Regulation of cell number in the mammary gland by controlling the exfoliation process in milk in ruminants

Hervé, Lucile; Quesnel, Hélène; Lollivier, Vanessa; Boutinaud, Marion

doi:10.3168/jds.2015-9964

Cited by 45 publications

(35 citation statements)

References 70 publications

(96 reference statements)

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“…The disruption of mammary epithelial integrity was accompanied by an increase in MEC concentration in mammary secretions, suggesting an enhancement of MEC shedding from the alveolar structure. Increased MEC shedding with a concomitant disruption of mammary epithelial integrity was reported previously during lactation (Herve et al, 2016). In the mouse mammary gland, numerous MEC are rapidly observed in alveolar lumen within 24 h until 4 d of mammary involution (Monks and Henson, 2009;Watson and Kreuzaler, 2011).…”

supporting

confidence: 54%

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Boutinaud

Isaka

Gandemer

et al. 2017

Journal of Dairy Science

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The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d −6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d −6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na + and K + ) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na + and K + concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single injection of cabergoline after the last milking would facilitate drying-off by enhancing mammary gland involution.

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supporting

confidence: 54%

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Boutinaud

Isaka

Gandemer

et al. 2017

Journal of Dairy Science

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“…In the present study, the decrease in milk yield induced by feed restriction was associated with a 65% increase in the MEC exfoliation rate. In dairy ruminants, lower milk yield has been previously associated with a higher MEC exfoliation rate in response to various physiological, environmental, or breeding factors (Herve et al, 2016). Moreover, the proportion of viable MEC exfoliated into milk tended to be higher in feed-restricted cows than in control cows.…”

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confidence: 94%

“…In dairy ruminants, a high MEC exfoliation rate has been associated with disruption of the mammary epithelium (Herve et al, 2016). In the present study, integrity of the mammary epithelium was assessed by measuring plasma lactose concentrations and the Na + :K + ratio in milk.…”

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confidence: 95%

“…The milk yield of dairy cows is determined by the secretory activity of mammary epithelial cells (MEC, i.e., cells that synthesize milk; Capuco et al, 2003;Boutinaud et al, 2004a) and by the number of these cells, which is regulated by the balance between cell proliferation and cell death by apoptosis (Knight, 2000;2671Capuco et al, 2003. Moreover, the exfoliation of MEC, defined as the shedding of MEC from the mammary epithelium into milk, has recently been shown to participate in the regulation of MEC number (Herve et al, 2016). Feed restriction has shown contradictory effects on these factors.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, the decreased number of MEC in the mammary gland has been attributed to a decrease in the cell proliferation rate without variation in the apoptosis rate (Nørgaard et al, 2005) but is also ascribed to an increase in the apoptosis rate without variation in the cell proliferation rate (Dessauge et al, 2011). The effect of feed restriction on the MEC exfoliation rate has been investigated in only one study, which showed no variation in the daily rate of MEC exfoliation in response to feed restriction (Herve et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Milk yield loss in response to feed restriction is associated with mammary epithelial cell exfoliation in dairy cows

Hervé

Quesnel

Veron

et al. 2019

Journal of Dairy Science

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In dairy cows, feed restriction is known to decrease milk yield by reducing the number of mammary epithelial cells (MEC) in the udder through a shift in the MEC proliferation-apoptosis balance, by reducing the metabolic activity of MEC, or both. The exfoliation of MEC from the mammary epithelium into milk is another process that may participate in regulating the number of MEC during feed restriction. The aim of the present study was to clarify the mechanisms that underlie the milk yield loss induced by feed restriction. Nineteen Holstein dairy cows producing 40.0 ± 0.7 kg/d at 77 ± 5 d in milk were divided into a control group (n = 9) and a feed-restricted group (n = 10). Ad libitum dry matter intake (DMI) was recorded during a pre-experimental period of 2 wk. For 29 d (period 1), cows were fed either 100 (control) or 80% (feedrestricted) of their ad libitum DMI measured during the pre-experimental period. Then, all cows were fed ad libitum for 35 d (period 2). Milk production and DMI were recorded daily. Blood and milk samples were collected once during the pre-experimental period; on d 5, 9, and 27 of period 1; and on d 5, 9, and 30 of period 2. Mammary epithelial cells were purified from milk using an immunomagnetic method to determine the rate of MEC exfoliation. Mammary tissue samples were collected by biopsy at the end of each period to analyze the rates of cell proliferation and apoptosis and the expression of genes involved in synthesizing constituents of milk. Feed restriction decreased milk yield by 3 kg/d but had no effect on rates of proliferation and apoptosis in the mammary tissue or on the expression of genes involved in milk synthesis. The daily MEC exfoliation rate was 65% greater in feed-restricted cows than in control cows. These effects in feed-restricted cows were associated with reduced insulin-like growth factor-1 and cortisol plasma concentrations. When all cows returned to ad libitum feeding, no significant difference on milk yield or MEC exfoliation rate was observed between feed-restricted and control cows, but refeeding increased prolactin release during milking. These results show that the exfoliation process may play a role in regulating the number of MEC in the udders of dairy cows during feed restriction without any carryover effect on their milk production.

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Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

et al. 2020

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Isoflavones are a class of flavonoids present in legumes and are called phytoestrogens because of their estrogen‐like activity. Endogenous estrogen is well known to regulate mammary gland morphogenesis during pregnancy. Each isoflavone also has different physiological activities. However, it is difficult to investigate the direct effect of each isoflavone in mammary morphogenesis in vivo because isoflavones are metabolized into different isoflavones by enteric bacteria. In this study, investigated are the direct influences of coumestrol, daidzein, and genistein on mammary structure development and future milk production ability of mammary epithelial cells (MECs) using in vitro culture models. Mouse MECs are cultured in Matrigel with basic fibroblast growth factor and epidermal growth factor to induce ductal branching and alveolar formation, respectively. Coumestrol and genistein inhibit ductal branching and alveolar formation by affecting the proliferation and migration of MECs with the induction of apoptosis. Daidzein hardly influences mammary structure development. Furthermore, pretreatment with coumestrol adversely affects the induction of milk production ability of MECs. These results suggest that each isoflavone differentially influences mammary morphogenesis and future milk production by affecting MEC behaviors. These results also suggest that the culture models are effective to study mammary epithelial morphogenesis in vitro.

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Regulation of cell number in the mammary gland by controlling the exfoliation process in milk in ruminants

Cited by 45 publications

References 70 publications

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

Milk yield loss in response to feed restriction is associated with mammary epithelial cell exfoliation in dairy cows

Adverse Effects of Coumestrol and Genistein on Mammary Morphogenesis and Future Milk Production Ability of Mammary Epithelial Cells

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