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The objective of the current study was to examine phenotypic fertility performance and survival, and to gain insight into underlying factors that may contribute to greater fertility performance in 2 divergent genetic groups (GG) of Holstein-Friesian, selected using the Irish Economic Breeding Index (EBI). The GG were evaluated across 3 spring calving pasture-based feeding treatments (FT) over 4 yr. The 2 divergent GG were (1) high EBI; representative of the top 5% nationally (elite), and (2) EBI representative of the national average (NA). In each year, 90 elite and 45 NA cows were randomly allocated to 1 of 3 FT: control, lower grass allowance, and high concentrate. No interaction between GG and FT was observed for any of the measures of fertility investigated. The elite cows achieved significantly greater pregnancy rate to first service (+14.9 percentage points), and significantly greater pregnancy rates after 21, 42, and 84 d of breeding (+17.3, +15.2, and +9.6 percentage points, respectively) compared with NA. The number of services per cow was fewer for elite (1.57) compared with NA (1.80). The interval from mating start date to pregnancy was significantly shorter for elite cows compared with NA. The elite cows maintained greater mean body condition score than NA throughout the study (2.91 vs. 2.72), and had greater body condition score at calving, artificial insemination, and drying off compared with NA. The elite cows had greater mean circulating concentrations of insulin-like growth factor-1 compared with NA. No significant effect was observed of GG on commencement of luteal activity, or progesterone profile variables. Greater survival to the start of fifth lactation was observed for elite cows. The elite cows were 43% less likely to be culled than NA by the beginning of the fifth lactation. The results highlight the success of the Economic Breeding Index to deliver reproductive performance and longevity consistent with industry targets across a range of seasonal pasture-based FT. The results also clearly demonstrate the potential of appropriate genetic selection to reverse negative fertility trends incurred during previous decades of selection for milk production alone., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

The objective of this study was to evaluate the associations between corpus luteum (CL) status, uterine health, body condition score (BCS), metabolic status, and parity at wk 3 and 7 postpartum in seasonal-calving, pasture-based, lactating dairy cows. The associations between those phenotypes and individual genetic traits were also evaluated. First- and second-parity spring-calving lactating dairy cows (n = 2,600) from 35 dairy farms in Ireland were enrolled. Farms were visited every 2 weeks; cows that were at wk 3 (range 14 to 27 DIM) and wk 7 (range 42 to 55 DIM) postpartum were examined. Body condition score was measured using a scale of 1 to 5 with 0.25 increments. Transrectal ultrasound examination was performed at wk 3 and 7 postpartum to determine presence or absence of CL and ultrasound reproductive tract score. Blood samples were collected at each visit and the concentrations of glucose, β-hydroxybutyrate (BHB), and fatty acids (FA) were analyzed by using enzymatic colorimetry. Cows were grouped into 3 BCS categories [low (≤2.5), target (≥2.75 and ≤3.25), and high (≥3.5)]; 2 CL status categories: (present or absent); 2 uterine health status (UHS) categories (normal and abnormal); and 3 metabolic status categories [good (high glucose, low fatty acids and BHB), poor (low glucose, high fatty acids and BHB), and moderate (all other combinations)]. Fisher's exact test was used to test associations between variables and was supplemented by logistic regression. We found associations between UHS (wk 3 and 7), BCS (wk 3 and 7), parity (wk 3 and 7) metabolic status (wk 3), and predicted transmitting ability for calving interval (PTA for CIV; wk 3) and CL status. Cows that had abnormal UHS, low BCS, primiparity, and poor metabolic status, and were in the quartile with the greatest PTA for CIV were less likely to have had CL present at wk 3 and 7 postpartum. We also found associations between CL status (wk 3 and 7), BCS (wk 3 and 7), parity (wk 3 and 7), and PTA for CIV (wk 3) and UHS. Cows that did not have a CL present had low BCS, primiparity, and that were in the quartile with greatest PTA for CIV, had a greater risk of abnormal UHS at wk 3 and 7 postpartum. We observed strong associations between CL status, UHS, BCS, metabolic status, parity, and individual genetic traits at wk 3 and 7 postpartum in seasonal-calving, pasture-based lactating dairy cows. Achieving target BCS and good metabolic status, and selecting cows based on PTA for CIV, are all expected to increase the likelihood of hastening the resumption of estrous cyclicity and enhancing uterine health during the postpartum period., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to (1) characterize the distribution and variability of plasma anti-Müllerian hormone (AMH) concentration; (2) evaluate factors associated with phenotypic variation in plasma AMH; (3) examine the associations between categories of plasma AMH and reproductive outcomes [pregnancy to first artificial insemination (P/AI), and pregnancy rates within 21, 42, and 84 d after the mating start date (MSD)]; (4) estimate pedigree and genomic heritability for plasma AMH; and (5) identify and validate SNP associated with phenotypic variation in plasma AMH. Plasma AMH concentration (pg/mL) was determined from a blood sample collected (mean ± standard deviation) 10 ± 2 d after first insemination at detected estrus (IDE) in 2,628 first- and second-parity Irish dairy cows. Overall, plasma AMH had a positively skewed distribution with mean (± standard deviation), median, minimum, and maximum concentrations of 326 ± 231, 268, 15, and 2,863 pg/mL, respectively. Plasma AMH was greatest for Jersey, followed by Holstein × Jersey, Holstein × Norwegian Red, and Holstein cows (410, 332, 284, and 257 