Contributions of spermatozoa to embryogenesis: assays to evaluate their genetic and epigenetic fitness

During fertilization, spermatozoa contribute genetic and epigenetic factors that affect early embryogenesis. Genetic factors include a haploid genome with intact coding regions and regulatory regions for essential genes. The DNA must contain the proper copy number of essential genes, and cannot have increased single- or double- stranded DNA breaks. Epigenetic factors include a functional centrosome, proper packaging of the chromatin with protamines, modifications of histones, and imprinting of genes. Additionally, the fertilizing spermatozoon provides mRNAs and micro RNAs, which may contribute to the embryonic transcriptome and regulate embryonic gene expression. These epigenetic factors, directly or indirectly, affect the expression of genes in the developing embryo. Each of these contributions represents areas of potential sperm dysfunction, and they are the focus of ongoing research to develop assays which will allow further analysis of their clinical significance. This review briefly describes the current status of research into the genetic and epigenetic contributions of spermatozoa to embryogenesis, and the quest for clinical screening assays. The challenges to validation and clinical application of such testing are also discussed.