Isoflavones and their metabolites influence the milk production ability of bovine mammary epithelial cells in a type‐specific manner

Abstract

Dairy cows feed on isoflavones as physiologically active substances present in legumes. However, the influences of isoflavones (biochanin A, genistein, formononetin, and daidzein) and their metabolites (p-ethylphenol and equol) on milk components production, tight junctions (TJs), and their regulatory pathways are unclear in bovine mammary epithelial cells (BMECs). In this study, we investigated the influences of isoflavones and their metabolites in BMECs using an in vitro culture model. The influences of isoflavones on milk components production, TJ proteins, and STAT5/STAT3 signaling pathways were different in a type-specific manner.Biochanin A decreased the mRNA expression and secretion of both β-casein and lactoferrin while a decrease in activated STAT5 and an increase in activated STAT3. In contrast, equol increased claudin-3, which is the main components for lesspermeable TJs in lactation, while an increase in activated STAT5. In addition, a mixture of multiple isoflavones based on the intake of red clover increased secretion of lactoferrin, mRNA expression of β-casein, and amount of claudin-3, but a mixture based on soy did not affect the BMECs. Thus, these results indicate that isoflavones in legumes and the metabolic activity of isoflavones in dairy cows when feeding legumes may affect the milk production ability in BMECs.

Causes of Low Milk Supply: The Roles of Estrogens, Progesterone, and Related External Factors

“…Tsugami et al. [ [110] , [111] , [112] , [113] ] and Kumai et al. [ 114 ] have demonstrated using mouse and cow models that isoflavones have different effects on mammary gland development, TJ formation, and expression of milk components, thereby affecting milk production ( Table 2 ).…”

“…[ 114 ] have demonstrated using mouse and cow models that isoflavones have different effects on mammary gland development, TJ formation, and expression of milk components, thereby affecting milk production ( Table 2 ). Specifically, biochanin A and its metabolite genistein have been shown to inhibit mRNA expression and secretion of both β-casein and lactoferrin [ 110 , 112 ]. Biochanin A also reduced activated STAT5 and increased activated STAT3, which are the negative indicators for milk component production and TJ barriers [ 110 ].…”

“…Specifically, biochanin A and its metabolite genistein have been shown to inhibit mRNA expression and secretion of both β-casein and lactoferrin [ 110 , 112 ]. Biochanin A also reduced activated STAT5 and increased activated STAT3, which are the negative indicators for milk component production and TJ barriers [ 110 ]. Genistein can induce apoptosis in MECs and alter the expression of TJ proteins, leading to weakened barrier function [ 113 ].…”

Polyphenols and Lactation: Molecular Evidence to Support the Use of Botanical Galactagogues

“…Similar to daidzein, equol may promote milk production as it activates Stat5 and increases Csn1-3 expression while inactivating Stat3 and decreasing tight junction permeability through claudin-3. [27,122],] Studies of mouse MECs cultured in Matrigel showed that similar to genistein, coumestrol inhibits ductal branching and alveolar formation by inducing apoptosis and reducing the proliferation and migration of MECs. Further studies are required to fully understand the consequences of soy products and isoflavones on milk production and composition.…”

“…Moreover, some polyphenols, such as those found in soy, have estrogenic activity and may positively or negatively affect hormone signaling in the mammary gland, influencing expression, and milk production. [26][27][28] Thus, understanding the molecular mechanisms through which polyphenols affect mammary gland biology will provide a valuable perspective for developing interventions to improve lactation outcomes.…”