pg/mL, respectively). Second-parity cows had greater plasma AMH than first-parity cows (333 vs. 301 pg/mL, respectively). Samples collected at 7 and 8 d after first IDE had lesser plasma AMH than those collected on d 9, 10, 11, 12, and 13 after first IDE (291 and 297 vs. 317, 319, 331, 337, and 320 pg/mL). Plasma AMH was not associated with either body condition score at first IDE or the interval from calving to MSD. Cows were categorized into low (≤150 pg/mL; n = 526; lowest 20%), intermediate (>150 to ≤461 pg/mL; n = 1,576; intermediate 60%), and high AMH (>461 pg/mL; n = 526; highest 20%) groups based on plasma AMH, and associations with reproductive outcomes were tested. Cows with high and intermediate plasma AMH had 1.42- and 1.51-times-greater odds of becoming pregnant within 84 d after the MSD than those with low plasma AMH (90.3 and 90.8 vs. 86.8%, respectively); however, P/AI and pregnancy rate within 21 and 42 d after the MSD did not differ among AMH categories. Plasma AMH was moderately heritable (pedigree heritability of 0.40 ± 0.06 and genomic heritability of 0.45 ± 0.05), and 68 SNP across Bos taurus autosomes 7 and 11 were associated with phenotypic variation in plasma AMH. Out of 68 SNP, 42 were located in a single quantitative trait locus on Bos taurus autosome 11 that harbored 6 previously identified candidate genes (NR5A1, HSPA5, CRB2, DENND1A, NDUFA8, and PTGS) linked to fertility-related phenotypes in dairy cows., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Our objective in this study was to evaluate the reproductive performance of dairy heifers and cows inseminated with fresh or frozen sex-sorted semen (SS) in seasonal-calving pasture-based dairy herds. Ejaculates of 10 Holstein-Friesian bulls were split and processed to provide (1) fresh conventional semen at 3 × 10 6 sperm per straw (CONV); (2) fresh SS at 1 × 10 6 sperm per straw (SS-1M); (3) fresh SS semen at 2 × 10 6 sperm per straw (SS-2M); and (4) frozen SS at 2 × 10 6 sperm per straw (SS-FRZ). Generalized linear mixed models were used to evaluate the effect of semen treatment and other explanatory variables on pregnancy per artificial insemination (P/AI) in heifers (n = 3,214) and lactating cows (n = 5,457). In heifers, P/AI was greater for inseminations with CONV (60.9%) than with SS-FRZ (52.8%) but did not differ from SS-1M (54.2%) or SS-2M (53.5%). Cows inseminated with CONV had greater P/AI (48.0%) than cows inseminated with SS, irrespective of treatment (SS-1M, SS-2M, and S-FROZEN; 37.6, 38.9, and 40.6%, respectively). None of the SS treatments differed from each other with regard to P/AI in either heifers or cows. The relative performance of SS compared with CONV was also examined [i.e., relative P/AI = (SS P/AI)/(CONV P/AI) × 100]. Frozen SS achieved relative P/AI >84%. Bull affected P/AI in both heifers and cows, but no bull by semen treatment interaction was observed. In heifers, P/AI increased with increasing predicted transmitting ability for milk protein percentage. In cows, P/AI increased with increasing Economic Breeding Index (EBI) and with days in milk (DIM) at AI but decreased with increasing EBI milk subindex, parity and with DIM 2 . Cows in parity ≥5 had the lowest P/AI and differed from cows in parities 1, 2, or 3. Dispatch-to-AI interval of fresh semen did not affect P/AI in lactating cows, but a dispatch-to-AI interval by bull interaction was detected whereby P/AI was constant for most bulls but increased with greater dispatch-to-AI intervals for 2 bulls. In conclusion, frozen SS achieved greater P/AI relative to conventional semen than was previously reported in lactating cows. Fresh SS did not achieve greater P/AI than frozen SS, regardless of whether the sperm dose per straw was 1 × 10 6 or 2 × 10 6 . A bull effect for all semen treatments, as well as a dispatch-to-AI interval by bull interaction for fresh semen, highlights the importance of using a large team of bulls for breeding management., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The hypothesis of this study was that cows with good genetic merit for fertility traits (Fert+) would produce oocytes and embryos of greater quality than cows with poor genetic merit for fertility traits (Fert-) and that mRNA expression of candidate genes would reflect the observed differences in quality. The aim of the study, therefore, was to determine the effect of genetic merit for fertility traits on morphological classification and mRNA abundance of key genes in immature oocytes and cumulus cells following ovum pick-up and in embryos following superovulation, artificial insemination (AI), and uterine flushing. In experiment 1, 17 Fert+ and 11 Fert- cows, ranging from 54 to 84 d in milk, were submitted to ovum pick-up on 4 occasions during a 2-wk period. Recovered cumulus-oocyte complexes (COC) were morphologically graded. Oocytes and cumulus cells were separated, and mRNA abundance of genes associated with oocyte developmental competence was measured. There was no effect of genotype on the distribution of COC grades or on the mRNA abundance of the candidate genes in grade 1 COC. In experiment 2, 20 Fert+ and 19 Fert- cows, ranging from 71 to 189 d in milk, were submitted to superovulation and AI. The uteri of cows that responded to the superovulation protocol (17 Fert+ and 16 Fert- cows) were nonsurgically flushed 7 d postovulation. Recovered embryos were morphologically graded, and mRNA abundance of genes associated with embryo development was measured in grade 1 blastocysts. The response to the superovulation protocol was assessed by counting the number of codominant follicles on the day of AI, which was similar for both genotypes (22.0 ± 9.7 and 19.8 ± 8.2 for Fert+ and Fert- cows, respectively). There was no effect of genotype on the proportion of transferable embryos recovered or on the mRNA abundance of the candidate genes tested in the grade 1 blastocysts. Of the total embryos classified as blastocysts, however, the Fert+ cows tended to have a greater proportion of grade 1 blastocysts compared with Fert- cows (90% vs. 