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

Faruq, Abdullah Al; Widodo, Oky Setyo; Takagi, Mitsuhiro; Lestari, Tita Damayanti; Mursalim, Muhammad Fadhlullah; Laksono, Nanang Tedjo; Okawa, Hiroaki; Islam, Md Shafiqul; Maki, Shinichiro; Rakib, Tofazzal Md; Yabuki, Akira; Yamato, Osamu

doi:10.3390/ani15162407

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

by

Abdullah Al Faruq

^1,2

,

Oky Setyo Widodo

^3,4

,

Mitsuhiro Takagi

^3,4,

Tita Damayanti Lestari

⁴,

Muhammad Fadhlullah Mursalim

⁵

,

Nanang Tedjo Laksono

⁶,

Hiroaki Okawa

⁷,

Md Shafiqul Islam

^1,2

,

Shinichiro Maki

¹

,

Tofazzal Md Rakib

^1,2

,

Akira Yabuki

¹

and

Osamu Yamato

^1,4,*

¹

Laboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan

²

Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Khulshi, Chattogram 4225, Bangladesh

³

Laboratory of Theriogenology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan

⁴

Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60155, Indonesia

⁵

Study Program of Veterinary Medicine, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia

⁶

Prigen Conservation Breeding Ark-Taman Safari, Pasuruan 67157, Indonesia

⁷

Guardian Co., Ltd., Kagoshima 890-0033, Japan

^*

Author to whom correspondence should be addressed.

Animals 2025, 15(16), 2407; https://doi.org/10.3390/ani15162407 (registering DOI)

Submission received: 9 July 2025 / Revised: 13 August 2025 / Accepted: 14 August 2025 / Published: 16 August 2025

(This article belongs to the Special Issue Advances in Cattle Genetics and Breeding)

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Abstract

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 (FOXP3) 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 (p < 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 FOXP3 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.

Keywords: bovine FOXP3 gene; regulatory T (Treg) cell; Bali cattle; Jaliteng; water buffalo; Holstein Friesian cow; anti-Müllerian hormone; reproductive failure; infertility

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MDPI and ACS Style

Faruq, A.A.; Widodo, O.S.; Takagi, M.; Lestari, T.D.; Mursalim, M.F.; Laksono, N.T.; Okawa, H.; Islam, M.S.; Maki, S.; Rakib, T.M.; et al. The High Frequency of a G-Allele Variant of the FOXP3 Gene in Old Asian Cattle Breeds, Water Buffaloes, and Holstein Friesian Cows: A Potential Link to Infertility. Animals 2025, 15, 2407. https://doi.org/10.3390/ani15162407

AMA Style

Faruq AA, Widodo OS, Takagi M, Lestari TD, Mursalim MF, Laksono NT, Okawa H, Islam MS, Maki S, Rakib TM, et al. The High Frequency of a G-Allele Variant of the FOXP3 Gene in Old Asian Cattle Breeds, Water Buffaloes, and Holstein Friesian Cows: A Potential Link to Infertility. Animals. 2025; 15(16):2407. https://doi.org/10.3390/ani15162407

Chicago/Turabian Style

Faruq, Abdullah Al, Oky Setyo Widodo, Mitsuhiro Takagi, Tita Damayanti Lestari, Muhammad Fadhlullah Mursalim, Nanang Tedjo Laksono, Hiroaki Okawa, Md Shafiqul Islam, Shinichiro Maki, Tofazzal Md Rakib, and et al. 2025. "The High Frequency of a G-Allele Variant of the FOXP3 Gene in Old Asian Cattle Breeds, Water Buffaloes, and Holstein Friesian Cows: A Potential Link to Infertility" Animals 15, no. 16: 2407. https://doi.org/10.3390/ani15162407

APA Style

Faruq, A. A., Widodo, O. S., Takagi, M., Lestari, T. D., Mursalim, M. F., Laksono, N. T., Okawa, H., Islam, M. S., Maki, S., Rakib, T. M., Yabuki, A., & Yamato, O. (2025). The High Frequency of a G-Allele Variant of the FOXP3 Gene in Old Asian Cattle Breeds, Water Buffaloes, and Holstein Friesian Cows: A Potential Link to Infertility. Animals, 15(16), 2407. https://doi.org/10.3390/ani15162407

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

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