Can Nicotinamide Adenine Dinucleotide (NAD⁺) and Sirtuins Be Harnessed to Improve Mare Fertility?

Years of sire and dam selection based on their pedigree and athletic performance has resulted in a reduction in the reproductive capability of horses. Mare age is considered a major barrier to equine reproduction largely due to an increase in the age at which mares are typically bred following the end of their racing career. Nicotinamide adenine dinucleotide (NAD⁺) and its involvement in the activation of Sirtuins in fertility are an emerging field of study, with the role of NAD⁺ in oocyte maturation and embryo development becoming increasingly apparent. While assisted reproductive technologies in equine breeding programs are in their infancy compared to other livestock species such as cattle, there is much more to be learnt, from oocyte maturation to early embryo development and beyond in the mare, which are difficult to study given the complexities associated with mare fertility research. This review examines what is already known about the role of NAD⁺ and Sirtuins in fertility and discusses how NAD⁺-elevating agents may be used to activate Sirtuin proteins to improve equine breeding and embryo production programs both in vivo and in vitro.