Contribution of semen to early embryo development: fertilization and beyond

Abstract

BACKGROUND It has long been thought that the factors affecting embryo and foetal development were exclusively maternally derived; hence, if issues regarding fertility and embryo development were to arise, the blame has traditionally been placed solely on the mother. An escalating interest in how paternal factors influence embryo development, however, has begun to prove otherwise. Evidence suggests that both seminal plasma (SP) and sperm contribute multiple factors that shape embryogenesis. This review thus focuses on the role that semen has in driving early embryonic development, and describes how paternal factors, such as SP, sperm centriole, sperm proteins, sperm RNA, sperm DNA, and its integrity, together with epigenetics, may influence the female reproductive tract and post-fertilization events. The important contributions of paternal factors to embryo development highlight the imperative need for further research in this area, which is sure to bring forth breakthroughs leading to improvements in infertility diagnosis and ART as well as reducing the risk of miscarriage. OBJECTIVE AND RATIONALE This review provides a comprehensive overview of the role of human semen in development of the early embryo, with the aim of providing a better understanding of the influence of SP and sperm on early embryonic divisions, gene and protein expression, miscarriage, and congenital diseases. SEARCH METHODS PubMed searches were performed using the terms ‘sperm structure’, ‘capacitation’, ‘acrosome reaction’, ‘fertilization’, ‘oocyte activation’, ‘PLCζ’, ‘PAWP’, ‘sperm-borne oocyte activation factor’, ‘oocyte activation deficiency’, ‘sperm centriole’, ‘sperm transport’, ‘sperm mitochondria’, ‘seminal plasma’, ‘sperm epigenetics’, ‘sperm histone modifications’, ‘sperm DNA methylation’, ‘sperm-derived transcripts’, ‘sperm-derived proteins’, ‘sperm DNA fragmentation’, ‘sperm mRNA’, ‘sperm miRNAs’, ‘sperm piRNAs’, and ‘sperm-derived aneuploidy’. The reviewed articles were restricted to those published in English between 1980 and 2022. OUTCOMES The data suggest that male-derived factors contribute much more than just the male haploid genome to the early embryo. Evidence indicates that semen contributes multiple factors that help shape the fate of embryogenesis. These male-derived factors include contributions from SP, the paternal centriole, RNA and proteins, and DNA integrity. In addition, epigenetic changes have an impact on the female reproductive tract, fertilization, and early stages of embryo development. For example, recent proteomic and transcriptomic studies have identified several sperm-borne markers that play important roles in oocyte fertilization and embryogenesis. WIDER IMPLICATIONS This review highlights that several male-derived factors are required to work in tandem with female counterparts to allow for correct fertilization and development of the early embryo. A deeper understanding of the contributions of paternal factors that are shuttled over from the sperm cell to the embryo can shed light on how to improve ART from an andrological perspective. Further studies may aid in preventing the passing on of genetic and epigenetic abnormalities of paternal origin, thus decreasing the incidence of male factor infertility. In addition, understanding the exact mechanisms of paternal contribution may assist reproductive scientists and IVF clinicians in determining new causes of recurrent early miscarriage or fertilization failure.

Contribution of the epididymis beyond fertilization: relevance of CRISP1 and CRISP3 for sperm DNA integrity and early embryo development

“…Previous observations from our laboratory showed that females mated with males with mutations in Crisp1 and Crisp3 genes (C1/C3 DKO) exhibited normal in vivo fertilization rates but significantly lower percentages of embryo development, supporting the notion that male-derived factors are required to allow for correct development of the embryo (Vallet-Buisan et al ., 2023). Moreover, we observed that triple knockouts lacking CRISP1, CRISP2 and CRISP3 as well quadruple knockouts lacking the four members of the family exhibited both fertilization and embryo development defects, supporting the lack of CRISP1 and CRISP3 as relevant for the embryo development phenotype.…”

“…Considering various reports showing that male accessory glands contribute to proper embryo development without affecting fertilization rates (Jodar, 2019; Ma et al ., 2022; Vallet-Buisan et al ., 2023; W. S. et al .,1988), the possibility existed that the sperm defects leading to the embryo development phenotype were associated with the lack of CRISP1 and CRISP3 in the accessory gland secretions.…”

Sperm DNA fragmentation index: Limited effectiveness on predicting embryo quality in assisted reproduction technology treatments

“…Nonetheless, accumulating evidence suggests that contributions from male-derived factors extend well beyond the provision of the male haploid genome to the early embryo, and semen may play a pivotal role in the intricacies of embryogenesis. 30 In conclusion, despite the potential diminishment of the predictive signi cance of sperm parameters on embryo quality due to the application of semen optimization processes, our data still indicated that sperm DFI could exhibit some predictive power for the fertilization rate during ART cycles. Furthermore, a threshold value of 21.15% has been identi ed, offering potential predictive utility for high fertilization rates (≥ 80%).…”

Application of Flow Cytometry Using Advanced Chromatin Analyses for Assessing Changes in Sperm Structure and DNA Integrity in a Porcine Model

“…In this regard, sperm DNA fragmentation (SDF) is used most in human clinics and breeding centers [7,8]. However, SDF is only one of many levels in sperm chromatin evaluation, and solely focusing on it ignores the complex structural, epigenetic, and other molecular features affecting sperm fertility, embryo development, and even the health and well-being of the offspring [9,10].…”