Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy ...bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (
) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.
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Heat stress in production agriculture can result in losses due to reduced growth or death. Currently, available climate models predict that duration and regional expansion of heat ...stress is likely to increase. The purpose of the present study was to determine the extent to which prenatal hyperthermia alters the response to subsequent heat stress. Pregnant sows were exposed to thermoneutral (TN; n = 9; stable 25°C) or heat stress (HS; n = 7; 24 hr cyclic 25–35°C) conditions for the duration of gestation. After weaning, resultant offspring were allowed to mature to three months before exposure to a constant temperature of 35°C for a period of 24‐hrs. Rectal temperatures (Tr) increased similarly between groups; however, skin temperature (Ts) was significantly higher following 16 and 20 hrs of heating in HS compared to TN and the cumulative effect of heating on Ts tended to be 1% higher in HS compared to TN (P = 0.06). The difference between Tr and Ts was 1.3°C and 2.2°C greater (P < 0.05) following 16 and 20 hrs of heating, respectively, and the cumulative difference was approximately 50% greater in HS compared to TN. These data indicate heat stress applied during prenatal development could modify fetal programming such that the response to heat stress encountered later in life is altered. Supported by USDA/NIFA.
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