Deciphering the impact of climatic change on sperm epigenome modulation: effects of the sperm source and heat stress on developmental competence of bovine embryos

• Grant number: 24/13164-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Felipe Perecin
• Grantee: Felipe Perecin
• Principal researcher abroad: Luis Miguel Aguila Paredes
• Institution abroad: Universidad de La Frontera (UFRO), Chile
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated researchers: Fabiola Alejandra Zambrano Quezada ; Favián Treulen Seguel ; Flávio Vieira Meirelles ; Juliano Coelho da Silveira ; Lawrence Charles Smith ; Maíra Bianchi Rodrigues Alves ; Ricardo Felmer ; Ricardo Perecin Nociti ; Tiago Henrique Camara De Bem

Abstract

Epididymis is a key tubular organ enclosed to the male gonad (testis) which is morphofunctionally classified in distinct parts, as head, body, and tail, and where occur sperm maturation. In the epididymis tail the sperm are stored and reach functional maturity for fertilization mainly by a mechanism associated with cellular communication via extracellular vesicles (called epididymosomes) released by the epididymal epithelium. Although the specific mechanism that modulates the sperm's fertilizing ability during epididymal transit remains to be elucidated, the sperm epigenome composed of sperm RNAs is modified during the ~10 days that sperm passes through the epididymis. Importantly, the sperm RNA code, in the form of non-coding RNAs (ncRNAs), has been strongly associated with sperm quality and fertilizing potential, as well as critical for proper early embryonic development and transgenerational epigenetic inheritance of paternal traits. Since the male gamete is usually classified as a transcriptionally inert cells because their highly condensed DNA, the sperm RNA code is largely modulated through epididymosomes. Therefore, injuries to the epididymis impact the sperm RNA code and, consequently, the fertilizing ability and embryonic development. By using two different experimental models, we have previously reported a differential profile of microRNAs (miRNAs), a specific subpopulation of ncRNAs, in sperm and epididymal microenvironment (1) after transient scrotal exposure to heat stress, and (2) from low fertility bulls. Furthermore, the different repertoires of RNA and proteins released from the epididymal epithelium, via extracellular vesicles (EVs), display a dynamic profile of ncRNAs able to modify the sperm epigenetic profile and participate in epigenetic inheritance after fertilization. Therefore, pursuing the factors that impact male fertility in the context of environmental stressors (such as global warming) and post-testicular maturation and storage is critical is critical to understanding the paternal contribution to embryonic development and providing new strategies to improve assisted reproductive technologies. Here, this topic will be explored by (1) investigating the impact of epididymal source associated to heat stress on sperm RNA code and developmental features of bovine embryos and (2) providing key sperm-borne molecular factor(s) to the zygotes produced with sperm carrying and altered RNA aiming to rescue and/or modulate the embryonic development. The results of this proposal will shed light on the regulation of the molecular content of sperm and its impact on embryonic development. With these data, we will provide new insights regarding the effects of using sperm from different sources and global warming on male fertility and progeny health. (AU)