Sire Conception Rate Research Articles

Genomic evaluation, breed identification, and discovery of a haplotype affecting fertility for Ayrshire dairy cattle

Genomic evaluations of dairy cattle in the United States have been available for Brown Swiss, Holsteins, and Jerseys since 2009. As of January 2013, 1,023 Ayrshires had genotypes in the North American database. Evaluation accuracy was assessed using genomic evaluations based on 646 bulls with 2008 traditional evaluations to predict daughter performance of up to 180 bulls in 2012. Mean gain in reliability over parent average for all traits was 8.2 percentage points. The highest gains were for protein yield (16.9 percentage points), milk yield (16.6 percentage points), and stature (16.2 percentage points). Twelve single nucleotide polymorphisms were useful for Ayrshire breed determination. Fewer breed-determining SNP were available for Ayrshires than for Holsteins, Jerseys, and Brown Swiss because of the similarity of Ayrshires and Holsteins. A haplotype that affects fertility was identified on chromosome 17 and traces back in the genotyped population to the bull Selwood Betty’s Commander (born in 1953). The haplotype carrier frequency for genotyped Ayrshires was 26.1%. Sire conception rate was decreased by 4.3±2.5 percentage points for carriers of the haplotype as determined by 618 matings of carrier sire by carrier maternal grandsire. Genomic evaluations for Ayrshires were officially implemented in the United States in April 2013.

Copy number variation of PRAMEY across breeds and its association with male fertility in Holstein sires

Multi-copy gene families are especially prevalent in the male-specific region (MSY) of the mammalian Y chromosome. Copy number variations (CNV) of these Y-linked gene families have been shown to affect human and animal fertility. The PRAMEY (Preferentially expressed antigen in melanoma, Y-linked) gene family is a newly identified, bovid-specific Y-linked gene family, which codes for a cancer/testis antigen that is expressed predominantly in testis and various tumors. The PRAMEY gene family is believed to play an important role in spermatogenesis and male fertility in cattle. The objective of this study was to investigate the CNV of PRAMEY within and across breeds and to determine whether CNV was associated with reproductive traits in Holstein bulls. A quantitative real-time PCR method was applied to measure the copy number of PRAMEY among 460 bulls using a Y-linked single copy gene, DDX3Y (DEAD box polypeptide 3, Y-linked), as a reference. The median copy number of PRAMEY was 13, ranging from 2 to 31. Significant variations in PRAMEY copy number were observed among 15 breeds investigated. Holstein bulls had the lowest median copy number (12), whereas Limousin bulls possessed the highest median copy number (26). Furthermore, bulls in the taurine lineage (13) had a significantly lower median copy number than those bulls in the indicine lineage (20). Association analysis revealed that PRAMEY copy number was correlated negatively with scrotal circumference (SC), relative scrotal circumference (RLSC), percentage of normal sperm (PNS), and nonreturn rate (NRR), but had no significant association with postthaw motility (PTM), incubated motility (IM), percentage of intact acrosome (PIA), sire conception rate (SCR), or relative breeding efficiency (RBE). The data from this study indicate that CNV of the PRAMEY gene family is associated with male reproductive traits and may serve as a valuable marker for sire fertility selection at an early age in cattle.

