Date of Award:

8-2024

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

Ralph Meyer

Committee

Ralph Meyer

Committee

Mirella Meyer-Ficca

Committee

Jeffrey Mason

Abstract

In both humans and mice Nicotinamide Adenine Dinucleotide (NAD) levels and sperm DNA integrity both decline with age. However, whether these two processes are linked or independent of each other remains to be determined. Discovering if these two events are linked is critical as couples increasing delay childbearing into their 30s and 40s. Increased age of fathers increases the risk of adverse health effects upon offspring and pregnancy. Known adverse health consequences upon pregnancies and offspring, including decreased rates of natural pregnancy, decreased rates of assisted reproductive techniques, increased pregnancy loss, and increased rates of diseases in offspring such as skeletal dysplasia, apert syndrome, achondroplasia, autism and schizophrenia. NAD itself is required for DNA repair and energy metabolism that are essential for maintaining a stable internal environment in humans and mice. To study declining sperm DNA integrity and declining NAD levels a mouse model was utilized that decoupled age from declining NAD levels as young adult mice were made to have low NAD levels. NAD levels were measured in the mice in blood and tissue along with sperm DNA damage. The sperm DNA damage of the mice with low NAD levels was compared to sperm DNA integrity of old mice and young adult control mice with normal NAD levels. By decoupling aging from low levels of NAD the comparison to the controls and old mice allowed for similarity or differences of these two groups identity if low levels of NAD contribute to declining sperm DNA integrity. The relationship between age, NAD levels and sperm DNA integrity was further elucidated with a small human study of healthy individuals in which sperm parameters, sperm DNA integrity and blood NAD levels were quantified.

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