The ACE deletion/deletion genotype was identified in 90 men, including 9.8% of healthy fertile men, 10.3%, 32.70% and 35.2% of those with asthenozoospermia, asthenoteratozoospermia and oligoasthenoteratozoospermia, respectively.
As F-actin is required for maintaining structural integrity and hyperactivated motility in sperm, our finding has significant implications in light of our previous reports of reduced GRP78 phosphorylation and the actin-based motility pathway being significantly altered in asthenozoospermia.
ADCY10 is a susceptibility gene for dominant absorptive hypercalciuria (OMIM#143870); however, no ADCY10 variations have been confirmed to cause human asthenozoospermia to date.
We report here for the first time that an abnormal AA metabolic network could reduce sperm motility via P38 MAPK activation through the LOX, cytochrome P450 and COX metabolic pathways, which might be an underlying pathomechanism of asthenozoospermia.
We report here for the first time that an abnormal AA metabolic network could reduce sperm motility via P38 MAPK activation through the LOX, cytochrome P450 and COX metabolic pathways, which might be an underlying pathomechanism of asthenozoospermia.
Overall, this work identifies a novel genetic cause of asthenozoospermia due to MMAF and suggests that in humans, more deleterious mutations of AK7 might induce PCD.
AKAP4, a protein regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized with one another in the sperm tail, which might contribute to reduced sperm motility.
JAM-A, like PMCA4, plays a role in Ca2+ regulation, since deletion of Jam-A results in significantly elevated intracellular Ca2+ levels and reduced sperm motility.
The data support a quaternary complex model in which PMCA4 co-ordinates Ca<sup>2+</sup> and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4<sup>-/-</sup> males.
Our results revealed no significant difference in frequencies of genetic variants in PMCA4 gene between men with normal and those with reduced sperm motility.