Associations of adiponectin and fertility estimates in Holstein bulls

Adiponectin is a pleiotropic regulator of numerous biological functions, including gonadal steroidogenesis and might play a role in sperm structures and functions. The objectives were to: (1) determine associations among serum concentrations of adiponectin, testosterone, and prolactin, and the sperm DNA fragmentation index; (2) associate sperm adiponectin mRNA abundance with estimates of fertility (sire conception rate); and (3) determine sperm protein expression of adiponectin and its receptor in pre- and postcapacitated sperm from Holstein bulls. In experiment 1, biweekly serum concentrations of adiponectin, prolactin, and testosterone were greater (P < 0.05) for high fertility bulls compared with average and low fertility bulls. Furthermore, sperm DNA fragmentation index was greater (P < 0.05) for low fertility compared with both average and high fertility bulls. In experiment 2, samples of sperm from a single collection from commercial Holstein bulls (N = 34) were used to evaluate relative sperm mRNA expression of adiponectin and its receptors, AdipoR1 and AdipoR2, and protein levels of adiponectin and its receptors, AdipoR1 and AdipoR2, in pre- and postcapacitation sperm. The mRNA abundance of adiponectin and its receptors, AdipoR1 and AdipoR2, were greater for high fertility bulls (>2 to ≤4 sire conception rate) compared with average (≥2 to ≤2) and low (>−2 to ≤−4) fertility bulls. Based on the sperm capacitation assay, average fertility bulls had a greater percentage of acrosome-reacted sperm at 5 hours than high and low fertility bulls, whereas high fertility bulls had a greater percentage of acrosome-reacted sperm than low fertility bulls. After capacitation, levels of adiponectin protein were lower in average fertility bulls, AdipoR1 was lower in all fertility groups, and AdipoR2 was lower in average and high fertility bulls. In conclusion, adiponectin and its receptors had vital roles in sperm structural and functional traits and consequently they were associated with fertility. In addition to its role in steroidogenesis and sperm capacitation, adiponectin might be involved in sperm-egg fusion and fertilization.

Inferring quantitative trait pathways associated with bull fertility from a genome-wide association study.

Whole-genome association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. As such, the objective of this study was to perform a pathway-based association analysis in Holstein dairy cattle in order to identify relevant pathways involved in bull fertility. The results of a single-marker association analysis, using 1,755 bulls with sire conception rate data and genotypes for 38,650 single nucleotide polymorphisms (SNPs), were used in this study. A total of 16,819 annotated genes, including 2,767 significantly associated with bull fertility, were used to interrogate a total of 662 Gene Ontology (GO) terms and 248 InterPro (IP) entries using a test of proportions based on the cumulative hypergeometric distribution. After multiple-testing correction, 20 GO categories and one IP entry showed significant overrepresentation of genes statistically associated with bull fertility. Several of these functional categories such as small GTPases mediated signal transduction, neurogenesis, calcium ion binding, and cytoskeleton are known to be involved in biological processes closely related to male fertility. These results could provide insight into the genetic architecture of this complex trait in dairy cattle. In addition, this study shows that quantitative trait pathways inferred from single-marker analyses could enhance our interpretations of the results of genome-wide association studies.

Short communication: A missense mutation in the PROP1 (prophet of Pit 1) gene affects male fertility and milk production traits in the US Holstein population

In previous studies, we reported significant associations of the POU1F1 pathway genes with reproduction and production traits in several dairy cattle populations. Polymorphisms in genes of this pathway were found to be associated with both female and male fertility traits in dairy cattle. The POU1F1 gene is a direct downstream target for the regulation of the prophet of Pit1 (PROP1) gene, also known as PROP paired-like homeobox 1. Interestingly, the position of PROP1 coincides with a quantitative trait locus affecting ovulation rate in cattle. Therefore, the objective of this study was to investigate whether PROP1 affects fertility and milk production traits in Holstein cattle. Using the DNA pooling sequencing approach, a missense single nucleotide polymorphism that replaces a histidine amino acid with an arginine was detected in exon 3 of PROP1. The arginine allele was found to be associated with a decrease in sire conception rate and an increase in productive life, protein yield, and net merit index in a population of 1,951 Holstein bulls. The transcription factors produced from the histidine and arginine isoforms are known to have different transcription, DNA binding, and regulation activities. As such, we propose that the association of the arginine isoform with decreased bull fertility is likely caused by reduced activity of this allele in male functions. The findings of this study suggest PROP1 polymorphisms as candidates in selection programs for fertility, health, and milk production traits in dairy cattle.

