Novel insights into paternal factors influencing the maternal environment and embryo development

Abstract

For many years, reproductive outcomes were considered as being solely determined by the genome of oocytes and sperm. Yet, in the last decades, many other female and male factors have also been found to be relevant. Focusing on the latter, paternal factors have been proposed to be capable of modulating multiple features of the reproductive process, such as sperm physiology, the maternal environment and, even, the offspring health. Considering that the molecular mechanisms underlying this paternal regulation are mostly unknown, the objective of the present Dissertation was to increase the current knowledge on the role played by seminal plasma (SP) and sperm on the reproductive success, using the bovine and porcine as animal models. Chapter 1 investigated the involvement of SP in the modulation of in vivo fertility and the potential pathways behind this regulation. The SP was found to be able to evoke changes in the female reproductive environment, with a positive effect on early embryo development. Next, the protein (particularly AKR1B1) and metabolite composition of SP was examined to address the potential molecular mechanisms able to modulate in vivo fertility. The results indicated that the positive influence of SP on in vivo fertility outcomes could be attributed to the modulation of the female reproductive tract and sperm physiology. On the other hand, Chapter 2 sought to determine to what extent sperm components, including proteins, metabolites and DNA integrity, can shape in vitro fertility outcomes, particularly oocyte fertilization and pre-implantation embryo development. Data showed that the AKR1B1 present in sperm is involved in the regulation of sperm fertilising ability. In addition, sperm metabolism is also able to influence early embryo development. One feasible explanation for such findings is that sperm AKR1B1 levels and metabolism could affect the production of reactive oxygen species, which are known to induce DNA breaks. For this reason, the last study investigated if DNA breaks might influence in vitro fertility outcomes. Interestingly, DNA fragmentation was identified to compromise embryo development, but not sperm fertilizing ability. In conclusion, the findings of this Dissertation supported that seminal factors can directly and indirectly modulate the maternal environment and influence embryo development. Further research should be focused on comprehensively determining the male-female-embryo cross-talk to better understand which factors underlie the reproductive success in mammals