Induced Physical Distension of Rat Mammary Glands Accelerates the Onset of Apoptosis and Involution

Phyn, C.V.C.; Davis, Stephen R.; Dobson, Joanne; Stelwagen, K.; Singh, Kuljeet

doi:10.4172/2576-1471.1000160

Cited by 4 publications

(4 citation statements)

References 57 publications

(97 reference statements)

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“…In support of a role for mechanotransduction, mammary cell stretch in vitro was associated with the induction of apoptotic pathways (Quaglino et al, 2009). Furthermore, studies in vivo demonstrated that acute physical distension of rat mammary glands with sucrose solution accelerated the induction of apoptosis, upregulation of the apoptotic factor activated signal transducer and activator of transcription-3, and loss of the extracellular matrix factor β1-integrin and tight junction factor occludin (Phyn et al, 2007). Recently, the distribution and morphological changes in the mechanosensors primary cilia during lactation and involution implicate a role in initiating involution of the mammary gland (Millier et al, 2013).…”

Section: Discussionmentioning

confidence: 96%

The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows

Singh

Swanson

et al. 2015

Journal of Dairy Science

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In dairy cows, extended periods of nonmilking results in reduced milk secretion, modifications in milk composition, and eventually involution of the mammary glands. The aim of this study was to determine the effect of extended nonmilking periods on the recovery of milk yield and composition, and levels of prolactin and insulin-like growth factor-I in pasture-fed cows after resuming milking. Pasture-fed, primiparous, nonpregnant, Friesian dairy cows at mid lactation (mean ± standard deviation, 97 ± 2d in milk, 14.0 ± 2.5 L/d) were divided into 3 groups (n=6 per group). The cows were subjected to nonmilking periods of 7, 14, or 28d. Twice-daily milking was resumed for 7d following the nonmilking periods. Milk yield recoveries at the end of the 7-d remilking period were 91, 51, and 29% for the 7, 14, and 28-d nonmilked groups, respectively. The somatic cell count declined to less than 400,000 cells/mL by d 3 and 6 of remilking for the 7- and 14-d-nonmilked groups, respectively, but remained greater than 800,000 cells/mL in the 28-d-nonmilked group through the 7-d remilking period. By d 7 of remilking, the somatic cell count for the 7-d-nonmilked group was not different from pretrial values. Upon remilking, the milk fat content returned to pretrial values for the 7- and 14-d-nonmilked groups, although it remained lower than pretrial for the 28-d-nonmilked group. All 3 nonmilked groups had a higher milk protein content following 7d of remilking, compared with pretrial values. The lactose content returned to pretrial values for the 7-d-nonmilked group but remained lower for the 14- and 28-d-nonmilked groups. Circulating prolactin concentrations increased once remilking was resumed, compared with the pretrial and nonmilking periods. Prolactin concentrations did not majorly differ between the groups, with the levels upon 7d of remilking remaining higher than the pretrial concentrations and the nonmilked periods. Plasma concentrations of insulin-like growth factor-I increased during the nonmilking period and were greater in all 3 nonmilked groups on d 1 of remilking than pretrial values and returned to pretrial concentrations following remilking for the 7-d-nonmilked group, whereas the 14- and 28-d-nonmilked groups remained higher than the pretrial values. These data indicate that the process of involution is fully reversed after remilking following 7d of milk stasis but more extended periods of nonmilking prevent the complete recovery of lactation. However, even after 28d of milk stasis, the milk synthesis capacity of the mammary gland could still be partially recovered.

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Section: Discussionmentioning

confidence: 96%

The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows

Singh

Swanson

et al. 2015

Journal of Dairy Science

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“…Physical distension of the mammary gland, which results in changes in cell shape (Richardson, ), may also play a role by activating mechanotransduction pathways, leading to a loss of TJ integrity and cell‐ECM survival signaling (Davis et al, ; Stelwagen, ). In support of mechanotransduction, mammary cell stretch in vitro induces apoptotic pathways (Quaglino et al, ) and in vivo accelerates the induction of apoptosis and loss of the ECM factor β1‐integrin and the TJ protein occludin (Phyn et al, ). Furthermore, primary cilia, key signalling organelles for sensing biochemical and biophysical extracellular stimuli, have been implicated in initiating involution of the mammary gland (Millier et al, ; Biet et al, ).…”

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confidence: 99%

Tight Junction Protein Abundance and Apoptosis During Involution of Rat Mammary Glands