Comparative genomics between fly, mouse, and cattle identifies genes associated with sire conception rate

The decline in reproductive performance in cattle is of major concern to farmers and the dairy industry worldwide. Most fertility studies in cattle have focused on fertility of the cow, whereas the genetics of male fertility have not been thoroughly investigated. The present study hypothesizes that the high conservation of spermatogenesis genes from fly to human implies important roles of these genes in male fertility in cattle. To test this hypothesis, we performed an association analysis between highly conserved spermatogenesis genes and sire conception rate (SCR) in US Holsteins as a measure of bull fertility. Sequencing analysis revealed 24 single nucleotide polymorphisms (SNP) in 9 genes in the bull population using the pooled DNA sequencing approach. Five SNP previously identified in 5 genes from the POU1F1 pathway were also included in this study because they have shown significant associations with female and male fertility traits. Overall, 29 SNP located in 14 candidate genes were tested for association with sire conception rate in a population of 1,988 bulls. Three SNP located in MAP1B and 1 SNP in PPP1R11 showed significant associations with SCR. For the POU1F1 pathway, single gene analysis revealed significant associations of POU1F1 and STAT5A with SCR. Analysis of genotypic interactions between adjacent genes in the pathway revealed significant associations of STAT5A and UTMP genotypic combinations with SCR. The most significant spermatogenesis gene, MAP1B, was found to be associated with fertilization and blastocyst rates. Thus, the association of these genes with bull fertility testifies to the usefulness of the comparative genomics approach in selecting candidate male fertility genes.

Genome‐wide association study identifies candidate markers for bull fertility in Holstein dairy cattle

The decline in the reproductive efficiency of dairy cattle has become a challenging problem worldwide. Female fertility is now taken into account in breeding goals while generally less attention is given to male fertility. The objective of this study was to perform a genome-wide association study in Holstein bulls to identify genetic variants significantly related to sire conception rate (SCR), a new phenotypic evaluation of bull fertility. The analysis included 1755 sires with SCR data and 38,650 single nucleotide polymorphisms (SNPs) spanning the entire bovine genome. Associations between SNPs and SCR were analyzed using a mixed linear model that included a random polygenic effect and SNP genotype either as a linear covariate or as a categorical variable. A multiple testing correction approach was used to account for the correlation between SNPs because of linkage disequilibrium. After genome-wide correction, eight SNPs showed significant association with SCR. Some of these SNPs are located close to or in the middle of genes with functions related to male fertility, such as the sperm acrosome reaction, chromatin remodeling during the spermatogenesis, and the meiotic process during male germ cell maturation. Some SNPs showed marked dominance effects, which provide more evidence for the relevance of non-additive effects in traits closely related to fitness such as fertility. The results could contribute to the identification of genes and pathways associated with male fertility in dairy cattle.

Factors associated with frequency of abortions recorded through Dairy Herd Improvement test plans

Frequency of abortions recorded through Dairy Herd Improvement (DHI) testing was summarized for cows with lactations completed from 2001 through 2009. For 8.5million DHI lactations of cows that had recorded breeding dates and were >151d pregnant at lactation termination, the frequency of recorded abortions was 1.31%. Effects of year, herd-year, month, and pregnancy stage at lactation termination; parity; breed; milk yield; herd size; geographic region; and state within region associated with DHI-recorded abortion were examined. Abortions recorded through DHI (minimum gestation of 152d required) were more frequent during early gestation; least squares means (LSM) were 4.38, 3.27, 1.19, and 0.59% for 152 to 175, 176 to 200, 201 to 225, and 226 to 250d pregnant, respectively. Frequency of DHI-recorded abortions was 1.40% for parity 1 and 1.01% for parity ≥8. Abortion frequency was highest from May through August (1.42 to 1.53%) and lowest from October through February (1.09 to 1.21%). Frequency of DHI-recorded abortions was higher for Holsteins (1.32%) than for Jerseys (1.10%) and other breeds (1.27%). Little relationship was found between DHI-recorded abortions and herd size. Abortion frequencies for effects should be considered to be underestimated because many abortions, especially those caused by genetic recessives, go undetected. Therefore, various nonreturn rates (NRR; 60, 80, …, 200d) were calculated to document pregnancy loss confirmed by the absence of homozygotes in the population. Breeding records for April 2011 US Department of Agriculture sire conception rate evaluations were analyzed with the model used for official evaluations with the addition of an interaction between carrier status of the service sire (embryo's sire) and cow sire (embryo's maternal grandsire). Over 13million matings were examined using various NRR for Holstein lethal recessive traits (brachyspina and complex vertebral malformation) and undesirable recessive haplotypes (HH1, HH2, and HH3) as well as >61,000 matings for a Brown Swiss haplotype (BH1), and 670,000 matings for a Jersey haplotype (JH1). Over 80% of fertility loss occurred by 60d after breeding for BH1, HH3, and JH1, by 80d for HH2, by 100d for BY, and by 180d for HH1. For complex vertebral malformation, fertility loss increased from 40 to 74% across gestation. Association of undesirable recessives with DHI-recorded abortions ranged from 0.0% for Jerseys to 2.4% for Holsteins.

