Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health

Hypertensive vasculopathy

Essential hypertension is characterized by an increase in total peripheral vascular resistance, due primarily to a decrease in lumen diameter and an increase in media thickness. Underlying these phenomena are altered vascular tone (decreased relaxation and/or increased contraction) and structural remodeling. Endothelial dysfunction and arterial remodeling characterize the vascular phenotype of hypertension, known as “hypertensive vasculopathy.” Initial factors contributing to vasculopathy of hypertension involve increased transmural pressure, changes in blood flow, impaired endothelial function, and altered vascular smooth muscle cell (VSMC) contractility. More chronic changes are associated with perturbed VSMC growth, migration, differentiation, calcification and inflammation, and production of extracellular matrix proteins, responsible for structural remodeling. At the level of the vascular cells, receptors are activated by vasoactive agents and mechanical forces triggering intracellular signaling pathways and generation of reactive oxygen species (ROS). These subcellular events underlie VSMC dedifferentiation, realignment, calcification, and growth and stimulate inflammation, fibrosis, and osteogenic transformation, which contribute to endothelial dysfunction and thickening of the vascular wall. Such changes play a major role in the vasculopathy of hypertension