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Prenatal stress (PNS) and early life adversity have been linked to epigenetic changes in the nervous, immune, and endocrine systems in various species. Previously, we reported that PNS calves had greater serum concentrations of ACTH and cortisol, were more temperamental, and had differential methylation of leukocyte DNA. The purpose of this study was to determine whether prenatal transportation stress differentially affected gene expression in the adrenal gland of calves. Mature Brahman cows inseminated to a single Brahman sire were assigned to either Control (n = 35; not transported) or PNS (n = 37; 2 h of transportation at 60, 80, 100, 120, and 140 ± 5 d of gestation) group. From some of these cows, 8 Control and 8 PNS bull calves were humanely euthanized at 25 ± 2 d of age. Adrenal glands were obtained, separated into the cortical (AC) and medullary (AM) components, placed into cryovials, snap frozen in liquid nitrogen, and stored at -80°C. Frozen samples (200 mg) were submitted to Novogene Corporation for RNA sequencing analysis on an Illumina Novaseq 6000 platform to generate 150 bp paired-end reads. The reference genome was Bos taurus ARS-UCD1.2. The DESeq2 R package was used for differential gene expression analysis (DEG) and DEGs (P ≤ 0.05, log2FC ≥ 1) were evaluated for gene ontology (GO) subclass terms and Kyoto encyclopedia of genes and genomes (KEGG) enrichment pathways. For the AC DEG comparison, a total of 899 genes were identified, with 641 upregulated and 258 downregulated in PNS calves. The AC DEGs were in the cellular component, molecular function and biological process GO subclasses related to circadian rhythm, lymphocyte proliferation, cytokine regulation, muscle development, and lipid metabolism. The KEGG enrichment analysis identified nitrogen metabolism, cytokine signaling, and circadian rhythm pathways associated with DEG of the AC. For the AM DEG comparison, a total of 1,245 genes were identified, with 745 upregulated and 500 downregulated in the PNS calves. The AM DEGs were in GO subclasses related to skeletal muscle development, antigen processing, and neural crest development. The KEGG enrichment analysis identified cell adhesion, viral infection, cytokine signaling, and amphetamine pathways associated with DEG of the AM. These early results suggest that prenatal stress differentially affects expression of genes of the adrenal cortex and adrenal medulla, which may affect health and growth of calves. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in females of reproductive age. Hypersecretion of luteinizing hormone (LH), partly due to increased pituitary sensitivity to gonadotrophin-releasing hormone (GnRH), is a significant cause of infertility in women with PCOS. Moreover, obesity amplifies the severity of reproductive dysfunction in PCOS. In sheep, testosterone (T) excess during gestational days (GD) 30 to 90 results in GnRH-mediated LH hypersecretion and recapitulates the PCOS phenotype. This study investigated 1) if midgestation (GD 60 to 90) is the susceptibility window for programming pituitary hypersensitivity to GnRH, and 2) the contribution of postnatal obesity in modulating LH responsiveness to GnRH. Suffolk ewes received T propionate (T; 100 mg i.m.) or corn oil (C; vehicle) twice weekly from GD 60 to 90 (term = 147 d). At 5 mo of age, T lambs were assigned randomly to either a maintenance (100% of NRC requirements) or overfed diet (130% of NRC requirements), and Control lambs were fed the maintenance diet. During the anestrous period (late summer), ewes (n = 8/group; ~17 mo of age) received a GnRH bolus injection (2 ng/kg) intravenously every 1.5 h and blood samples were collected at 15-min intervals for a 6-h period. Despite animals being in seasonal anestrous, few endogenous LH pulses were evident during the 6 h-sampling period. To avoid confounding, only clear responses to GnRH challenge that occurred within 15 to 45 min after each GnRH injection were considered for further analyses. Mean number of exogenous GnRH-induced LH responses that met these criteria did not differ between groups and averaged 1.81 ± 0.27 pulses/animal. The parameters of these GnRH-induced responses were analyzed as one-way ANOVA with Tukey's HSD post-hoc analysis. Mean