De Pai para Filho - Gerir a Obesidade Infantil Paterna com Intervenções para Perda de Peso e Efeitos Transgeracionais

Our research proposal aims to explore the enduring impacts of childhood obesity (CO) during adulthood and its potential implications on the health of future generations. A critical aspect of our investigation is centered around understanding the optimal approach to weight loss post-CO—whether through exercise, dietary modifications, or a combination of both. Currently, this remains an unanswered question with significant clinical and societal implications. The primary focus of our study is to unravel metabolic and epigenetic signatures influenced by CO and to decipher the intricate effects of weight loss induced by various interventions. These signatures hold pivotal importance as they can potentially serve as diagnostic tools for assessing sperm quality in the context of reproductive technologies. Furthermore, the insights derived from our research will contribute to advising on the opportune window for conception, a crucial aspect of reproductive health. Our specific aims outline a systematic approach to address various facets of this complex issue: Investigate Sperm Physiology Regulation: We aim to focus on how CO and subsequent weight loss interventions (by dietary correction, exercise or a combination of both) regulate sperm physiology; Identify Epigenetic Biomarkers: Our research will seek to identify epigenetic biomarkers present in sperm that are responsive to CO and weight loss; Assess Impact on Offspring Health: We plan to assess the impacts of CO and different weight loss approaches on the metabolic and fertility health of the offspring; Reveal Mechanisms mediating the Effects: The study will endeavor to reveal the epigenetic and metabolic mechanisms orchestrating these effects and how they respond to weight loss induced by diet, exercise, or a combination of both; Integrate Multi-Omics Approaches: We will integrate results obtained from metabolomics, proteomics, and epigenomics studies to provide a comprehensive understanding; Validate Biomarkers in Human Sperm: The identified biomarkers will be validated in sperm samples from men, ensuring the relevance and applicability of our findings; Evaluate Paternal Reproductive Health: Contribute to the evaluation of potential paternal reproductive health at the moment of conception in relation to CO and weight loss; Examine Father Metabolism and Epigenetic Transmission: Investigate the effects of father metabolism (CO and weight loss) and the epigenetic information transmitted by sperm to the offspring. Create a platform for single-spermatozoon RNA profile analysis: Using a microgel based technology we plan to develop a single-spermatozoon RNA profile analysis that can be optimized to personalized male fertility management during assisted reproduction and family plan. Our holistic approach, as depicted in the attached Figure (Annex I), is designed to shed light on the intricate interplay between CO, different weight loss strategies, and their profound effects on reproductive health. The ultimate goal is to provide valuable insights for clinical practice and enhance societal awareness regarding the long-term consequences of CO and the potential benefits of weight loss interventions.