Biological Aging and Uterine Fibrosis in Cattle: Reproductive Trade-Offs from Enhanced Productivity.

Reproductive efficiency in cattle remains sub-optimal, with pregnancy rates often below 50%, despite fertilization rates approaching 100%, indicating that implantation failure and/or early embryonic loss are major limiting factors. This disparity highlights the need to understand the biological and physiological mechanisms underlying implantation failure. This review elucidates the cellular and molecular mechanisms underlying reduced pregnancy rates, with a particular focus on biological aging and fibrosis in the reproductive organs as emerging contributors to uterine dysfunction. Accumulated evidence suggests that metabolic demands associated with intensive breeding strategies aimed at maximizing meat and milk productivity may induce multiple forms of stress, including oxidative stress, metabolic stress, and inflammation, which accelerate biological aging and fibrosis in the female reproductive tract. However, the direct molecular mechanisms remain poorly characterized. We hypothesize that biological aging and fibrosis are interconnected mechanisms contributing to impaired uterine function, resulting in reduced implantation rates. By summarizing recent findings and adopting a comparative perspective, this review explores the extent to which insights from human and mouse models can be applied to cattle, considering species-specific reproductive physiology and metabolic adaptations. It explores their relevance to reproductive inefficiencies and discusses potential strategies to enhance fertility and extend bovine reproductive longevity.