Paternal factors and embryonic development: Role in recurrent pregnancy loss

Abstract

The events occurring at the maternal–foetal interface define a successful pregnancy but the current paradigm has shifted towards assessing the contribution of spermatozoa for embryogenesis. Spermatozoa with defective DNA integrity may fertilise the oocyte but affect subsequent embryonic development. The present case–control study was conducted in male partners of couples experiencing recurrent pregnancy loss (RPL) to assess the gene expression of spermatozoal FOXG1, SOX3, OGG1, PARP1, RPS6, RBM9, RPS17 and RPL29. This was correlated with reactive oxygen species (ROS) levels and DNA Fragmentation Index (DFI). Semen samples were obtained from 60 cases and 30 fertile controls. Gene expression was done by qPCR analysis, and relative quantification was calculated by the 2−ΔΔCt method. Chemiluminescence and the sperm chromatin structure assay were used to measure the ROS and DFI levels respectively. FOXG1, OGG1, RPS6 and RBM9 were seen to be upregulated, while SOX3 and PARP1 were downregulated. Relative expression of SOX3, OGG1, RPS6 and RPS17 showed a significant difference between patients and controls (p < 0.05). RPL patients were seen to have high ROS (>27.8; p = 0.001) and DFI (>30.7; p < 0.0001) with respect to controls. Sperm transcript dysregulation and oxidative DNA damage can be “carried over” after implantation, thus affecting embryogenesis and health of the future progeny.

The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword

“…Whether similar mechanisms underpin the observed association between oxidative stress in the male germ line and developmental abnormalities in human embryos that culminate in repeated early miscarriage [59,115] is currently an open question that has not yet been addressed. It is known that ROS generation and DNA fragmentation are significantly elevated in the spermatozoa of female partners experiencing recurrent early pregnancy loss [116] however the importance of 4HNE adduction of sperm centriolar proteins in the aetiology of this condition is unknown.…”

Impact of Paternal Genome with a High DNA Fragmentation Index (>60%) on Early Embryonic Development

“…Also, we can assume that a patient with a sperm sample revealing degraded DNA can give live births. Only there is a risk of transmission of altered genetic material to the offspring, which may be responsible for the subsequent development of genetic diseases or even be responsible for the appearance of childhood cancers, as reported by several studies [51][52][53].…”

The Efficacy of Hyaluronic Acid Binding (HAB) in the Treatment of Male Infertility: A Systematic Review of the Literature

“…Therefore, this technique presents a valid option for the treatment of patient groups commonly excluded from RCTs. For example, a recent study and two meta-analyses have reported that male partners of couples experiencing recurrent pregnancy loss (RPL) demonstrate significantly higher sperm ROS concentrations and altered gene expression profiles [77], and increased levels of sperm DNA fragmentation [78,79], suggesting that high frequencies of DNA damage may be beyond the repair capabilities of the oocyte, and consequent chromosomal anomalies may be incompatible with post-implantation development and viability. Such patients are increasingly referred for assisted conception techniques despite an ability to naturally achieve pregnancy, while being underrepresented in embryological research [80].…”