Weaver Evelyn Anne, Connolly Nathan Patrick, Kim Tae Hyun, Ramachandran Ramesh
Center for Reproductive Biology and Health, Department of Animal Science, The Pennsylvania State University, University Park, PA, USA.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
Biol Reprod. 2025 Jul 13;113(1):169-181. doi: 10.1093/biolre/ioaf072.
The liver is critical in avian reproduction as it is the primary site of de novo lipogenesis and yolk precursor synthesis. Broiler breeder hens, the parents of commercial broiler chickens, have poor reproductive efficiency due to declining egg production from 45 weeks of age. We found that metformin increases fertile egg production in the aging broiler breeder hen, which was correlated with reduced body weight, reduced fat pad weight, and altered reproductive hormone profiles. This study aimed to characterize the liver transcriptome of the same broiler breeder hens supplemented with metformin in the diet at 0 or 75 mg/kg body weight for 40 weeks (25-65 weeks of age; n = 45 hens/treatment). Liver tissue was collected from a subset of hens (n = 12 hens/treatment group) at 65 weeks of age, and RNA was extracted and sequenced using next-generation sequencing. Differential gene abundance analysis revealed that metformin treatment led to significant changes in gene expression. Further transcriptomic analysis highlighted increased expression of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis. Quantitative PCR analysis revealed increased expression of ESR1, APOB, APOV1, VTG2, ADIPOQ, ADIPOR2, and ACACA mRNA and decreased expression of PCK1 mRNA while plasma triglyceride and non-esterified fatty acid levels were lower in metformin-treated animals compared to controls. The present study suggests that metformin supplementation supports prolonged egg production in aging broiler breeder hens by sustaining yolk precursor and fatty acid synthesis that are typically diminished in aging broiler breeder hens.
肝脏在禽类繁殖中至关重要，因为它是从头脂肪生成和卵黄前体合成的主要部位。肉种鸡是商品肉鸡的亲本，由于45周龄后产蛋量下降，其繁殖效率较低。我们发现二甲双胍可提高老龄肉种鸡的受精蛋产量，这与体重减轻、脂肪垫重量减轻以及生殖激素谱改变有关。本研究旨在描述同一批肉种鸡在0或75 mg/kg体重的日粮中添加二甲双胍40周（25至65周龄；每组n = 45只母鸡）后的肝脏转录组特征。在65周龄时从一部分母鸡（每组n = 12只母鸡）收集肝脏组织，提取RNA并使用下一代测序技术进行测序。差异基因丰度分析表明，二甲双胍处理导致基因表达发生显著变化。进一步的转录组分析突出显示了与雌激素刺激的卵黄前体合成、胰岛素刺激的从头脂肪生成以及AMPK介导的葡萄糖稳态相关的基因表达增加。定量PCR分析显示，与对照组相比，二甲双胍处理组动物的ESR1、APOB、APOV1、VTG2、ADIPOQ、ADIPOR2和ACACA mRNA表达增加，PCK1 mRNA表达降低，同时血浆甘油三酯和非酯化脂肪酸水平较低。本研究表明，补充二甲双胍可通过维持老龄肉种鸡中通常会减少的卵黄前体和脂肪酸合成，来支持老龄肉种鸡延长产蛋期。
