The aetiology of the decline in fertility in aged mares is multifactorial, with reduced oocyte quality being a major contributing factor. Nicotinamide adenine dinucleotide (NAD+) concentrations decline in all tissues with age including the follicular cells, which has been implicated as a cause of reduced oocyte quality in aged mammalian females. Nicotinic acid (NA) supplementation increases the concentration of NAD+ precursors in the follicular fluid of mares. Appropriate safe dose and treatment duration is unknown.
A nonrandomised crossover study design with a minimum 2 week washout period was employed utilising mares (n=13) between 15-22 years of age. Treatment was commenced from early oestrus with; 1) placebo, 2) 1.5g of NA, or 3) 3g of NA administered once daily. Following 4 days of treatment at the detection of a dominant follicle (>35mm), an ovulation induction agent was administered. Transvaginal aspiration (TVA) was performed 18-24 hours later to collect follicular fluid from the dominant follicle. Blood was collected prior to treatment and at aspiration. Serum and follicular fluid were analysed via mass spectrometry.
The concentrations of multiple key metabolites involved in the NAD+ biosynthesis and secretion in follicular fluid and serum were increased in both 3g/day and 1.5g/day NA supplementation groups. Supplementation with 3g/day NA had more profound effect. No metabolites concentration were reduced in follicular fluid or serum. Mild adverse effects were observed following administration of 3g/day NA.
Supplementary feeding with either 3g/day or 1.5g/day of NA for four days during oestrus increased the concentration of key NAD+ metabolites within follicular fluid and serum. Whilst the 3g/day dose resulted in more profoundly elevated metabolites, mild adverse effects were noted in the mares receiving this dose. Treatment with 1.5g/day may be a safer dose of NA in the mare to improve oocyte quality and therefore reproductive efficiency in this species.