The High Frequency of a G-Allele Variant of the <i>FOXP3</i> Gene in Old Asian Cattle Breeds, Water Buffaloes, and Holstein Friesian Cows: A Potential Link to Infertility

Reproductive failure in cattle production is a global concern and is influenced by various factors, including genetic alterations. This study explored the relationship between an X-linked single-nucleotide variant (NC_037357.1: g.87298881A>G, rs135720414) in the upstream of the bovine forkhead box P3 (<i>FOXP3</i>) gene and infertility. To this end, we examined the genotypes of the variant in old Asian cattle breeds, including 48 Bali and 5 Jaliteng cattle, and 20 water buffaloes, which have recently shown subclinical signs of infertility and repeated breeding problems among populations in Indonesia. We also examined the genotypes in 69 parous and 39 non-parous Holstein Friesian (HF) cows and investigated the relationship between the genotypes and serum concentration of anti-Müllerian hormone (AMH). The G allele frequency was markedly high in Bali (0.944) and Jaliteng cattle (0.714), and water buffaloes (1), suggesting that the G allele may be originally a wild-type variant in old Asian cattle and buffaloes. In HF cows, the G allele frequency was moderately high, and the AMH concentration was significantly lower (<i>p</i> < 0.05) in parous cows carrying the G allele (A/G and G/G genotypes) than in parous cows with the A/A genotype. In contrast, there were no significant differences in AMH concentrations among the three genotypes of non-parous HF cows. This suggests that both G allele and aging are associated with infertility in HF cows. In conclusion, the G allele of the <i>FOXP3</i> gene variant may potentially be associated with infertility in different bovine breeds and species. Therefore, special attention should be paid to this variant, and infertility in bovine herds may be improved by selection and/or introduction of the A allele.