p53 and mitogen-activated protein kinase pathway protein profiles in fresh and frozen spermatozoa

Abstract

Sperm or testicular tissue cryopreservation is performed in cases of male infertility as a treatment for the preservation of fertility. When these sperm cells are used in assisted reproductive techniques, fertilisation rates, developmental and implantation potential of embryos decrease and the abortion rates increase. In the present work, differences of both phosphorylation and expression levels of p53 and Mitogen-activated protein kinases (MAPK) proteins were analysed in 61 individual sperm samples before and after cryopreservation. We observed that p53 protein residue at Ser 15 was phosphorylated after cryopreservation. Because MAPK pathway activations may be involved in p53 phosphorylation, MAPK/ERK, Stress-activated protein kinases (SAPK)/JNK and p38MAPK proteins were also investigated. Analysis showed that p38MAPK phosphorylations increased significantly. However, ERK and JNK expressions and phosphorylations decreased, although the differences were not statistically significant. According to our results, it may be suggested that cryopreservation process activates p53 via p38 MAPK pathway that subsequently causes apoptosis, which may be related to sperm parameters.

Profiling signaling proteins in human spermatozoa: biomarker identification for sperm quality evaluation

“…This promotes p53 uncoupling from MDM2, leading to p53 activation and consequently cell death promotion. In spermatozoa, p38 seems to be the main kinase responsible for p53 phosphorylation at S15 (76). Since p38 phosphorylation also correlates negatively with motility (both in this study and in the literature) (44,70), we suggest that a single signaling pathway controlled by sequential phosphorylation could be involved in spermatozoa motility.…”

“…In spermatozoa, p53 is coupled with MDM2 in physiologic conditions. Upon DNA damage, p53 undergoes phosphorylation at S15 (primary target) (76). This promotes p53 uncoupling from MDM2, leading to p53 activation and consequently cell death promotion.…”

The role of miR‐128‐3p through MAPK14 activation in the apoptosis of GC2 spermatocyte cell line following heat stress

“…We then detected an increase in the p‐MAPK14 level after testicular hyperthermia in mice, indicating that the MAPK14 pathway was activated after testicular heat treatment. Some studies suggest that MAPK14 activation may be associated with poor sperm quality that impairs fertility 32,33 …”

Soluble Fibrinogen‐like protein 2 plays a role in varicocele induced male infertility

“…Upon these receptor activations; sFGL‐2 initiate activation of mitogen‐activated protein kinase and nuclear NF‐κβ in high concentration and in addition it acts as transforming growth factor beta factor in low concentration (Wang et al., 2014). These pathways are important in spermatozoa apoptosis (Karabulut, Demiroğlu‐Zergeroğlu, Yılmaz, Sağır, & Delikara, 2014; Wang & Su, 2018) and capacitation (Luna et al., 2017) and immune‐tolerance (Pierucci‐Alves, Midura‐Kiela, Fleming, Schultz, & Kiela, 2018).…”