Phyn

Stelwagen

Davis

et al. 2017

Journal Cellular Physiology

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To examine tight junction protein abundance and apoptosis of epithelial cells at the onset of involution in rodent mammary glands, milk accumulation and mammary engorgement were induced by teat-sealing with an adhesive for 0, 6, 12, 18, 24, and 36 h (n = 6 per group) at peak lactation. In non-sealed control glands, histological analysis confirmed a lactating phenotype, indicating suckling by pups throughout the experiment. In contrast, alveoli of teat-sealed glands were distended within 6 h, with maximal luminal size observed by 12 h of non-suckling. By 18 h following teat-sealing, an involuting phenotype was observed, indicated by alveolar lumina engorged with milk vesicles and increased leukocytes. Relative to non-sealed glands, mammary apoptosis was increased in engorged glands 18 h following teat-sealing. The abundance of ZO-1 and occludin proteins was decreased in engorged glands by 12 and 18 h, respectively, following teat-sealing. In contrast, the claudin-1 22 kDa band was increased by 6 h and peaked at 12-18 h, whereas the 28 kDa band declined by 36 h, relative to controls. There were no temporal changes in ZO-1, occludin, and claudin-1 22 kDa proteins within control glands, although there were minor differences in claudin-1 28 kDa. These data indicate that intramammary milk accumulation due to cessation of milk removal is associated with mammary apoptosis. The apoptotic event is preceded by a rapid loss of abundance of ZO-1, occludin and an initial increase in claudin-1. The loss of cell-cell communication may initiate involution and apoptosis of mammary epithelial cells and is a localized intramammary event, occurring only in non-suckled glands. J. Cell. Physiol. 232: 2075-2082, 2017. © 2016 Wiley Periodicals, Inc.

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“…In support, cell-cell communication (Cooper et al, 2004), cell-extracellular matrix communication (Singh et al, 2005), and the primary cilia of mechanosensors (Millier et al, 2013;Biet et al, 2016) were disrupted following milk engorgement at the onset of involution of the bovine mammary gland. Furthermore, acute physical distension of rat mammary glands with sucrose solution in vivo accelerated the onset of apoptosis of MEC, disruption of cell-cell and cell-extracellular matrix communication, and activation of STAT3 (Phyn et al, 2007). In bovine, this treatment suppressed milk secretion (Stelwagen et al, 1998) and milk protein gene expression (Biet et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial heterogeneity in milk and immune-related gene expression during mammary gland involution in dairy cows

Singh

Phyn

Reinsch

et al. 2017

Journal of Dairy Science

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The aim of this study was to investigate heterogeneity in tissue morphology, milk protein and immune-related gene expression, and apoptosis of epithelial cells in the lactating and involuting mammary glands of the dairy cow. Mammary tissue from different regions of the gland (alveolar, cisternal, and peripheral) was collected postmortem from nonpregnant, pasture-fed, Holstein-Friesian primiparous cows in mid-lactation that were killed at different time points postmilking: 0, 6, 12, 18, 24, 36, and 72 h (n = 6 per time point). The CSN1NS1 and LALBA mRNA was decreased in alveolar, cisternal, and peripheral tissue by 12 to 36 h postmilking. In contrast, lactoferrin (LF) and mammary serum amyloid A3 (M-SAA3) mRNA was increased in these regions by 36 to 72 h. During lactation, more variability was present in gene expression in alveolar tissue between cows and between quarters within a cow, than within quarters. Histological analysis indicated the alveolar tissue from lactating cows was mostly uniform in structure; however, in situ hybridization indicated that although most of the alveolar tissue expressed milk proteins, the level of expression varied within and between alveoli. This heterogeneity became more pronounced with involution and with increasing regions of alveoli expressing lactoferrin, indicating that alveoli enter involution asynchronously. The peripheral and cisternal tissue had more variability in gene expression between cows compared with the alveolar tissue. The M-SAA3 signal was more intense in the cisternal tissue and less intense than the peripheral compartment compared with LF particularly in the earlier time points. In addition, between cows within the later time points, differences were observed in tissue morphology, the levels of milk protein and immune-related gene expression, and phosphorylated signal transducer and activator of transcription (STAT) 5-P and STAT3-P proteins, and degree of apoptosis, indicating that involution of the mammary gland occurs at different rates between cows. Understanding the mechanisms initiating the process of involution of the mammary gland provides an opportunity for enhancing milk production of the dairy cow.

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Induced Physical Distension of Rat Mammary Glands Accelerates the Onset of Apoptosis and Involution

Cited by 4 publications

References 57 publications

The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows

The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows

Tight Junction Protein Abundance and Apoptosis During Involution of Rat Mammary Glands

Temporal and spatial heterogeneity in milk and immune-related gene expression during mammary gland involution in dairy cows

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