In collaboration with the laboratory of Dr. Brenda Eskenazi at the School of Public Health, University of California at Berkeley, we have been investigating the effects of age on semen quality. Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. We recruited 97 non-smoking men (aged 22-80 years) without known fertility problems. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: - 0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. We also determined whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) was associated with semen quality. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and progressive motility (P=0.09); between vitamin E intake and progressive motility (P=0.04) and TPMS (P=0.05); and between beta-carotene intake and sperm concentration (P=0.06) and progressive motility (P=0.06). Folate and zinc intake were not associated with improved semen quality.

In collaboration with Norman Arnheim at the Molecular and Computational Biology Program, University of Southern California, Los Angeles, CA and Ethylin Wang Jabs at the Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, Department of Pediatrics, The Johns Hopkins University, Baltimore, we investigated whether mutations for achondroplasia and Apert Syndrome (AS) were significantly increased in sperm of older men. The incidences of both these diseases in children increase exponentially with paternal age. PCR-based assays were used to measure the mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia and FGFR2 gene that causes AS. The results showed the frequencies of mutations for these genes were increased in sperm of older men. However, the magnitude of the increase in mutation frequency with age was insufficient to explain why older fathers have a greater chance of having a child with these conditions. Additional studies are in progress to determine, whether the frequencies of chromosomal abnormalities are elevated as function of age.