Postdoctoral Fellow Penn State University University Park, Pennsylvania, United States
Abstract Authors: Evelyn A. Weaver and Ramesh Ramachandran1
1. Center for Reproductive Biology and Health, Department of Animal Science, Pennsylvania State University, University Park, PA
Abstract Text: Broiler breeder hens, the parent stock of commercial broiler chickens, have poor reproductive efficiency due to the selection pressure for superior growth related traits in broiler progeny. Decades of genetic selection for growth-related traits negatively associated with reproductive function have led to severe ovarian dysfunction in the broiler breeder hen. A previous study in our lab found that dietary metformin supplementation resulted in increased and prolonged egg production, however the mechanism(s) of action remain undetermined. The liver plays a significant role in reproduction in the laying hen as it is the main site of de novo lipogenesis and yolk-precursor synthesis and previous studies have shown that the beneficial effects of metformin are mainly through its action in the liver and its ability to improve insulin sensitivity and reduce hepatic glucose production.
Therefore, the main objective of this study was to characterize the transcriptomic profile of liver tissue collected from hens supplemented with metformin in the diet. Broiler breeder hens were supplemented with 0, 25, 50, or 75 mg/kg body weight of metformin mixed in the diet for 40 weeks (n= 45 hens/treatment; 25-65 weeks of age). At the end of the treatment period, liver tissue samples were collected from a subset of hens in each treatment group (n=12 hens/treatment group). Total RNA was extracted from liver tissue and RNA-Seq was used to perform differential gene abundance analysis.
We observed that the hens which received the highest dose of metformin (75 mg/kg body weight) had the largest number of significant differentially abundant genes when compared to the control. The pairwise statistical analysis of transcriptomic data revealed that 1165 genes were differentially abundant (FDR < 0.05) in the liver of hens which received the highest dose of metformin in the diet compared to the hens which received no metformin. Transcriptomic analysis revealed an increase in the abundance of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis. In agreement, Ingenuity Pathway Analysis predicted increased signaling through insulin receptor and estrogen receptor signaling pathways. Furthermore, transcriptomic data were confirmed through quantitative PCR analyses of genes involved in yolk-precursor synthesis and de novo lipogenesis. Based on these findings, we concluded that metformin increases and prolongs egg production in the broiler breeder hen by maintaining yolk-precursor and fatty acid synthesis, previously observed to decline in the aging hen.