64%, respectively). In conclusion, genetic merit for fertility traits had a no effect on mRNA abundance of the candidate genes that were examined in immature oocytes and cumulus cells and in embryos recovered after superovulation. The observed differences in morphological blastocyst quality following superovulation would suggest that the superior reproductive performance of Fert+ cows could arise during the later stages of embryo development from d 7 until maternal recognition of pregnancy., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The evaluation of anogenital distance (AGD), the distance from the center of the anus to base of the clitoris, as a potential fertility trait for genetic selection in dairy cows has generated recent interest. The objectives of this cross-sectional observational study were to (1) characterize the distribution and variability of AGD, (2) determine factors associated with AGD, (3) estimate heritability for AGD, (4) identify single nucleotide polymorphisms (SNP) associated with phenotypic variation of AGD, and (5) validate the relationship between categories of AGD and fertility in Irish Holstein-Friesian cows. Anogenital distance was measured using digital calipers in 1,180 Holstein cows (mean ± standard deviation: 225 ± 79 d in milk) from 10 dairy herds located in Munster, Ireland. In addition, age (yr), weight (kg), height at hip (cm), and body condition score (BCS) at the time of AGD measurement were determined in a subset of 281 cows. Genotype information available from 908 cows was subsequently imputed to the Illumina Bovine High Density BeadChip (Illumina Inc., San Diego, CA) for genome-wide association analysis of phenotypic variation in AGD. Overall, AGD had a normal distribution and high variability (mean ± standard deviation; 119.2 ± 11.6 mm). Anogenital distance was weakly but positively associated with cow age, hip height, and body weight, and negatively associated with BCS; the phenotypic variation in AGD that was explainable by these variables was small (coefficient of determination; R 2 = 0.09, 0.06, 0.10, and 0.02, respectively). The estimated heritability for AGD was 0.37 (standard error of mean ± 0.08). Six SNP of suggestive significance were identified on Bos taurus autosomes 6, 15, 20, and 26; however, none of these SNP was related to previously identified candidate genes for fertility. Cows were categorized into quartiles (Q1; 86 to 111 mm; n = 311, Q2; 112 to 120 mm; n = 330; Q3; 121 to 127 mm; n = 265, and Q4; 128 to 160 mm; n = 274) based on AGD and the association with reproductive outcomes examined (21-d submission rate, pregnancy to first AI, pregnancy rate within 21, 42 and 84-d after the farm mating start date, and number of times bred). None of the reproductive variables differed significantly between AGD categories. In summary, despite identification of high variability and moderate heritability for AGD in Irish Holstein-Friesian cows, reproductive outcomes did not differ between categories of AGD. This latter result differs from our previous finding of an inverse relationship between AGD and pregnancy outcomes in first- and second-parity Canadian Holstein cows, emphasizing the need to test and validate this new phenotype in diverse cow populations., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the effect of progesterone (P4)-based timed artificial insemination (TAI) programs on fertility in seasonal-calving, pasture-based dairy herds. A total of 1,421 lactating dairy cows on 4 spring-calving farms were stratified based on days in milk (DIM) and parity and randomly allocated to 1 of 3 treatments: (1) control: no hormonal treatment; cows inseminated at detected estrus; (2) P4-Ovsynch: cows received a 7-d P4-releasing intravaginal device (PRID Delta; CEVA Santé Animale, Libourne, France) with 100 μg of a gonadotropin-releasing hormone (GnRH) analog (Ovarelin; CEVA Santé Animale) at PRID insertion, a 25-mg injection of PGF 2α (Enzaprost; CEVA Santé Animale) at PRID removal, GnRH at 56 h after device removal and TAI 16 h later; (3) P4-Ovsynch+eCG: the same as P4-Ovsynch, but cows received 500 IU of equine chorionic gonadotropin (eCG; Syncrostim; CEVA Santé Animale) at PRID removal. At 10 d before mating start date (MSD), all cows that were ≥35 DIM were examined by transrectal ultrasound to assess presence or absence of a corpus luteum; body condition score (BCS) was also recorded. Pregnancy diagnosis was performed by transrectal ultrasonography 30 to 35 d after insemination. Overall pregnancy/AI (P/AI) was not different between groups (50.9, 49.8, and 46.3% for control, P4-Ovsynch, and P4-Ovsynch+eCG, respectively) but the 21-d pregnancy rate was increased by the use of synchronization (35.0, 51.7, and 47.2%, respectively). Compared with the control group, synchronization significantly reduced the interval from MSD to conception (34.6, 23.0, and 26.5 d, respectively) and consequently reduced the average days open (98.0, 86.0, and 89.0 d). Across all treatment groups, DIM at the start of synchronization affected P/AI (42.3, 49.5, and 53.9% for <60, 60-80, and >80 DIM, respectively), but neither parity (46.5, 50.4, and 48.4% for parity 1, 2, and ≥3, respectively) nor BCS (44.0, 49.4, and 58.6% for ≤2.50, 2.75-3.25, and ≥3.50, respectively) affected the likelihood of P/AI. Two-way interactions between treatment and DIM, parity, or BCS were not detected. In conclusion, the use of TAI accelerated pregnancy establishment in cows in a pasture-based system by reducing days open, but eCG administration at PRID removal did not affect P/AI., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to (1) evaluate factors associated with variation in circulating anti-Müllerian hormone (AMH) concentrations, (2) establish an optimum AMH threshold predictive of pregnancy to first artificial insemination (P/AI), (3) examine the relationship between AMH and fertility (P/AI, pregnancy loss between 30 and 60 d after artificial insemination, and pregnancy risk up to 250 d postpartum), and (4) identify quantitative trait loci associated with phenotypic variation