From father to son: the consequences of paternal age on molecular inheritance using the murine model

• Grant number: 24/23080-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2025
• End date: October 31, 2028
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Mayra Elena Ortiz D' Avila Assumpcao
• Grantee: Larissa Araújo Stábile
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/11747-6 - Remote or presential: the importance of communication in the reproductive processes, AP.TEM

Abstract

Aging is a phenomenon that profoundly influences organismal biology, with significant implications for reproductive health. While senescence in female fertility has garnered greater attention, the impact of aging on males and sperm cells is equally critical. With advancing age, sperm structure and functionality are compromised, adversely affecting both the early and later developmental stages of the offspring.This study hypothesizes that senescent male mice (19 and 24 months of age) exhibit an altered transcriptomic profile, encompassing both coding and non-coding RNAs, compared to young males (4 months). This alteration is proposed to result in adverse effects on embryos and offspring. The objective is to delineate the transcriptomic profile of spermatozoa from senescent males using total RNA-seq and miRNA-seq to identify differentially expressed genes (DEGs) and miRNAs. These transcriptomic elements will be correlated with critical biological and metabolic pathways essential for embryonic development, including embryonic genome activation, pluripotency, cell differentiation, cell cycle progression, and cellular stress responses.For validation, gene expression analyses of these transcripts and miRNA targets will be performed in embryos collected at the zygote and 2-cell stages (the time of embryonic genome activation) following the mating of females with young and senescent males. Moreover, the analysis of offspring development and health from birth to adulthood will provide insights into the impact of intergenerational epigenetic inheritance. Understanding these effects may reveal biological pathways and potential targets for future interventions aimed at mitigating the impact of male aging on reproduction and improving offspring health outcomes.