Yes-associated protein 1 is essential for maintaining lactation via regulating mammary epithelial cell dynamics and secretion capacity

Understanding the physiology and molecular mechanisms of lactogenesis is crucial for enhancing mammalian milk production. Yes-associated protein 1 (YAP1) regulated mammary epithelial cell survival during pregnancy, but its role in lactation maintenance remains unclear. We found that YAP1 was highly expressed in mammary gland across specie, with elevated expression levels during murine gestation and lactation, particularly localized in alveoli epithelial cells. In vivo administration of a YAP1 inhibitor impaired murine milk yield, mammary gland weight, alveolar structure, and mammary epithelial cell dynamics. In vitro, YAP1 positively affected mammary epithelial cell growth and the synthesis of triglyceride and α-casein. Notably, the primary lactogenesis hormone Prolactin induced cell growth and triglyceride secretion while enhancing YAP1 expression and activity. In contrast, Melatonin inhibited cell growth and triglyceride synthesis, decreasing YAP1 expression and activity. YAP1 knockdown compromised prolactin induced effects, whereas YAP1 overexpression partially rescued cell functions inhibited by melatonin. Finally, Bioinformatics analyses revealed that YAP1 regulated multiple biological processes related to lactogenesis, including cell cycle, apoptosis, endoplasmic reticulum, amino acid transport and biosynthesis, etc. These finding indicated that YAP1 is essential for mammary epithelial cells growth and secretion and played an essential role in the lactating endocrine network by mediating key hormone functions.