of AMH concentrations in dairy cows. Serum AMH concentrations (pg/mL) were determined at 7 ± 2.4 d postpartum in 647 lactating Holstein cows (213 primiparous, 434 multiparous) from 1 research and 6 commercial dairy herds in Alberta, Canada. Of these, 589 cows were genotyped on the 26K Bovine BeadChip (Neogen Inc., Lincoln, NE) and subsequently imputed to the Illumina Bovine High Density BeadChip (Illumina, San Diego, CA) for genome-wide association analysis for variation in serum AMH concentrations. Factors associated with variation in serum AMH concentrations and the relationship between categories of AMH and aforementioned fertility outcomes were evaluated only in a subset of 460 cows that had a complete data set available. The overall mean (±standard error of the mean), median, minimum, and maximum AMH concentrations were 191.1 ± 6.3, 151.7, 13.9, and 1,879.0 pg/mL, respectively. The AMH concentrations were not associated with herd, precalving body condition score, postpartum week, and season of sampling; the lactation number, however, had a quadratic relationship with serum AMH concentrations (116.2, 204.9 204.5, and 157.9 pg/mL for first, second, third, and ≥fourth lactation, respectively). The optimum AMH threshold predictive of P/AI could not be established because the receiver operating characteristic curve analysis model was nonsignificant. Categories of AMH [low (<83.0 pg/mL; n = 92), intermediate (≥83.0 to ≤285.0 pg/mL; n = 276), and high (>285.0 pg/mL; n = 92) based on lowest 20%, intermediate 60%, and highest 20% serum AMH) had no associations with P/AI (34, 43, and 40%), pregnancy loss between 30 and 60 d after artificial insemination (20, 12, and 8%), or pregnancy risk up to 250 d postpartum. One candidate gene associated with AMH production [AMH gene on Bos taurus autosome (BTA) 7] and 4 candidate genes related to embryo development (SCAI and PPP6C genes on BTA11 and FGF18 and EEF2K genes on BTA20 and BTA25, respectively) were in linkage disequilibrium with single nucleotide polymorphisms associated with phenotypic variation in serum AMH in dairy cows., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Anogenital distance (AGD) serves as a marker for prenatal androgenization, reproductive development, and fertility in humans and rodents. The primary objectives of this observational study in lactating dairy cows were to (1) characterize the distribution and variability of AGD, (2) determine the relationship among AGD and potential postnatal AGD determinants of age and height, and (3) evaluate the associations between AGD and pregnancy to first artificial insemination (P/AI) and cumulative pregnancy by 250 d in milk (DIM) within parity groups (first, second, and third+ parities). The secondary objective was to evaluate the association between AGD and testosterone concentrations. The AGD (mm), age (yr), and height at hip (cm) at the time of AGD determination, and aforesaid reproductive outcomes were determined in 921 Holstein cows (first, second, and third+ parity; n = 360, 256, and 305, respectively). Plasma concentrations of testosterone were determined in a subset of 93 cows. Overall, AGD had a normal distribution and high variability [mean (±standard deviation); 131.0 ± 12.2 mm], was weakly associated with cow age and height (coefficient of determination = 0.09 and 0.04, respectively), and had an inverse relationship with P/AI in first- and second-parity cows, but not in third+ parity cows. For every 1 mm increase in AGD, the odds of P/AI decreased by 3.4 and 2.4% for first- and second-parity cows, respectively. The optimal AGD threshold to predict probability of P/AI was 127.1 mm for both first- (sensitivity: 66.4; specificity: 56.6%) and second-parity cows (sensitivity: 46.0; specificity: 70.4%). Accordingly, first- and second-parity cows were categorized into either short or long AGD (≤ or >127.1 mm), and associations with reproductive outcomes were evaluated. First-parity cows with long AGD had lower P/AI (30.9 vs. 53.6%) and decreased likelihood (hazard ratio: 0.68) of pregnancy by 250 DIM than those with short AGD. Similarly, second-parity cows with long AGD had reduced P/AI (28.3 vs. 44.4%) and a tendency for decreased likelihood (hazard ratio: 0.76) of pregnancy by 250 DIM than in cows with short AGD. The association between AGD and testosterone was weak and nonsignificant. In summary, AGD in Holstein cows was normally distributed, highly variable, and weakly associated with age and height. Besides, AGD had an inverse relationship with P/AI and cumulative pregnancy by 250 DIM in first- and second-parity cows; however, such a relationship was not evident in older (third+ parity) cows., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

The aims of the present study were to: (1) characterise the metabolome of follicular fluid and serum in dairy cows with similar genetic merit for milk production but with extremes of good (Fert+) or poor (Fert-) genetic merit for fertility; and (2) identify potential biomarkers of dairy cow fertility. Follicular fluid from the first wave dominant follicle and serum were collected on Day 7 of the oestrous cycle. The most pronounced effect of genotype was noted in the serum, where the abundance of total polyunsaturated fatty acids and n-6 polyunsaturated fatty acids was greater in Fert+ cows, and the abundance of total saturated fatty acids was greater in Fert- cows. The abundance of nine fatty acids (arachidic acid, heneicosanoic acid, myristic acid, behenic acid, myristoleic acid, heptadecenoic acid, cis-11-eicosanoic acid, nervonic acid and γ-linolenic acid) in follicular fluid was affected by genotype. Concentrations of cysteine, leucine, ornithine, proline and tyrosine in follicular fluid, and asparagine, creatinine, cysteine, methionine, proline and valine in serum, were also affected by genotype. Receiver operating characteristic curve analysis indicated that the follicular fluid and serum fatty acids and follicular fluid amino acids that were significantly affected by genotype were highly predictive of fertility genotype.

