Infertility (ABHD16B-related)

Gene: ABHD16B

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ABHD16B gene: c.652C>T, p.(Glu218 STOP), exon1, Chr.13.

Medical system: Reproductive

Breed: Holstein

Age of onset of symptoms: At sexual maturity.

Infertility can be caused by multiple factors including environmental, infectious and/or genetic.  A German Holstien bull (Tarentino) with normal sperm morphology, motility and concentration was judged completely infertile after 412 unsuccessful inseminations.  A molecular analysis showed that the bull had a homozygous mutation in the ABHD16B, and further that both of its parents were carriers for the same mutation. The ABHD16B gene is found in vertebrates that reproduce via internal fertilisation; it codes for an enzyme involved in lipid biosynthesis found in Leydig and epididymal cells of the testes.  Although this enzyme is not expressed in spermatozoa it is believed to be important for the maturation of the plasma membrane of spermatozoa and for proper sperm capacitation.  In a survey of 34 bulls that were close relatives of Tarentino, a carrier frequency of 53% was observed, with a possible correlation to sub-fertility.  In a larger survey of 2052 animals, a carrier frequency of 0.97% was recorded, while in a further survey of 222,645 animals a carrier frequency of 0.36% was observed. It is felt that a mutation with a negative effect on fertility could only exist at very low frequencies within a large population but may still be the cause of unexplained infertility.

Note that mutations in additional genes are reported to cause infertility in cattle:

TMEM95 gene, OMIA link [1902-9913]

ARMC3 gene, OMIA link [1334-9913]

References:

OMIA link: [2561-9913]

Shan S, Xu F, Hirschfeld M, et al. (2022) α/β-Hydrolase D16B Truncation Results in Premature Sperm Capacitation in Cattle. Int J Mol Sci 23:7777. [35887122]

Shan S, Xu F, Bleyer M, et al. (2020) Association of α/β-Hydrolase D16B with Bovine Conception Rate and Sperm Plasma Membrane Lipid Composition. Int J Mol Sci 21:627. [pm/31963602]

With contributions by: Sarah-Isa Gagné and Catherine Prévost, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).