LH pulse peak was greater (P < 0.05) in T overfed ewes (4.59 ± 0.49 ng/mL) compared with T maintenance (2.19 ± 0.61 ng/mL) and Control ewes (2.58 ± 0.53 ng/mL). Additionally, amplitude of LH pulses was greater (P < 0.05) in T overfed ewes (2.66 ± 0.39 ng/mL) compared with T maintenance (1.03 ± 0.48 ng/mL) and tended (P = 0.089) to be greater in T overfed compared with Control ewes (1.41 ± 0.42 ng/mL). LH pulse peak and amplitude in T maintenance did not differ from Control ewes. In conclusion, failure of GD 60 to 90 T treatment to increase GnRH responsiveness as opposed to our earlier finding of increased responsiveness in GD 30 to 90 T-treaded sheep indicates that the susceptibility window for programming pituitary hypersensitivity to GnRH lies between GD 30 to 60. Postnatal obesity may act as an independent activational signal in amplifying the pituitary sensitivity to GnRH in female sheep. This premise is supported by observations that obesity exacerbates pituitarymediated LH hypersecretion in women with PCOS. Research support: NIH-NICHD (R01HD099096). [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women of reproductive age. Women with PCOS exhibit reduced sensitivity of the GnRH neuronal system to the inhibitory effects of both progesterone and estradiol. Additionally, obesity amplifies the severity of the PCOS phenotype. In sheep, testosterone (T) excess during gestational days (GD) 30-90 and 60-90 reduces neuroendocrine sensitivity to the progesterone negative feedback and recapitulates the PCOS phenotype. This study investigated the contribution of postnatal obesity in amplifying or mitigating the effects of midgestational T excess in disrupting the responsiveness to progesterone negative feedback in sheep. Suffolk ewes received T propionate (T; 100 mg i.m.) or corn oil (CO; vehicle) twice weekly from GD 60-90 (term = 147 d). At 5 mo of age, F1 T lambs were assigned randomly to either a maintenance (100% of NRC requirements) or overfed diet (130% of NRC requirements) and control lambs were fed the maintenance diet. At 22 mo of age, F1 ewes (n = 8/group) were synchronized with two injections of PGF2α 11 d apart. After the second PGF2α administration, blood samples were collected daily for 14 d and progesterone concentrations were determined via radioimmunoassay. Ewes that were confirmed to be cycling and in the mid-luteal phase based on progesterone concentrations (progesterone = 1 ng/ml on day 10 and = 0.5 ng/ml on days 8-9 and 11-12) were used for LH pulse characterization. On day 10 after PGF2α synchronization (mid-luteal phase), blood samples were collected every 15 min for 6 h to characterize LH pulsatile secretion via radioimmunoassay. Data were analyzed as one-way ANOVA with Tukey's HSD post-hoc analysis. Frequency of LH pulses was greater (P < 0.05) in T maintenance (3.75 ± 0.41 pulses/6h) and T overfed ewes (3.50 ± 0.34 pulses/6h) compared with controls (2.00 ± 0.37 pulses/6 h). Luteinizing hormone pulse amplitude was greater (P < 0.05) in T overfed (2.03 ± 0.15 ng/mL) compared with T maintenance (1.44 ± 0.17 ng/mL), but not to controls (1.74 ± 0.21 ng/mL). Also, average LH concentration was greater (P < 0.05) in T overfed (2.03 ± 0.24 ng/mL), but not T maintenance (1.31 ± 0.35 ng/mL), compared with controls (0.93 ± 0.30 ng/mLl). In conclusion, these findings demonstrate the activational role of postnatal obesity in amplifying prenatal T-induced alterations in tonic LH secretion during progesterone negative feedback. The activational effect of postnatal obesity in increasing LH secretion and consequently thecal androgen production is likely a contributor to the severity of hyperandrogenic status in women with PCOS. Research support: NIH-NICHD (R01HD099096). [ABSTRACT FROM AUTHOR]