Profitable milk production in dairy cows requires good reproductive performance. Calving interval is a trait used to measure reproductive efficiency. Herein we used a novel lactating Holstein cow model of fertility that displayed genetic and phenotypic divergence in calving interval, a trait used to define reproductive performance using a national breeding index in Ireland. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility (Fert+; n=7) or very poor genetic merit for fertility (Fert-; n=6). We tested the hypothesis that Fert+ cows would have a corresponding detectable difference in endometrial gene expression compared with the Fert- cows. To do this, we sequenced the transcriptome of endometrial biopsies collected on Day 7 of the oestrous cycle (non-pregnant). This is an important stage for uterine remodelling and initiation of histotroph secretion. Significant differential expression (false discovery rate-adjusted P<0.1) of 403 genes between Fert+ and Fert- cows was found. A novel network-based functional analysis highlighted 123 genes from three physiologically relevant networks of the endometrium: (1) actin and cytoskeletal components; (2) immune function; and (3) ion transportation. In particular, our results indicate an overall downregulation of inflammation-related genes and an upregulation of multiple ion transporters and gated-voltage channels and cytoskeletal genes in Fert+ cows. These three topics, which are discussed in terms of the uterus and in the context of fertility, provide molecular evidence for an association between gene expression in the uterine environment and genetic merit for fertility in dairy cows.

Background: The transition between pregnancy and lactation is a major physiological change for dairy cows. Complex systemic and local processes involving regulation of energy balance, galactopoiesis, utilisation of body reserves, insulin resistance, resumption of oestrous cyclicity and involution of the uterus can affect animal productivity and hence farm profitability. Here we used an established Holstein dairy cow model of fertility that displayed genetic and phenotypic divergence in calving interval. Cows had similar genetic merit for milk production traits, but either very good genetic merit for fertility traits ('Fert+'; n = 8) or very poor genetic merit for fertility traits ('Fert-'; n = 8). We used RNA sequencing to investigate gene expression profiles in both liver and muscle tissue biopsies at three distinct time-points: late pregnancy, early lactation and mid lactation (-18, 1 and 147 days relative to parturition, respectively)., Results: We found 807 and 815 unique genes to be differentially expressed in at least one time-point in liver and muscle respectively, of which 79 % and 83 % were only found in a single time-point; 40 and 41 genes were found differentially expressed at every time-point indicating possible systemic or chronic dysregulation. Functional annotation of all differentially expressed genes highlighted two physiological processes that were impacted at every time-point in the study, These were immune and inflammation, and metabolic, lipid and carbohydrate-binding., Conclusion: These pathways have previously been identified by other researchers. We show that several specific genes which are differentially regulated, including IGF-1, might impact dairy fertility. We postulate that an increased burden of reactive oxidation species, coupled with a chronic inflammatory state, might reduce dairy cow fertility in our model.

Despite the importance of fertility in humans and livestock, there has been little success dissecting the genetic basis of fertility. Our hypothesis was that genes differentially expressed in the endometrium and corpus luteum on Day 13 of the estrous cycle between cows with either good or poor genetic merit for fertility would be enriched for genetic variants associated with fertility. We combined a unique genetic model of fertility (cattle that have been selected for high and low fertility and show substantial difference in fertility) with gene expression data from these cattle and genome-wide association study (GWAS) results in ∼20,000 cattle to identify quantitative trait loci (QTL) regions and sequence variants associated with genetic variation in fertility. Two hundred and forty-five QTL regions and 17 sequence variants associated primarily with prostaglandin F2alpha, steroidogenesis, mRNA processing, energy status, and immune-related processes were identified. Ninety-three of the QTL regions were validated by two independent GWAS, with signals for fertility detected primarily on chromosomes 18, 5, 7, 8, and 29. Plausible causative mutations were identified, including one missense variant significantly associated with fertility and predicted to affect the protein function of EIF4EBP3. The results of this study enhance our understanding of 1) the contribution of the endometrium and corpus luteum transcriptome to phenotypic fertility differences and 2) the genetic architecture of fertility in dairy cattle. Including these variants in predictions of genomic breeding values may improve the rate of genetic gain for this critical trait., (© 2016 by the Society for the Study of Reproduction, Inc.)

