Project description:BACKGROUND: The lactating mammary gland responds to changes in milking frequency by modulating milk production. This response is locally regulated and, in dairy cows, the udder is particularly sensitive during early lactation. Relative to cows milked twice-daily throughout lactation, those milked four-times-daily for just the first 3 weeks of lactation produce more milk throughout that lactation. We hypothesized that the milk yield response would be associated with increased mammary cell turnover and changes in gene expression during frequent milking and persisting thereafter. Cows were assigned to unilateral frequent milking (UFM; left udder halves milked twice-daily; right udder halves milked four-times daily) on days 1 to 21 of lactation, followed by twice-daily milking for the remainder of lactation. Relative to udder halves milked twice-daily, those milked four-times produced more milk during UFM; the difference in milk yield declined acutely upon cessation of UFM after day 21, but remained significantly elevated thereafter. We obtained mammary biopsies from both udder halves on days 21, 23, and 40 of lactation. RESULTS: Mammary cell proliferation and apoptosis were not affected by milking frequency. We identified 75 genes that were differentially expressed between paired udder halves on day 21 but exhibited a reversal of differential expression on day 23. Among those genes, we identified four clusters characterized by similar temporal patterns of differential expression. Two clusters (11 genes) were positively correlated with changes in milk yield and were differentially expressed on day 21 of lactation only, indicating involvement in the initial milk yield response. Two other clusters (64 genes) were negatively correlated with changes in milk yield. Twenty-nine of the 75 genes were also differentially expressed on day 40 of lactation. CONCLUSIONS: Changes in milking frequency during early lactation did not alter mammary cell population dynamics, but were associated with coordinated changes in mammary expression of at least 75 genes. Twenty-nine of those genes were differentially expressed 19 days after cessation of treatment, implicating them in the persistent milk yield response. We conclude that we have identified a novel transcriptional signature that may mediate the adaptive response to changes in milking frequency.

Project description:Four-times daily milking during the first 3 weeks of lactation elicits an increase in milk yield, which persists through late lactation even after twice-daily milking is imposed. We hypothesized that this milk yield response would be associated with changes in mammary proliferation, apoptosis, and gene expression, which would persist throughout lactation. Six multiparous cows were assigned to unilateral frequent milking (UFM; twice daily milking of the left udder half (2X), four-times daily milking of the right udder half (4X)) on days 1 to 21 of lactation, followed by 2X thereafter. Udder halves initially milked 4X produced more milk than those milked 2X during, and after UFM treatment, through 180 days in milk (DIM). To determine the mechanisms involved in the persistent milk yield response, we obtained mammary biopsies from both udder halves at 21, 23, and 40 DIM. Rates of [3H]-thymidine incorporation into DNA in vitro and mammary cell apoptosis were not affected by UFM or DIM. Using Affymetrix GeneChipM-BM-. Bovine Genome Arrays, we determined that the differential expression (4X vs. 2X) of 18 genes was significantly affected by DIM. Within the group of 18 differentially expressed genes, we identified a cluster of 15 genes with a similar temporal pattern of differential expression. Nine of the genes in the cluster remained differentially expressed at 40 DIM, indicating that they may be involved in the persistent milk yield response. Among the genes in the cluster were chitinase 3-like (CHI3L)-1, clusterin, early growth response (EGR)-1, and sex determining region Y-box (SOX)-4. These genes have been associated with mammary development, differentiation and remodeling; all of which may be functionally related to the increase in milk yield. We conclude that frequent milking during early lactation does not alter mammary growth but is associated with changes in mammary expression of 18 genes. Future experiments will determine the function of these genes in the mammary gland, and will clarify their role in the autocrine regulation of milk production and long-term alteration of mammary function. 36 samples from 6 cows; 3 timepoints