Approximately 5 million beef heifers enter the U.S. cow herd annually, and their lifetime productivity is largely dependent upon their ability to attain puberty and produce a calf by 24 mo of age. However, a considerable proportion of heifers within existing U.S. production systems fail to achieve these goals, particularly in southern regions where Bos indicusinfluenced cattle predominate. Consequently, managerial approaches are needed that employ nutritional programming of the reproductive neuroendocrine axis, while minimizing feeding costs and optimizing the consistent attainment of puberty by approximately 14 mo of age. Our previous research has clearly demonstrated that increased BW gain between 4 and 8 mo of age facilitates pubertal development by programming hypothalamic centers that regulate gonadotropin releasing-hormone (GnRH) secretion. Among the different metabolic hormones, leptin has a critical role in conveying nutritional information to the hypothalamus and controlling puberty. Two hypothalamic neuronal populations that express the orexigenic peptide neuropeptide Y (NPY) and the anorexigenic peptide alpha melanocyte-stimulating hormone (aMSH; a product of the POMC gene) are key components of afferent pathways that convey inhibitory (NPY) and excitatory (aMSH) inputs to GnRH and kisspeptin neurons. Our studies have demonstrated that short-term increases in dietary energy intake after early weaning at 4 mo of age result in epigenetic, structural, and functional modifications in these hypothalamic pathways to promote high-frequency, episodic release of GnRH and luteinizing hormone. However, integrating the foundational knowledge of metabolic imprinting of the brain for early puberty with issues related to lifetime performance is complex. One approach has been to employ a novel stair-step nutritional regimen involving alternating periods of dietary energy-restriction and re-feeding during juvenile development. This approach is designed to support early onset of puberty by imprinting functional alterations in the hypothalamus during key periods of brain development while optimizing other aspects of growth and performance. Finally, while several key processes of fetal brain development occur during late gestation, neither maternal undernutrition (BCS 3.0-3.5) nor maternal obesity (BCS 7.5-8.0) during the last two trimesters of gestation impacted the organization of hypothalamic neurocircuitries controlling GnRH/LH secretion or age at puberty in the heifer offspring. Collectively, these results indicate that the adult reproductive phenotype in Bos indicus-influenced females is resilient to significant degrees of nutritional stress imposed during prenatal development, particularly if early gestation (first trimester) is avoided. These findings are in contrast with reports in Bos taurus females in which late gestation nutritional extremes result in delayed puberty in heifer offspring, suggesting that potential genotype-specific differences may exist. Research support: USDA-NIFA-AFRI (2018-67015-27595 and 2021-67015-33676). [ABSTRACT FROM AUTHOR]

It is well known that pre- and post-natal stressors can impact livestock phenotype and performance. However, less is known about the molecular mechanisms responsible for the changes observed in individuals exposed to stress. A proposed mechanism is epigenetic modifications, such as DNA methylation (DNAm). Epigenetic marks are considered a bridge between the environment and genetics because the marks shift in response to environmental stimuli. Stress induced alterations of DNAm can result in changes in gene expression which could be the driver behind altered phenotype. "Omic" technologies have allowed the study of how DNAm patterns change in response to stressors in livestock species. Stressors such as weaning, transportation, and heat stress have altered DNAm patterns. These changes in methylation patterns have been associated with changes in immune function, growth, and behavior. Prenatal stressors have also modified DNAm patterns within the offspring, with some differences persisting later in life. These stress induced DNAm alterations can be transgenerational, potentially affecting livestock productivity and health over multiple generations. Not all alterations are negative; certain stress-induced modifications could allow animals to adapt better to stressors and changing conditions. These marks may indicate exposure of the animal to stress and the possible long-term effects on productivity. There is potential for using methylation patterns as a noninvasive way to monitor stress levels and assess animal welfare. Understanding how the methylome responds to stressors and how it contributes to performance will be beneficial for future selection decisions. More research is needed to identify management practices that might mitigate the negative impacts of stress induced DNAm changes and how the industry can take advantage of the role DNAm has in adapting to stressors and new environments. The epigenome will likely play a critical role in the livestock industry's future as the climate shifts and consumer demands focus more on animal welfare. [ABSTRACT FROM AUTHOR]

