the incidence in the general population.[16] In fact, the recurrence of neural tube defects in newborns increases from 1–5% if one parent or sibling has spina bifida to 15% if both parents have spina bifida.[36] Polymorphisms in homocysteine metabolism involving the enzyme methylenetetrahydrofolate reductase (MTHFR 677C→T) have been implicated in the heritability of neural tube defects and male infertility.[44,45] The reduced activity of MTHFR leads to low plasma folate, a vitamin essential to the development of fetal nervous system which controls sexual function, such as erection, ejaculation, testis development, and spermatogenesis, later in life.[18,20,45]

In mouse studies, knockouts in the apoB gene, a component of lipoprotein particles, have been implicated in both neural tube defects and male infertility.[46] In humans, significant differences in the genotype distributions of apoB signal peptide polymorphism were seen in men with oligoasthenoteratozoospermia and fertile men.[47] Other candidate genes implicated in male infertility also affect lipid metabolism, such as apoE receptor-2 gene (apoER2), acid sphingomyelinase gene (ASM), and ATP-binding cassette transporter 1 gene (ABCA1).[48–50] Despite the many candidate genes that have been linked to either infertility or spina bifida, none have been definitively found to cause spina bifida and its associated testis failure. Perhaps the least studied aspect of infertility in spina bifida men, the genetic basis of this association represents a significant direction for future research and an exciting avenue for future treatment of infertility among this unique patient population.