Project description:BACKGROUND: The lactating mammary gland responds to changes in milking frequency by modulating milk production. This response is locally regulated and, in dairy cows, the udder is particularly sensitive during early lactation. Relative to cows milked twice-daily throughout lactation, those milked four-times-daily for just the first 3 weeks of lactation produce more milk throughout that lactation. We hypothesized that the milk yield response would be associated with increased mammary cell turnover and changes in gene expression during frequent milking and persisting thereafter. Cows were assigned to unilateral frequent milking (UFM; left udder halves milked twice-daily; right udder halves milked four-times daily) on days 1 to 21 of lactation, followed by twice-daily milking for the remainder of lactation. Relative to udder halves milked twice-daily, those milked four-times produced more milk during UFM; the difference in milk yield declined acutely upon cessation of UFM after day 21, but remained significantly elevated thereafter. We obtained mammary biopsies from both udder halves on days 21, 23, and 40 of lactation. RESULTS: Mammary cell proliferation and apoptosis were not affected by milking frequency. We identified 75 genes that were differentially expressed between paired udder halves on day 21 but exhibited a reversal of differential expression on day 23. Among those genes, we identified four clusters characterized by similar temporal patterns of differential expression. Two clusters (11 genes) were positively correlated with changes in milk yield and were differentially expressed on day 21 of lactation only, indicating involvement in the initial milk yield response. Two other clusters (64 genes) were negatively correlated with changes in milk yield. Twenty-nine of the 75 genes were also differentially expressed on day 40 of lactation. CONCLUSIONS: Changes in milking frequency during early lactation did not alter mammary cell population dynamics, but were associated with coordinated changes in mammary expression of at least 75 genes. Twenty-nine of those genes were differentially expressed 19 days after cessation of treatment, implicating them in the persistent milk yield response. We conclude that we have identified a novel transcriptional signature that may mediate the adaptive response to changes in milking frequency.

Project description:Systemic inflammation is common in early lactation dairy cows and is associated with decreased milk production. The Scutellaria baicalensis plant contains flavonoids with anti-inflammatory and anti-oxidative properties, which may counteract the inflammatory state in early lactation dairy cows. The objective of this experiment was to determine whether Scutellaria baicalensis extract (SBE), a source of bioactive flavonoids, would alter the adaptation to lactation. Multiparous Holstein cows (n = 122) were used in a randomized block design to determine the effect of short-term and long-term postpartum administration of SBE on 305-d milk yield, 120-d milk component yield, and early lactation milk markers of inflammation and metabolic function. Treatments were 1) control, 2) short term (5-d) administration of the SBE (SBE5), and 3) long term (60-d) administration of the SBE (SBE60). Treatments were included in a treatment pellet that was identical to a control pellet in ingredient source and composition except for the extract (10 g/d SBE providing 3.3 g/d of the flavonoid baicalin), both provided via an automated milking system beginning on d 1 of lactation. Milk samples were collected on d 1, 3, and once during d 5-12 of lactation, followed by weekly sampling until 120 days in milk (DIM). Milk samples collected in the first 2 wk were used for biomarker analysis (haptoglobin, ?-hydroxybutyrate [BHB], and glucose-6-phosphate [G6P]), and all samples were used for composition analysis. Cows were body condition scored every 2 wk prepartum and postpartum. Milk production, programmed pellet allocation, and actual provision of both pelleted feeds were recorded daily. Treatment effects were evaluated by contrasts between control and SBE5 and control and SBE60 for both the treatment (TP; wk 1-9) and carryover periods (CP; wk 10-37). Total pellet offered was greater for SBE60 in both the TP (P < 0.01) and CP (P = 0.02) but was not different for SBE5 during either period (P ? 0.13). No treatment effects were observed for body condition score (BCS), milk haptoglobin, BHB, or G6P. SBE5 did not alter milk yield or milk components. SBE60 increased whole-lactation milk yield by 1,419 kg (13%; P = 0.03). SBE60 increased milk lactose and fat yields (P ? 0.04) and tended to increase milk protein yield (P = 0.09) during TP, and each increased during CP (P ? 0.04). Somatic cell count decreased by 10% in SBE60 during TP (P = 0.02) but not CP (P = 0.13). Mastitis incidence tended to differ by treatment, being lesser for both SBE5 and SBE60 vs. control (14 and 15% vs. 33%). SBE supplementation did not impact time to pregnancy or hazard of leaving the herd. In conclusion, despite no detected treatment effects on BCS or milk biomarkers of inflammation and metabolic status, supplementation of postpartum dairy cows with Scutellaria baicalensis extract for 60 d was effective at increasing whole lactation milk yield.

Dataset Information

Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal.

Publications

Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal.

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