This study investigated the factors affecting circulating progesterone (P4) concentrations in cows with similar genetic merit for milk production traits, but with extremes of good (Fert+) or poor (Fert-) genetic merit for fertility traits. Study 1: 28 cows were enrolled in an ovulation synchronization protocol at 61±13 (±standard deviation) days postpartum, and data are presented for 13 Fert+ and 9 Fert- cows that remained in the study. Progesterone concentrations were determined from d 0 to 9 (d 0=estrus) and on d 7, corpus luteum (CL) volume and blood flow area (BFA) were measured by B-mode and Doppler ultrasonography, respectively. Cows were administered PGF2α on d 7 in the p.m. and d 8 in the a.m. to regress the CL, and 2 controlled internal drug release devices were inserted per vaginum on d 8 in the a.m. Liver biopsies were collected on d 9 and hepatic mRNA abundance of genes involved in P4 catabolism was determined. On d 10, the controlled internal drug release inserts were removed and frequent blood samples were collected to measure the rate of decline in circulating P4. The Fert+ cows tended to have greater dry matter intake compared with Fert- cows (+0.79kg of dry matter/d), but similar milk production (29.82kg/d). After synchronized ovulation, the rate of increase in circulating P4 concentrations was greater in Fert+ cows compared with Fert- cows. No effect of genotype on CL volume was detected, but BFA was 42% greater in Fert+ cows compared with Fert- cows. The Fert- cows had greater mRNA abundance of cytochrome P450, family 3, subfamily A (CYP3A) compared with Fert+ cows, but the mRNA abundance of aldo-keto reductase family 1, member C1 (AKR1C1), AKR1C3, AKR1C4, and cytochrome P450, family 2, subfamily C (CYP2C) were similar. The half-life and metabolic clearance rate of P4 were similar in Fert+ cows and Fert- cows. Study 2: 23 cows were enrolled in an ovulation synchronization protocol at 55±7 (±standard deviation) d postpartum, and data are presented for 13 Fert+ and 8 Fert- cows that remained in the study. On d 4, 7, 10, and 13 (d 0=estrus), CL volume and BFA were measured as in study 1. Progesterone concentrations were measured from d 1 to 13. Corpus luteum volume was 41% greater in Fert+ cows compared with Fert- cows but no effect of genotype on BFA was detected. Mean circulating P4 concentrations were 79% greater in Fert+ cows compared with Fert- cows. Milk yield was similar in both genotypes. The results indicate that greater circulating P4 concentrations were primarily due to greater CL P4 synthetic capacity rather than differences in P4 clearance in this lactating cow genetic model of fertility., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to monitor the dry matter intake (DMI), metabolic status, uterine health, and resumption of cyclicity in cows with similar genetic merit for milk production traits but with either good (Fert+) or poor genetic merit (Fert-) for fertility traits. Twenty-six cows were enrolled in the study and data are reported for 15 Fert+ and 10 Fert- cows that completed the study. All cows received a total mixed ration diet during early lactation and were turned out to pasture in late spring. Dry matter intake was recorded daily from wk -2 to 5 relative to parturition. Blood metabolites and metabolic hormones were measured from wk -2 to 8 relative to parturition. Milk production, body condition score, and body weight until wk 35 of lactation are reported. To monitor uterine health, vaginal mucus was scored weekly on a scale of 0 (no pus) to 3 (≥ 50% pus) from parturition to wk 8 and uterine polymorphonuclear neutrophil count was measured at wk 3 and 6 postpartum. Prepartum DMI was similar between genotypes, but Fert+ cows had significantly greater DMI than Fert- cows (19.7 vs. 16.8 kg of dry matter/d) during the postpartum period. Energy balance at wk 1 was significantly greater in Fert+ cows than in Fert- cows [2.3 vs. -1.12 unité fourragère lait (UFL)/d]. The Fert+ cows had significantly greater daily milk solids production (1.89 vs. 1.74 kg/d) and tended to have greater daily milk yield (24.2 vs. 22.3 kg/d). The Fert+ cows had significantly greater mean circulating insulin-like growth factor-I (102.62 vs. 56.85 ng/mL) and tended to have greater mean circulating insulin (3.25 vs. 2.62 μIU/mL) compared with Fert- cows from wk -2 to 8 relative to parturition. Mean circulating glucose (3.40 vs. 3.01 mmol/L) concentrations were significantly greater in Fert+ cows compared with Fert- cows from wk -2 to 3 relative to parturition. The Fert+ cows maintained significantly greater mean body condition score throughout lactation compared with Fert- cows (2.98 vs. 2.74 units). Moreover, Fert+ cows had better uterine health compared with Fert- cows, as evidenced by lower weekly vaginal mucus scores from wk 2 to 6 postpartum and, based on uterine cytology, smaller proportions were classified as having endometritis at wk 3 (0.42 vs. 0.78) and 6 (0.25 vs. 0.75). Also, a significantly greater proportion of Fert+ cows had resumed cyclicity by wk 6 postpartum (0.86 vs. 0.20) compared with Fert- cows. Hence, we report for the first time that genetic merit for fertility traits is associated with postpartum uterine health status. Superior uterine health and earlier resumption of cyclicity may be mediated through differences in DMI, energy balance, insulin, insulin-like growth factor-I, and body condition score profiles. Importantly, phenotypic improvement in fertility traits was achieved without antagonizing milk production., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The advent of AI has markedly improved the production potential of dairy cows in all systems of production and transformed the dairy industry in many countries. Unfortunately, for many years breeding objectives focused solely on milk production. This resulted in a major decline in genetic merit for fertility traits. In recent years, the underlying physiological mechanisms responsible for this decline have started to be unravelled. It is apparent that poor genetic merit for fertility traits is associated with multiple defects across a range of organs and tissues that are antagonistic to achieving satisfactory fertility performance. The principal defects include excessive mobilisation of body condition score, unfavourable metabolic status, delayed resumption of cyclicity, increased incidence of endometritis, dysfunctional oestrus expression and inadequate luteal phase progesterone concentrations. On a positive note, it is possible to identify sires that combine good milk production traits with good fertility traits. Sire genetic merit for daughter fertility traits is improving rapidly in the dairy breeds, including the Holstein. With advances in animal breeding, especially genomic technologies, to identify superior sires, genetic merit for fertility traits can be improved much more quickly than they initially declined.

