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A dynamic mammary gland model describing colostrum immunoglobulin transfer and milk production in lactating sows.

ABSTRACT: The physiology of the sow mammary gland is qualitatively well described and understood. However, the quantitative effect of various biological mechanisms contributing to the synthesis of colostrum and milk is lacking and more complicated to obtain. The objective of this study was to integrate physiological and empirical knowledge of the production of colostrum and milk in a dynamic model of a single sow mammary gland to understand and quantify parameters controlling mammary gland output. In 1983, Heather Neal and John Thornley published a model of the mammary gland in cattle, which was used as a starting point for the development of this model. The original cattle model was reparameterized, modified, and extended to describe the production of milk by the sow mammary gland during lactation and the prepartum production of colostrum as the combined output of immunoglobulins (Ig) and milk. Initially, the model was reparameterized to simulate milk synthesis potential of a single gland by considering biological characteristics and empirical estimations of sows and piglets. Secondly, the model was modified to simulate more accurately the responses to changes in milk removal rates. This was done by linking the ejectable milk storage capacity to the number of secretory cells rather than being constant throughout lactation. Finally, the model was extended to include the prepartum synthesis of milk and the kinetics of Ig into and out of the mammary gland. A progressive capacity of secretory cells to synthesize milk was used to differentiate the time between the onset of milk synthesis and Ig transfer. Changes in maximum milk removal rate, duration of milk ejection, and nursing interval exerted a great impact on the modeled milk output. Changes by ±60% in one of these parameters were capable of increasing milk output by 28% to 39% during the first 4 wk in lactation compared with the reference parameterization. This suggests that the ability of the piglet to remove milk from the gland exerts a key control on milk synthesis during lactation. Modeling colostrum as the combined output of Ig and milk allowed to represent the rapid decline in Ig concentration observed during the first hours after farrowing. In conclusion, biological and empirical knowledge was integrated into a model of the sow mammary gland and constitutes a simple approach to explore in which conditions and to what extent individual parameters influence Ig kinetics and milk production.

SUBMITTER: Krogh U

PROVIDER: S-EPMC7887553 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMicroRNAs (miRNAs) have a great influence on various physiological functions. A lot of high-throughput sequencing (HTS) research on miRNAs has been executed in the caprine mammary gland at different lactation periods (common milk lactation and dry period), but little is known about differentially expressed miRNAs in the caprine mammary gland of colostrum and peak lactation periods.ResultThis study identified 131 differentially expressed miRNAs (P?<?0.05 and log2 colostrum normalized expression (NE)/peak lactation NE?>?1 or log2 colostrum NE/peak lactation NE?<?-1), including 57 known miRNAs and 74 potential novel miRNAs in the colostrum and peak lactation libraries. In addition, compared with differentially expressed miRNAs in the peak lactation period, 45 miRNAs in the colostrum lactation period were remarkably upregulated, whereas 86 miRNAs were markedly downregulated (P?<?0.05 and log2 colostrum NE/peak lactation NE?>?1 or log2 colostrum NE/peak lactation NE?<?-1). The expressions of 10 randomly selected miRNAs was analyzed through stem-loop real-time quantitative PCR (RT-qPCR). Their expression patterns were the same with Solexa sequencing results. Pathway analysis suggested that oestrogen, endocrine, adipocytokine, oxytocin and MAPK signalling pathways act on the development of mammary gland and milk secretion importantly. In addition, the miRNA-target-network showed that the bta-miR-574 could influence the development of mammary gland and lactation by leptin receptor (LEPR), which was in the adipocytokine signalling pathway. Chr5_3880_mature regulated mammary gland development and lactation through Serine/threonine-protein phosphatase (PPP1CA), which was in the oxytocin signalling pathway.ConclusionsOur finding suggested that the profiles of miRNAs were related to the physiological functions of mammary gland in the colostrum and peak lactation periods. The biological features of these miRNAs may help to clarify the molecular mechanisms of lactation and the development of caprine mammary gland.

Project description:To investigate the role of glucose in regulating milk fatty acid synthesis, 6 lactating Guanzhong dairy goats were infused with 0, 60, or 100 g/d glucose via the external pubic artery in a 3 × 3 repeated Latin square experiment. A concomitant in vitro experiment was conducted to investigate possible mechanisms whereby glucose regulates milk fatty acid synthesis. RNA sequencing was used for cellular transcriptome analysis. Drugs, MK-2206, rapamycin, and dorsomorphin were used to block cellular mammalian AMP-activated protein kinase (AMPK), AKT serine/threonine kinase 1, and mechanistic target of rapamycin kinase signaling pathways, respectively. Carbohydrate response element binding protein (ChREBP) was knockdown and overexpressed to investigate its role in regulating milk fatty acid synthesis in mammary epithelial cells. Glucose infusion linearly elevated the concentration of C8:0 (P = 0.039) and C10:0 (P = 0.041) in milk fat while it linearly decreased (P = 0.049) that of C16:0. This result was in agreement with the upregulation of genes related to de novo synthesis of fatty acids and lipid droplet formation, including adipose differentiation-related protein, butyrophilin subfamily 1 member A1, fatty acid synthase (FASN) and ChREBP. Their expression increased (P < 0.05) linearly in the lactating goat mammary gland. In vitro, glucose linearly stimulated the expression of genes related to de novo synthesis of fatty acids and cellular triacylglycerol in cultured mammary epithelial cells. RNA sequencing and inhibition studies revealed that glucose induced transcriptomic changes increasing lipogenic pathways, with AMPK responding to glucose by controlling ChREBP and FASN. Knockdown and overexpression of ChREBP highlighted its essential role in lipogenesis. The knockdown and overexpression of ChREBP protein also revealed an essential role in regulating the de novo synthesis of fatty acids. Collectively, our data highlight that glucose supplementation promotes de novo fatty acid synthesis via the AMPK-ChREBP axis, hence increasing milk fat yield in the goat mammary gland. Results from the current study provide possible strategies to manipulate the fatty acid composition as well as improve ruminant milk quality.

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A dynamic mammary gland model describing colostrum immunoglobulin transfer and milk production in lactating sows.

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