Angus x Hereford heifers (n = 50) were randomly assigned to bahiagrass pastures treated with biosolids varying in mineral content and evaluated for mineral status, with special attention to Cu. Biosolids and [NH.sub.4][NO.sub.3] were all applied at the rate of either 179 kg N/ha (X) or twice this (2X). Fertilizer was applied to .81-ha pastures for the following treatments: 1) Baltimore biosolids (1X = 179 kg N/ha); 2) Baltimore biosolids (2X = 358 kg N/ha); 3) Tampa biosolids (1X = 179 kg N/ha); 4) Tampa biosolids (2X = 358 kg N/ha); or 5) control [NH.sub.4][NO.sub.3] (1X = 179 kg N/ha) applied at two times. Pastures were divided into five blocks with each treatment represented once in each block. Copper loads varied from 8.8 to 42.2 kg/ha, and Mo loads varied from .27 to 1.11 kg/ha. Heifers (two per pasture) grazed their assigned pastures exclusively for 176 d. Liver biopsies were taken from all animals at d 1, 99, and 176, and blood samples on d 1, 50, 99, 135, and 176. Liver and plasma were analyzed for selected mineral contents, and blood was analyzed for hemoglobin and hematocrit. Experimental animals were generally low in mineral status when assigned to pastures and deficient in Se and P. By d 50, plasma Ca, Mg, Se, P, and Zn were adequate for all treatments. Plasma Cu declined (P [is less than] .03) for all treatments from d 50 to 176. Plasma Cu reflected depleted liver Cu storage, with the two Tampa and highest Baltimore treatment means lower in plasma Cu than the control at 176 d. Liver Fe concentrations were adequate for all treatments, and Mo concentrations ([is less than] 2.18 mg/kg) did not approach levels indicative of toxicity. Liver Cu declined (P [is less than] .05) with time for all treatments. By d 99, animals receiving the two Baltimore treatments and the lowest Tampa application rate had lower (P [is less than] .05) liver Cu than the control, and all treatments were lower at 176 d. The decline of animal Cu status (liver and plasma) reflects the low Cu status of bahiagrass and the possibility of high forage S (.30 to .47%) interfering with Cu metabolism. Forage Mo was low but was slightly higher in biosolids-treated pastures. High levels of biosolids applications to bahiagrass pastures were not detrimental to mineral status except Cu, which had a tendency to decline in plasma and for all biosolids treatments declined in liver. Key Words: Biosolids, Cattle, Fertilizers, Minerals, Pastures

Telomeres are comprised of G-rich nucleotide sequences (5'-TTAGGG-3') at the chromosome termini that are responsible for protecting chromosomes; however, attrition of these sequences has been observed due to aging and stress. The purpose of this study was to compare telomere length (TL) in control and prenatally stressed (PNS) calves. Mature Brahman cows inseminated to a single Brahman sire in 2018 were assigned to be either Control (n=35; not transported) or PNS (n=37; 2 h of transportation at 60, 80, 100, 120, and 140±5 d of gestation). Jugular blood samples were obtained by venipuncture from 10 Control (5 bulls and 5 heifers) and 10 PNS (5 bulls and 5 heifers) calves at 25±2 d of age. Peripheral leukocytes were isolated and genomic DNA was extracted utilizing silicone membrane spin column kits. The relative quantity of telomere products, which is proportional to the average TL, was determined by multiplex quantitative PCR analysis using the ratio of bovine telomere and ß-globulin DNA (T/S ratio). An absolute standard of bovine telomere (1012-107 dilution series) and ß-globulin (109-104 dilution series) genes was utilized to produce relative copy number. All samples were processed in triplicate and samples were included if the triplicate Cq difference was less than 0.25 cycles. Data were analyzed using ANOVA. TL differed by sex (P< 0.03; bulls 11,959±211; heifers 12,850±366) and treatment (P< 0.02; Control 12,895±278; PNS 11,913±303). There was not an interaction of sex and treatment (P >0.43) although TL of Control heifers (13,482±396) exceeded the TL of PNS bulls (11,609±348). These observations of fewer copies of telomere sequences suggest an influence of sex on TL within 1 month of age; and, that prenatal transportation stress may increase attrition of telomeres in cattle. [ABSTRACT FROM AUTHOR]