Association of CRISP2, CCT8, PEBP1 mRNA abundance in sperm and sire conception rate in Holstein bulls

The objective was to determine the association of mRNA expression of cystine rich secretary protein 2 (CRISP2), chaperonin containing T-complex protein 1, subunit 8 (CCT8), and phosphatidylethanolamine-binding protein 1 (PEBP1), in sperm of Holstein bulls with Sire Conception Rate (SCR) scores between −4 and +4. These proteins were involved in sperm capacitation and sperm-egg fusion. Samples of sperm obtained on a single day from Holstein bulls (N = 34) in a commercial AI centre were used to evaluate relative mRNA expression of CRISP2, CCT8, and PEBP1. The mRNA abundance of CRISP2 was positively correlated (r = 0.88; P < 0.002), CCT8 was negatively correlated (r = −0.87; P < 0.002), and PEBP1 was positively correlated (r = 0.83; P < 0.006) with SCR-scores. The means of CRISP2 mRNA abundance was greater among positive SCR-score bulls (2.5 to 8 fold), the means of CCT8 mRNA abundance was greater among the negative SCR-score bulls (9.5 to 3.5 fold), and the means of PEBP1 mRNA abundance was greater for the positive SCR-score bulls (5.4 to 7.7 fold). In multivariate regression models predicting SCR-scores, mRNA abundance of CCT8 was significantly associated with SCR-score in all models. In the presence of CRISP2 mRNA abundance in the model, the SCR score's predictability of PEBP1 was insignificant. However, in the absence of CRISP2 mRNA abundance in the model, the SCR-score's predictability of PEBP1 was significant. In multivariate regression models, CRISP2 and CCT8 mRNA expression in sperm accounted for 95% of the variance in Holstein bull's SCR-scores. In conclusion, Holstein bulls with greater CRISP2 and lower CCT8 mRNA expression in sperm had higher probabilities of siring calves.

Use of sexed semen and its effect on conception rate, calf sex, dystocia, and stillbirth of Holsteins in the United States

Use of sexed semen for artificial insemination of US Holstein heifers (1.3million breedings) and cows (10.8million breedings) in Dairy Herd Improvement herds was characterized by breeding year, parity, service number, region, herd size, and herd milk yield. Sexed semen was used for 1.4, 9.5, and 17.8% of all reported breedings for 2006, 2007, and 2008, respectively, for heifers, and for 0.1, 0.2, and 0.4%, respectively, for cows. For 2008 sexed semen breedings, 80.5 and 68.6% of use was for first services of heifers and cows, respectively. For cows, 63.1% of 2008 sexed semen use was for first parity. Mean sexed semen use within herd was the greatest for heifers in the Southwest (36.2%) and for cows in the Mideast (1.3%). Mean sexed semen use increased for heifers but changed little for cows as either herd size or herd mean milk yield increased. Availability of sexed semen was examined for Holstein bulls in active AI service; of 700 bulls born after 1993, 37% had sexed semen marketed by mid August 2009. Active AI bulls with marketed sexed semen were superior to average active AI bulls for evaluations of yield traits, productive life, somatic cell score, daughter pregnancy rate, service-sire calving ease, service-sire stillbirth, final score, sire conception rate, and lifetime net merit. The effect of sexed semen use on conception rate, calf sex, dystocia, and stillbirth also was examined for heifers and cows. Mean conception rate for heifers was 56% for conventional and 39% for sexed semen; corresponding conception rates for cows were 30 and 25%. For single births from sexed semen breedings, around 90% were female. Dystocia and stillbirth were more frequent for heifers (6.0 and 10.4%, respectively, for conventional semen; 4.3 and 11.3%, respectively, for sexed semen) than for cows (2.5 and 3.6%, respectively, for conventional semen; 0.9 and 2.7%, respectively, for sexed semen). Difficult births declined by 28% for heifers and 64% for cows with sexed semen use. Stillbirths were more prevalent for twin births except for sexed semen heifer breedings. Stillbirths of single male calves of heifers were more frequent for breedings with sexed semen (15.6%) than conventional semen (10.8%); a comparable difference was not observed for cows, for which stillbirth frequency of single male calves even decreased (2.6 vs. 3.6%). Overall stillbirth frequency was reduced by sexed semen use for cows but not for heifers.