The objective of this study was to characterize the estrous cycle of cows with similar proportions of Holstein genetics, similar genetic merit for milk production traits, but with good (Fert+) or poor (Fert-) genetic merit for fertility traits. In total, 37 lactating cows were enrolled on a protocol to synchronize estrus. Nineteen Fert+ and 12 Fert- cows that successfully ovulated a dominant follicle and established a corpus luteum underwent daily transrectal ultrasonography. Blood sampling was carried out at 8-h intervals from d 0 to 6 and from d 15 to ovulation, and once daily from d 7 to 15. Blood samples were analyzed for progesterone, estradiol, follicle stimulating hormone, and luteinizing hormone. Estrus behavior was recorded using neck activity collars and mounting pads. The Fert+ cows tended to have fewer follicular waves (2.2 vs. 2.7) and had a shorter estrous cycle (21.0 vs. 25.1 d) than Fert- cows. We observed no effect of genotype on day of first-wave emergence or day of first-wave dominant follicle peak diameter, but the peak diameter of the first-wave dominant follicle tended to be larger in Fert- cows. During the first 13 d of the cycle, Fert+ cows developed a corpus luteum that was 16% larger than that in Fert- cows. Circulating progesterone concentrations were 34% greater in Fert+ than in Fert- cows (5.15 vs. 3.84ng/mL, respectively) from d 5 to 13. During the final follicular wave, the interval from preovulatory follicle emergence to ovulation and the interval from preovulatory follicle dominance to ovulation were similar in both genotypes. Maximum preovulatory follicle diameter was larger in Fert+ than Fert- cows (17.9 vs. 16.8mm, respectively); however, circulating concentrations of estradiol were not different between genotypes. A greater proportion of Fert- cows ovulated to a silent heat than Fert+ cows (22 vs. 2%, respectively). Of cows that showed behavioral estrus, Fert+ cows had 41% greater mean activity count; however, no difference was seen in mounting behavior between genotypes. These results demonstrate, for the first time, that genetic merit for fertility has pronounced effects on corpus luteum development, progesterone concentration, preovulatory follicle diameter, and behavioral estrus., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to characterize the circulating concentrations of insulin-like growth factor-I (IGF-I) and the hepatic expression of key genes regulating the somatotropic axis in cows divergent in genetic merit for fertility traits but with similar genetic merit for milk production traits. A total of 11 cows with good genetic merit for fertility (Fert+) and 12 cows with poor genetic merit for fertility (Fert-) underwent liver biopsy by percutaneous punch technique on d 20 (±6.7 d) prepartum and on d 2 (±1.5 d), d 58 (±3.7 d), d 145 (±13 d), and d 245 (±17.1 d) postpartum. Total RNA was isolated and the mRNA expression of growth hormone receptor (GHR 1A and GHRtot), IGF-I, janus tyrosine kinase 2 (JAK2), signal transducer and activator of transcription 5B (STAT5B), suppressor of cytokine signaling 3 (SOCS-3), acid-labile subunit (ALS), and IGF-binding proteins (IGFBP1 to IGFBP6) were measured by real-time quantitative PCR. During lactation, the circulating concentrations of IGF-I were 34% greater in Fert+ cows. The Fert+ cows had increased mean expression of IGF-I mRNA during the study; however, the difference in IGF-I mRNA abundance between Fert+ and Fert- cows was most pronounced at d 145 and 245. The expression of IGFBP3 and ALS transcript was similar in Fert+ and Fert- cows for the duration of the study. The Fert- cows, however, had greater expression of IGFBP2, IGFBP4, IGFBP5, and IGFBP6. Genotype had no effect on mRNA abundance of GHR 1A, STAT5B, JAK2, or SOCS-3. Genetic merit for fertility traits affects hepatic expression of key genes of the somatotropic axis regulating the synthesis, bioavailability, and stability of circulating IGF-I., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The total number of ovarian follicles ≥ 3mm in diameter (antral follicle count, AFC) during follicular waves varies among cattle of similar age, but AFC is highly repeatable within individuals. We hypothesized that lower AFC could be associated with reduced fertility in cattle. The AFC was assessed by ultrasonography for 2 d consecutively during the first wave of follicular growth of the estrous cycle, 4.6±1.43 d (mean ± SD) after estrus, in 306 Holstein-Friesian dairy cows approximately 70 d postpartum. Cows were classified into 3 groups based on AFC: low (AFC ≤15), intermediate (AFC=16 to 24), and high (AFC ≥25). During the cycle in which AFC was assessed and in subsequent cycles, cows were artificially inseminated (AI) following detection of estrus, and pregnancy status was assessed using ultrasonography. Cows with high AFC had 3.34 times greater odds of being pregnant at the end of the breeding season compared with cows with low AFC; the odds of a successful pregnancy at first service were 1.75 times greater in the intermediate compared with the low group. The predicted probability of a successful pregnancy by the end of the breeding period (length of breeding season was 86±16.3 d) was 94, 88, and 84% for the high, intermediate, and low AFC groups, respectively. No