Prenatal testosterone excess causes reproductive perturbations in sheep that recapitulate those seen in women with polycystic ovary syndrome (PCOS). Obesity has a significant role in the development and severity of the PCOS phenotype. Our objective was to investigate the effects of testosterone excess from gestational days (GD) 60-90 (unlike the GD 30-90 model, these animals are not virilized) and postnatal body weight (BW) gain on puberty in firstgeneration ewe lambs. Pregnant Suffolk ewes received testosterone propionate (T; 100 mg) or corn oil (C) i.m. twice weekly from GD 60-90 (term=147d). Ewe lambs were weaned ~3 mo of age. Control and T lambs were assigned to gain either 0.3 kg/d (C and T-maintenance) or 0.4 kg/d (T-overfed). Maintenance diet was designed to promote optimal growth without excess fat deposition. Overfed ration was designed to achieve a BW ~30% above that of maintenance. Progesterone concentrations were measured via radioimmunoassay in blood samples collected twice weekly from ewe lambs (n=15/group) during the first breeding season. Puberty was defined as when progesterone concentrations were < 0.5 ng/mL for four consecutive samples followed by three consecutive samples =0.5 ng/mL. Six animals (C, n=1; T-maintenance, n=3; T-overfed, n=2) did not attain puberty during the study and puberty was assigned as last day of sampling. Average daily gain was not different among treatments (C, 0.23±0.02kg; T-maintenance, 0.25±0.01kg; T-overfed, 0.27±0.02kg). Age at puberty did not differ between groups (C, 274.6±9.9d; T-maintenance, 270.0±11.3d; T-overfed, 266.0±10.2d). Similarly, BW at puberty did not differ across treatments (C, 50.44±2.2kg; T-maintenance, 52.5±2.4kg; T-overfed, 57.3±2.5kg). In conclusion, unlike GD 30-90 exposure which advanced puberty, GD 60-90 exposure did not affect age and BW at puberty in ewe lambs. Collectively, these studies suggest that GD 30-60 is a critical developmental window in which prenatal testosterone excess advances puberty in female sheep. Research support: NIH-NICHD (R01HD099096). [ABSTRACT FROM AUTHOR]

Objectives were to test the hypothesis that nutritional extremes during prenatal development interact with postnatal nutrition during the juvenile period of heifers to impact KNDy neuron responsiveness to a neurokinin B (NKB) agonist (Senktide) during progesterone dominance. Heifers were selected from a larger population programmed nutritionally using a 3x2 factorial arrangement of pre- and post-natal diets. Bos indicus-influenced cows (n = 95) were fed to achieve body condition scores (BCS; 1-9 scale) of 3-3.5 (L; thin), 5.5-6 (M; moderate), or 7.5-8 (H; obese) by the onset of the third trimester and maintained thereafter. Heifer offspring were weaned at 3-3.5 mo of age and assigned to either a low-(L; 0.5 kg/day) or high-gain (H; 1 kg/day) diet until 8 mo of age, then fed a common diet until puberty. For the current experiment, heifers (n = 18; 6/group) representing LL, MH, and HH combinations were ovariectomized postpubertally (17.1 mo of age) and received estradiol (E2) replacement to maintain basal E2 concentrations at 2-4 pg/mL. To achieve progesterone dominance, 3 CIDR devices were placed intravaginally 6 days prior to the initiation of Senktide challenge. Heifers were sampled for a 4.5-h period and received intravenous injections of saline or Senktide (14.8 ug/kg I.V.) at 0, 90, and 180 min. Jugular blood samples were collected at 10-min intervals for radioimmunoassay of LH. Irrespective of Senktide treatment, heifers in the MH group had greater pulse amplitudes (P = 0.016) and mean concentrations (P < 0.0001) of LH compared with both the HH and LL groups. Senktide treatment increased (P = 0.003) concentrations of LH compared with saline in all groups; however, the response to Senktide was greatest in the MH group compared with HH and LL. Pre- and postnatal nutritional extremes appear to interact to impact KNDy neuron responsiveness to NKB receptor signaling in heifers. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the ovarian response of Brahman cows submitted to two different estrus synchronization protocols and to determine the estrus response and ovulation time. A total of 153 Brahman cows were randomly assigned to receive one of the following estrus synchronization protocols: 1) CIDR insert and an injection of prostaglandin F2a (25 mg, PGF) on Day -5 and CIDR removal with PGF on Day 0 (CIDR5; n = 77); 2) CIDR insert on Day -12 and an injection of PGF on Day -12, Day -5 and Day 0 upon CIDR removal (CIDR12; n = 76). Estrotect breeding indicator patches were placed on Day 0 and cows were artificially inseminated (AI) 12h after estrus detection; cows not detected in estrus after 96h received TAI coupled with 100 µg of GnRH. Ovarian dynamics were observed during the protocol and follicular diameter were measured every 12h after AI until ovulation. Cows synchronized with CIDR12 had increased follicular diameter (CIDR5, 10.19 ± 0.51 vs. CIDR12, 13.12 ± 0.52 mm; P = 0.01) and decreased serum concentrations of progesterone (CIDR5, 1.68 ± 0.12 vs. CIDR12, 0.81 ± 0.12 ng/ml; P < 0.01) at CIDR removal. The percentage of cows exhibiting estrus did not differ between treatments (CIDR5, 66.2 vs. CIDR12, 64.5%; P = 0.25). No difference was observed in ovulation rate (CIDR5, 94.1 vs. CIDR12, 94.1%; P = 0.6). Time of estrus expression and ovulation time after CIDR removal did not differ (CIDR5, 59.9 ± 2.3 vs. CIDR12, 61.5 ± 2.3h; P = 0.71 and CIDR5, 88.1 ± 2.6 vs. CIDR12, 90.9 ± 2.6h; P = 0.75; respectively). In conclusion, extended length of CIDR with additional PGF increased follicular diameter and decreased concentrations of progesterone but did not influence estrus response and ovulation time in Brahman cows. [ABSTRACT FROM AUTHOR]

Objectives were to test the hypotheses that nutritional extremes during prenatal development interact with postnatal nutrition during the juvenile period of heifers to impact 1) tonic secretion of gonadotropins, and 2) estradiol-17β (E2) negative and positive feedback responsiveness in adulthood. Heifers were selected from a larger population programmed nutritionally using a 3 x 2 factorial arrangement of pre- and postnatal diets. Beginning at 90 days of pregnancy, Bos indicusinfluenced cows (n = 95) were fed to achieve body condition scores (BCS; 1-9 scale) of 3-3.5 (L; thin), 5.5-6 (M; moderate), or 7.5-8 (H; obese) by onset of the third trimester and maintained thereafter. Heifer offspring were weaned at 3-3.5 months of age and assigned to either a low- (L; 0.5 kg/day) or high-gain (H; 1.0 kg/day) diet until 8 mo. of age, then fed a common diet until puberty. Heifers (n = 18; 6/grp) representing HH, MH and LL combinations were ovariectomized postpubertally (17.1 mo. of age) and received E2 replacement. In Exp. 1, blood samples were collected at 10-min intervals to evaluate pulsatile secretion of LH and FSH for 5.5 hours. In Exp. 2, heifers received E2 (2.4 ug/kg I.M.), with blood sampling at 30-min to 1-h intervals for 30 h. Heifers in the MH (1.25 ± 0.11 ng/mL) group tended (P < 0.09) to have greater LH pulse amplitude compared to HH (0.91 ± 0.14 ng/mL) and LL (0.96 ± 0.09 ng/mL); otherwise, frequency, amplitude, and mean concentrations of LH and FSH did not differ among groups. Exogenous E2 (Exp. 2) suppressed (P < 0.0001) mean plasma concentrations of LH and FSH equally among groups, then stimulated equivalent surges of LH beginning at 14 ± 0.02 h, with only two FSH surges detected. Neither pre- nor postnatal nutrition affected E2 negative or positive feedback in this study. [ABSTRACT FROM AUTHOR]

Links between nutrition and reproductive success in heifers have been demonstrated; however, achieving a high plane of nutrition is costly, and reproductive success remains uncertain, making heifer development expensive and risky. Development could be optimized by using nutritionally efficient strategies to manage plane of nutrition without negatively impacting reproduction. At an average age of 340 d, 85 heifers (209 kg) were randomly assigned to 1 of 3 treatments: high (H, n = 29), programmed to gain 0.92 kg/d, medium (M, n = 28), 0.45 kg/d and low (L, n = 28), 0 kg/d from d 0 to d 49 (P1). Heifers were then programmed to gain 1.36 kg/d from d 50 to d 90 (P2). Heifers were individually fed