Effects of dietary folic acid supplementation on lactation performance and mammary epithelial cell development of dairy cows and its regulatory mechanism

Abstract

The experiment investigated the impacts of FA on the proliferation of bovine mammary gland epithelial cells (BMECs) and to investigate the underlying mechanisms. Supplementation of 10 µM FA elevated the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin A2 and cyclin D1, and protein expression of PCNA and Cyclin A1. The mRNA and protein expression of B-cell lymphoma-2 (BCL2) and the BCL2 to BCL2 associated X 4 (BAX4) ratio elevated, while that of BAX, Caspase-3 and Caspase-9 reduced by FA. Both Akt and mTOR signaling pathways were activated by FA. Moreover, the stimulation of BMECs proliferation, the alteration of proliferative genes and protein expression, the change of apoptotic genes and protein expression, and the activation of mTOR signaling pathway caused by FA were obstructed by Akt inhibitor. Suppression of mTOR with Rapamycin reversed the FA-modulated promotion of BMECs proliferation and change of proliferous genes and protein expression, with no impact on mRNA or proteins expression related to apoptosis and FA-activated Akt signaling pathway. Supplementation of rumen-protected FA in cow diets evaluated milk yields and serum insulin-like growth factor-1 and estradiol levels. The results implied that the proliferation of BMECs was stimulated by FA through the Akt-mTOR signaling pathway.

Keywords:

• Folic acid
• bovine mammary epithelial cells
• proliferation
• Akt-mTOR signaling pathway

Author contributions

Jing Zhang: Visualization, writing (original draft), and project administration. Yapeng Liu: Formal analysis and visualization. Lijun Bu: Data curation. Qiang Liu: Conceptualization, funding acquisition, software, supervision, and editing. Caixia Pei: Methodology and validation. Wenjie Huo: Methodology. Chengqiang Xia: Software and validation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by a grant from Natural Science Foundation Project of Science and Technology Department of Shanxi Province [201901D211371] and Key Laboratory for Molecular Animal Nutrition of Ministry of Education in Zhejiang University.