Metformin: A potential therapeutic to correct ovarian dysfunction in the broiler breeder hen
Open Access
- Author:
- Weaver, Evelyn
- Graduate Program:
- Animal Science
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 22, 2023
- Committee Members:
- Francisco Diaz, Major Field Member
Ramesh Ramachandran, Chair & Dissertation Advisor
Wendy Hanna-Rose, Outside Unit & Field Member
Kevin Harvatine, Major Field Member
Adele Turzillo, Program Head/Chair - Keywords:
- Metformin
Broiler breeder hen
Ovary
Metabolism
PCOS - Abstract:
- 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 intensive genetic selection for growth-related traits negatively associated with reproductive function have led to severe ovarian dysfunction in the broiler breeder hen. The hyper-recruitment of prehierarchical follicles and a deranged preovulatory follicular hierarchy often leads to decreased egg production, lower fertility and hatchability of eggs, and decreased viability of embryos. Interestingly, many of the abnormal ovarian and biochemical changes in broiler breeder hens appear to be similar to a condition in women known as polycystic ovary syndrome (PCOS). Metformin, a biguanide compound, is the most commonly prescribed drug for the treatment of polycystic ovary syndrome and is aimed to correct the insulin resistance that is often encountered in women with PCOS. Treatment with metformin has been associated with improved metabolic and reproductive function in women with PCOS, thus, we sought to investigate the effects of metformin on ovarian function in the broiler breeder hen. The main objective of the first study was to determine the effect of metformin on follicular cells isolated from ovarian follicles of the broiler breeder hen. We found that the in vitro treatment of broiler breeder hen granulosa cells isolated from prehierarchical and preovulatory follicles with metformin significantly decreased progesterone secretion. This decrease in steroidogenesis was found to be associated with the inhibition of ERK2 and Akt signaling pathways and a decrease in the expression of genes related to steroid hormone synthesis. These findings suggested that metformin may have the potential to affect the recruitment and maturation of prehierarchical and preovulatory follicles in the broiler breeder hen ovary. The main objective of the second study was to investigate the long term in vivo effect of metformin on ovarian function in the broiler breeder hen. Supplementation of metformin in the diet at 75 mg/kg body weight for 40 weeks enhanced ovarian function through the normalization of the ovarian follicular hierarchy and endocrine profile of reproductive hormones. The improved ovarian function was associated with decreased body weight, decreased abdominal fat pad weight, increased and prolonged egg production and maintenance of fertility and hatchability. Lastly, transcriptomic analysis was conducted in liver tissue from hens in the second study to elucidate the potential mechanism(s) of action that underlie improved metabolic and reproductive function in response to metformin supplementation. The transcriptomic analysis indicated an increase in the abundance of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis, and a decrease in genes related to fatty acid oxidation. These findings suggest that metformin increases and prolongs egg production in broiler breeder hens through the maintenance of yolk-precursor and fatty acid synthesis, previously observed to decline in the gaining hen. Overall, the findings from all three studies suggest that dietary metformin supplementation may be a cost-effective feed additive to improve egg production and the reproductive efficiency of broiler breeder hens.