a common diet (42% cracked corn, 26% DDG, 26% alfalfa hay, and 6% molasses; 15% CP, 1.2 Mcal NEg/kg), using a calan-gate system, at varying levels to achieve programmed gain. Weekly BW and blood samples were collected. Digestibility was measured beginning d 41 (P1) and d 83 (P2). All heifers were synchronized beginning d 90 using the Bee Synch protocol for fixed-time AI on d 98, followed by 56 d exposure to bulls. Pregnancy rates were determined on d 154. Gain differed between treatments in P1 (P < 0.01); M- and L-fed heifers exceeded programmed gain by 0.16 and 0.37 kg/d respectively (H = 0.83, M = 0.61, L = 0.37 kg/d). No treatment effect on gain (P = 0.07) was observed in P2 (H = 1.31, M = 1.41, L = 1.37 kg/d). Digestion in P1 differed (P = 0.01) between heifers fed H (86.2% DM) and L (88.7% DM); no differences (P = 0.23) were observed in P2. Total ADG and input costs were different among treatments (P < 0.01). The cost of development on the M or L treatments was $10 or $23 less per heifer, respectively, than H ($95.35). Body weight and number pubertal on d 90 were not different (P ≥ 0.10). Pregnancy rates on d 154 were 79, 96, and 82% for H, M, and L respectively, but were not different (P = 0.21). Developing heifers on a lower plane of nutrition decreased cost per pregnancy without apparent negative effects on reproductive success. The M strategy was the optimal development program based on cost per pregnancy; however, additional research is needed to confirm the effects on reproductive outcomes. [ABSTRACT FROM AUTHOR]

According to the USDA National Agricultural Statistics Service, approximately 5.1 million beef heifers enter the U.S. cow herd annually (2013 -2017). With inventory averaging 30.5 million cows, this annual rate of entry represents nearly 17% of the total beef cow population. Lifetime productivity of these replacements is heavily- dependent upon their ability to reach sexual maturity, to conceive early during their first breeding season as yearlings, and to calve the first time by approximately 24 mo of age. Yet, a relatively small percentage of cattlemen nutritionally pre-program their heifers as herd replacements. Therefore, approaches are needed that facilitate nutritional imprinting of the reproductive neuroendocrine system during early calfhood, while minimizing feeding costs, promoting effective mammary gland development, optimizing the consistent establishment of estrous cycles by 12 to 14 mo of age, but avoiding a high incidence of precocious puberty. It is now clear that the interval between 4 and 9 mo of age (juvenile period) represents a critical period for metabolically programming the neuroendocrine axis to achieve early and targeted reproductive maturation. By focusing on nutritionally-mediated changes during this time, we have been able to characterize a number of structural and functional modifications in hypothalamic pathways that respond to high-concentrate/high gain diets. Alterations include modifications in morphological development of neuronal pathways that regulate the gonadotropin- releasing hormone (GnRH) pulse generator, changes in factors that facilitate the ability of leptin to cross the blood-brain barrier, alterations in gene expression in specific hypothalamic nuclei, and modifications in DNA methylation patterns. However, integrating the interdependent issues of metabolic imprinting of the brain for pre-programmed puberty with issues related to lifetime performance is complex. One approach has been to employ a modified version of a novel stair-step nutritional regimen involving alternating periods of dietary energy-restriction and re-feeding phases. This approach is designed to support early onset of puberty by imprinting genomic, biochemical and morphologic alterations in the hypothalamus while avoiding morphometric changes that can impair long-term productivity. To this end, we are also learning that nutritional epigenetic effects programmed during the postnatal period interact with those occurring prenatally. These interactions may induce structural and functional changes in hypothalamic neuronal pathways that persist long after pubertal maturation, are imprinted in the genome, and are apt to influence physiological performance and fertility throughout adulthood. [ABSTRACT FROM AUTHOR]