We analysed the ECM-related gene expression pattern in the two groups. In particular, we characterized and quantified the major ECM components, namely collagen, elastin, glycosaminoglycans, fibronectin and laminins, in young and aged ovaries. In the present study, we adopted the porcine as a model, based on its anatomical and physiological similarities with the human and we analyzed the impact of aging on ovarian ECM. However, at present, only scattered information is available in the literature regarding aging mechanobiology of the reproductive tissues, where several aspects still need to be elucidated. In this contest, follicles and oocyte developmental quality have been demonstrated to be strongly influenced by biochemical cues as well as by the physical ovarian microenvironment. Reproductive biology addressed growing interest in ovarian mechanobiology in the last decade and, in particular, the dynamic reciprocity that exists between ovarian cells and their microenvironment is currently under investigation. In addition, recent studies also suggested that aging may induce critical alterations in ECM composition and organization, resulting in biomechanical and biochemical ECM property modifications, that impact cell-to-matrix interactions as well as cell fate and behaviour. However, cell ability to sense changes in ECM compliance (mechanosensation) and to transduce these stimuli into biochemical signals (mechanotransduction) are negatively affected by aging progression. Cells are indeed able to respond to physical and mechanical cues exerted by the surrounding environment modifying their own morphology, polarity, adhesion, migration, growth, gene expression, and functions. Indeed, during the last years, it has been clearly demonstrated that ECM contributes not only to physical scaffolding and structural support but also provides biochemical and biomechanical stimuli directly influencing cell behaviour. Recent studies also suggest that the non-cellular compartment of the tissues, the extracellular matrix (ECM), may play a key role in aging progression. Īging is generally described as a complex, multifaceted process, characterized by a progressive accumulation of macroscopic and microscopic modifications, accompanied by molecular and cellular damages that can affect organs, tissues, cells, and subcellular organelles, causing severe biological degenerations and a gradual loss of organ functions. Reproductive aging has therefore gradually become a key health issue and an adequate understanding of its mechanisms is essential in order to prevent age-related diseases and to promote health and longevity in women. Although medical care advances and rising living standards have contributed to increasing lifespan, the age of menopause has remained constant at the age of ~50 years, leading women to live longer in suboptimal endocrine conditions. This leads to multiple medical and psychosocial problems, such as osteoporosis, cardiovascular disease, autoimmune disorders, and depression. In mammals, the female reproductive system is the first to show signs of physiological aging, with fertility decline and hormonal dysfunctions that can, in turn, affect overall health. Furthermore, in order to study the mechanisms driving aging and identify possible strategies to counteract ovarian tissue degeneration, we here described the successful production of a 3D ECM-based biological scaffold that preserves the structural modifications taking place in vivo and that represents a powerful high predictive in vitro model for reproductive aging and its prevention. This is accompanied by a dynamic response in gene expression levels of the main ECM- and protease-related genes, indicating a direct impact of aging on the transcription machinery. We here analyze the impact of aging on the ovarian extracellular matrix (ECM), and we demonstrate significant changes in its composition and organization with collagen, glycosaminoglycans, and laminins significantly incremented, and elastin, as well as fibronectin, decreased. An adequate understanding of ovarian senescence mechanisms is essential to prevent age-related diseases and to promote wellbeing, health, and longevity in women. Among these, reproductive aging is gradually becoming a key health issue because the age of menopause has remained constant at ~50 years, leading women to live longer in suboptimal endocrine conditions. Although this reflects positive human development, it also poses new challenges. Advances in medical care, improvements in sanitation, and rising living standards contribute to increased life expectancy.
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