Modeling Nuisance Variables for Prediction of Service Sire Fertility

The purpose of this research was to determine which (available) nuisance variables should be included in a model for phenotypic evaluation of US service sire conception rate (CR), based on field data. Alternative models were compared by splitting data into records for estimation and set-aside records, computing predictions using the estimation data, and then comparing predictions to bulls’ average CR in the set-aside data. Breedings for estimation were from January 1, 2003, to June 30, 2005, and set-aside records spanned July 1, 2005, to June 30, 2006. Only matings with known outcomes were included in either data set. Correlations and mean differences were the main statistics used to compare models. Nuisance variables considered were management groups based on herd-year-season-parity-registry (HYSPR) classes, year-state-month, cow age, DIM, and various combinations of lactation, service number, and milk yield. Preliminary analyses led to 1) selection of standardized lactational milk yield as the production variable for consideration and 2) modeling quantitative independent variables as categorical factors rather than linear and quadratic covariates. Two general strategies for management groups were tested, one where HYSPR groups were required to have an absolute specified minimum number of records and a second where groups were combined across registry, season, and parity subclasses until a minimum group size was achieved. Combining groups to a target size of 20 and including a herd-year into the evaluation provided it had a minimum of 10 breedings maximized correlation with future year CR and was chosen as the management grouping strategy for implementation. Combining groups implied that some groups had multiple seasons as well as parities, which was the reason for consideration of year-state-month and lactation as additional factors. The final nuisance variables selected for inclusion in the model for prediction of service sire CR were, in addition to HYSPR, year-state-month, lactation, service number, milk yield, cow age at breeding, an interval between breedings variable to account for lower CR following short estrus cycles, and the cow effect, partitioned as permanent environment and breeding value. This model maximized correlation with future year CR (55.14%), minimized mean square error (3.255), and had a mean difference of essentially 0.

Systematic Environmental, Direct, and Service Sire Effects on Conception Rate in Artificially Inseminated Holstein Cows

Result of insemination was verified for 329,314 artificial inseminations by 882 service sires to 97,245 Holstein cows in 1,075 herds between May 1970 and December 1983. Estimates of systematic environmental and genetic components of cow and service sire components of conception rate were obtained preliminary to development of a fertility monitoring system. Conception rate was 2.9% higher in stanchion than loose housed herds and 2.3% higher in grade than registered cows. Fall months were superior to winter months, the greatest difference being 6.1% between October and January. Conception rate increased with herd milk production, decreased with both increased cow age, and increased herd size in mature and old cows. Regions and inseminators within regions were highly variable. Conception may be influenced by semen price; however, week day of insemination and duration of semen storage had no effect. Conception rate decreased for semen by bulls 8 yr and older, was lowest for semen harvested in June, but no season of collection effect was detected. No genetic trends for cow and service sire conception rate were found; heritability and repeatability were .08 and .06, respectively. Genetic correlations between cow and service sire conception rate and these components with first lactation production and semen output measures were all near zero.Therefore, the relationship between sire fertility and daughter fertility is near zero.