The Role Age Plays In Male Fertility

                                We all know fertility decreases with age for women. But what about increasing age and male fertility? Believe it or not, age plays a larger role than you would expect in male fertility. There are many factors contributing to the decline of fertility in men as they age. It's not as simple as producing more sperm. In fact, overproduction and higher sperm concentrations DO NOT increase male fertility (8).

How Age Changes The Male Reproductive System

The Testes and Sperm Production

As a male ages, the testes produce sperm with less sperm motility; meaning they swim slower. The older a man becomes the less chance sperm has at reaching the female's egg, and the longer it will take for the woman to fall pregnant. The decline of sperm motility is a gradual and constant process in a man's life after he turns about 20 years old (7). A decrease in sperm motility also slows the development of sperm. The sperm needs to travel from the testes to the ejaculatory duct through a tube called the epididymis. In the epididymis, the sperm matures and acquires more motility (swim speed). With increasing age, the maturation process of sperm within the epididymis slows (4). This creates fundamental changes in a sperm's motility, reducing the speed at which sperm fully mature. These changes reduce sperm motility, making sperm less likely to reach maturity by the time they have a chance to fertilize a female's egg — greatly reducing the chance of conception.

Decline Of Male Fertility And The Prostate Gland

The testes are not the only male reproductive organ that reduces a man's fertility with age. The prostate gland also plays a role male fertility. The prostate gland is the second largest contributor in the production of seminal fluid/semen. As a man ages, the prostates ability to produce adequate levels of seminal fluid decreases — lowering his fertility. The prostate undergoes changes with age that lower its production of an important protein called fertilization-promoting peptide (FPP). FPP allows sperm to be more biologically active and more likely to fertilize the egg. Lower levels of FPP are known to cause a decrease in overall male fertility (6). The older a man becomes, the smooth muscle surrounding the prostate gland weakens — leading to less fluid released by the prostate during ejaculation. Less water and proteins, such as FPP, released by the prostates results in a major decrease in male fertility 12).

Genetic Quality of Sperm and Miscarriages     

In an aging male, the decline of the testes, epididymis and the prostate gland, create a triple crown of fertility reduction. But the effects of age on male fertility does not end there. The genetic quality of a man's sperm declines with age. Miscarriage becomes more likely as the genetic quality of sperm decreases.The older a man becomes, the more likely there are to be chromosomal defects found within his sperm (11). Chromosomal defects in sperm can lead to incomplete fetal development and miscarriage.    

Sperm Mutations Lead to Diseases

In general, single point genetic mutations increase in sperm with male age. Some diseases are brought on by single point mutations such as Achondroplasia (most common cause of dwarfism) and Apert Syndrome (causes deformities in the hands, feet, face, and skull). However, the genetic mutations that cause Achondroplasia and Apert syndrome do increase with age, the frequency of these autosomal diseases increases more than expected (13). This is due to increases in sperm with these genetic mutations being selected for by the male for fertilization, over sperm without these genetic mutations (3). The cause of the male selecting sperm with these specific genetic defects for reproduction is unknown, but likely due to the mutations giving sperm reproductive advantage over other sperm.   

Paternal Age and Mental Health

Paternal Age And Schizophrenia

The older a man is when he fathers a child, the more risk the child has during their life to develop schizophrenia (1). Schizophrenia is a complex mental health disorder that is not fully understood by science. There are a large range of genetic mutations, environmental triggers and life history events that contribute to the development of schizophrenia. Increased paternal age increases the likelihood of schizophrenia, regardless of a positive family history of schizophrenia. Male age increases the amount of de novo mutations (mutations that are present in the sperm but not the father), which is thought to be the connection between schizophrenia in the offspring of fathers of older ages (9,10). Due to its complex nature, many genes contribute to the development schizophrenia over a lifetime. The more mutations found in sperm, the more likely genes playing a role in the development of schizophrenia will be affected.

Preeclampsia And Neural Development  

Paternal age also increases the likelihood of schizophrenia due to the association of paternal age to pre-eclampsia (5).  Preeclampsia poses a lot of stress on the nervous system of a growing fetus. This stress alters gene expression and developing neural connections during development, creating a favorable environment for schizophrenia to develop.

