Adenylate kinase 9 is essential for sperm function and male fertility in mammals.

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 (AK9) 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.

An index framework founded on the future profit potential of female beef cattle to aid the identification of candidates for culling.

Meticulous culling decisions, coupled with careful breeding decisions, are fundamental to shifting a population distribution in the favorable direction and improving profit per cow. Nevertheless, there is a paucity of easy-to-use dynamic tools to aid in culling decisions in beef cattle. The motivation for the present study was to develop a monetary-based culling tool, here referred to as the Beef Female's Profit Potential (BFPP), to identify females for culling. The BFPP reflects the expected lifetime profitability of an individual female in a herd for the expected remainder of her lifetime; this profit included that of the beef female herself as well as her progeny. The BFPP index framework was composed of 4 subindexes reflecting the value of an animal: (1) as a nulliparae (this was voided if the cow had already calved), (2) for the remainder of her current parity, (3) summed across each of her expected remaining parities, and (4) when she is retained within the herd and not voluntarily culled. Each subindex was comprised of different components reflecting both genetic and non-genetic effects associated with each female. Transition matrices predicting the expected longevity of each female and their expected month of calving were also utilized in calculating the expected remaining lifetime profitability of each female. The BFPP index was validated on 21,102 beef cows as well as their harvested progeny from 875 herds by stratifying the cows, within herd, into 4 strata based on their BFPP. The mean of the within-herd correlation between the BFPP and the Irish national replacement (i.e., breeding) index was, on average, 0.45 indicating the shortcomings of the breeding index as a culling tool. Cows within the top BFPP stratum had a genetic expectation of accruing almost an additional €36 profit per calving, relative to cows within the worst stratum; when validated on the cow's own calving interval and survival performance as well as their progeny's carcass performance, the actual phenotypic value was estimated to be an additional €32 profit per calving. A proportion of this additional profit was due to the harvested progeny of the high BFPP cows having, on average, heavier, more conformed carcasses with less fat cover relative to their poor BFPP contemporaries. This BFPP framework is a useful and easy-to-use tool to aid in producer decision making on the choice of females to voluntarily cull but also on which replacement heifers to graduate into the mature herd.

Genetic parameters for variability in the birth of persistently infected cattle following likely in utero exposure to bovine viral diarrhea virus.

Genetic selection is an inexpensive and complementary strategy to traditional methods of improving animal health and welfare. Nonetheless, endeavors to incorporate animal health and welfare traits in international breeding programs have been hampered by the availability of informative phenotypes. The recent eradication program for bovine viral diarrhea (BVD) in the Republic of Ireland has provided an opportunity to quantify the potential benefits that genetic selection could offer BVD eradication programs elsewhere, as well as inform possible eradication programs for other diseases in the Republic of Ireland. Using a dataset of 188,085 Irish calves, the estimated direct and maternal heritability estimates for the birth of persistently infected calves following likely in utero exposure to BVD virus ranged from not different from zero (linear model) to 0.29 (SE = 0.075; threshold model) and from essentially zero (linear model) to 0.04 (SE = 0.033; threshold model), respectively. The corresponding genetic SD for the direct and maternal effect of the binary trait (0, 1) ranged from 0.005 (linear model) to 0.56 (threshold model) units and ranged from 0.00008 (linear model) to 0.20 (threshold model) units, respectively. The coefficient of direct genetic variation based on the linear model was 2.56% indicating considerable genetic variation could be exploited. Based on results from the linear model in the present study, there is the potential to reduce the incidence of persistent infection in cattle by on average 0.11 percentage units per year which is cumulative and permanent. Therefore, genetic selection can contribute to reducing the incidence of persistent infection in cattle. Moreover, where populations are free from persistent infection, inclusion of the estimated genetic merit for BVD in national breeding indexes could contribute to a preservation of a BVD-free status. Results from the present study can be used to inform breeding programs of the potential genetic gains achievable. Moreover, the approaches used in the present study can be applied to other diseases when data become available.