difference was evident among groups in 21-d submission rate (proportion of all cows detected in estrus and submitted for AI in the first 21 d of the breeding season), but the interval from calving to conception was shorter in the high (109.5±5.1 d) versus low (117.1±4 d) group, and animals with intermediate AFC received fewer services during the breeding season (2.3±0.1) compared with animals with low AFC (2.7±0.1). Lactating cows with ≤15 ovarian follicles have lower reproductive performance compared with cows with higher numbers of follicles, but the existence of a positive association between high numbers of ovarian follicles and fertility is yet to be established., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of the present study was to characterize the phenotypic performance of cows with similar proportions of Holstein genetics, similar genetic merit for milk production traits, but with good (Fert+) or poor (Fert-) genetic merit for fertility traits. Specifically, we tested the hypothesis that cows with a negative estimated breeding value for calving interval would have superior fertility performance and would have detectable differences in body reserve mobilization and circulating concentrations of metabolic hormones and metabolites compared with cows that had a positive estimated breeding value for calving interval. For the duration of the study, cows were managed identically as a single herd in a typical grass-based, spring-calving production system. A total of 80 lactation records were available from 26 Fert+ and 26 Fert- cows over 2 consecutive years (2008 and 2009). During yr 1, cows were monitored during a 20-wk breeding season to evaluate reproductive performance. Milk production, body condition score (scale 1 to 5), body weight, grass dry matter intake, energy balance, and metabolic hormone and metabolite data were collected during both years. The Fert+ cows had greater daily milk yield (19.5 vs. 18.7 kg/d), shorter interval from calving to conception (85.6 vs. 113.8 d), and fewer services per cow (1.78 vs. 2.83). No difference between groups in grass dry matter intake, energy balance, or body weight was observed. The Fert+ cows maintained greater BCS during mid (2.84 vs. 2.74 units) and late lactation (2.82 vs. 2.73 units). Circulating concentrations of insulin-like growth factor-I were greater throughout the gestation-lactation cycle in Fert+ cows (148.3 vs. 128.2 ng/mL). The Fert+ cows also had greater circulating concentrations of insulin during the first 4 wk of lactation (1.71 vs. 1.24 μIU/mL). Analysis of records from national herd data verified the association between genetic merit for fertility traits and phenotypic reproductive performance; Fert+ cows (n = 2,436) required 11.1 d less to recalve than did Fert- cows (n = 1,388), and the percentage of cows that successfully calved for the second time within 365 and 400 d of the first calving was 8 and 13% greater for Fert+ compared with Fert- cows, respectively. These results demonstrate that genetic merit for fertility traits had a pronounced effect on reproductive efficiency, BCS profiles, and circulating concentrations of insulin-like growth factor-I., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the effect of two different rumen-protected fat supplements, on reproductive performance and milk production, in grass-based spring calving cows. Two hundred and one Holstein-Friesian cows with an average lactation number of 3.6 (20% first lactation, 16% second lactation and 64% third lactation or greater) were grouped into blocks of three on the basis of calving date, lactation number and previous lactation milk yield for cows of second lactation or greater and on the basis of calving date for first lactation animals. From within-blocks individual animals were assigned at random, within 10 days post-calving, to one of the following three treatments: (1) Megalac Plus 3% (MP; 0.4kg/day, containing Ca salt of palm fatty acids and Ca salt of methionine hydroxy analogue), (2) Megapro Gold (MPG; 1.5kg/day, containing Ca salt of palm fatty acids, extracted rapeseed meal and whey permeate), and (3) Control (C; unsupplemented). Cows were supplemented for on average 103 days (range 54-134 days). The average milk yield over the first 12 weeks of lactation was higher (P<0.05) for both fat supplements compared to C and was higher for MP compared to C over the full lactation. Both supplements reduced (P<0.05) milk protein concentration over the first 6 weeks of lactation. MPG increased (P<0.05) conception rate to first service compared to C. Conception rate to first service was similar (P=0.14) on MP compared to C. For pregnancy to second service, C had a higher (P<0.05) conception rate than MP. There were no significant differences between treatments in overall pregnancy rate, services per conception, number of cows served in the first 3 weeks of the breeding season or the 6-weeks in-calf rate. Comparing the combined fat treatments to C resulted in a higher (P<0.05) conception rate to first service for the fat treatments but no significant difference in overall pregnancy rate. In conclusion, fat supplements increased conception rate to first service but did not significantly affect the proportion of cows pregnant at the end of the breeding season.