Advanced Paternal Age And Autism Spectrum Disorder (ASD)

With increasing paternal age, the risk of the child developing autism spectrum disorders (ASD) increases (2). ASD is a broad term used to describe a spectrum of neurological disorders such as:

• Autism
• Asperger syndrome
• Childhood disintegrative disorder
• Pervasive developmental disorder

People with ASD experience trouble socializing, connecting/communicating with other people, and tendencies to engage in repetitive behaviors that reduce a person's ability to function in society.  

Take Aways

Age and fertility go hand in hand — for both men and women.You may not have thought about the decline of male fertility with age before reading this article, or you may have had a general idea that fertility decreases with age in women and men. Below is a quick summary of the main points surrounding male age and fertility:

• More sperm does not equal more fertility
• Sperm develop/mature slower in older men
• The ability of sperm to swim declines with age
• More chromosomal defects are found in the sperm of older men
• Sperm mutation rate increases with age
• Prostate contributes fewer fluids to semen with older age
• With age, the prostate produces less fertilization-promoting peptide (FPP)
• The older a man is, the less likely his sperm will fertilize a female egg
• Miscarriages are more likely with increased paternal age
• There is an increased risk of preeclampsia during a pregnancy with an older man
• Schizophrenia is more frequent in the offspring of older men
• Higher rates of achondroplasia in children with older fathers
• Higher rates of Apert’s syndrome in children with older fathers
• Increased risk of developing autosomal diseases in the offspring of older fathers
• Older paternal ages increase risk of autism spectrum disorders (ASD)

Although there are significant decreases in male fertility, usually becoming noticeable after the age of 30, female age is the largest contributing factor affecting fertility. You can mitigate the effects of age and fertility through diet and lifestyle changes that are going to be specific to you. Do you have an MTHFR mutation? Are you smoking? Are you exercising? Do you have low or high homocysteine levels? What supplements will help increase my fertility? These are all simple questions to ask yourself and are great places to start if you are having fertility issues!

References

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2. Durkin, M. S., Maenner, M. J., Newschaffer, C. J., Lee, L. C., Cunniff, C. M., Daniels, J. L., ... & Schieve, L. A. (2009). Advanced Parental Age and the Risk of Autism Spectrum Disorder. Obstetrical & Gynecological Survey, 64(4), 223-225.
3. Goriely, A., McVean, G. A., Röjmyr, M., Ingemarsson, B., & Wilkie, A. O. (2003). Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science, 301(5633), 643-646.
4. Hamilton, D., & Naftolin, F. (Eds.). (1981). Basic reproductive medicine. MIT Press.
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7. Kidd, S. A., Eskenazi, B., & Wyrobek, A. J. (2001). Effects of male age on semen quality and fertility: a review of the literature. Fertility and sterility, 75(2), 237-248.
8. Kühnert, B., & Nieschlag, E. (2004). Reproductive functions of the ageing male. Human reproduction update, 10(4), 327-339.
9. Malaspina, D., Corcoran, C., Fahim, C., Berman, A., Harkavy‐Friedman, J., Yale, S., ... & Gorman, J. (2002). Paternal age and sporadic schizophrenia: evidence for de novo mutations. American Journal of Medical Genetics Part A, 114(3), 299-303.
10. Malaspina, D., Harlap, S., Fennig, S., Heiman, D., Nahon, D., Feldman, D., & Susser, E. S. (2001). Advancing paternal age and the risk of schizophrenia. Archives of general psychiatry, 58(4), 361-367.
11. Risch, N., Reich, E. W., Wishnick, M. M., & McCarthy, J. G. (1987). Spontaneous mutation and  parental age in humans. American journal of human genetics, 41(2), 218.
12. Schneider, E. L. (1978). The aging reproductive system. Raven Press.
13. Tiemann-Boege, I., Navidi, W., Grewal, R., Cohn, D., Eskenazi, B., Wyrobek, A. J., & Arnheim, N. (2002). The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proceedings of the National Academy of Sciences, 99(23), 14952-14957.