The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We production), NF-k kB activation, and apoptosis, and also mitigated rac1-regulated H 2 O 2 production and NF-k kB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Our previous work identified NHA1, a testis-specific sodium–hydrogen exchanger, is specifically localized on the principal piece of mouse sperm flagellum. Our subsequent study suggested that the number of newborns and fertility rate of NHA1-vaccinated female mice are significantly stepped down. In order to define the physiological function of NHA1 in spermatozoa, we generated Nha1Fx/Fx, Zp3-Cre (hereafter called Nha1 cKO) mice and found that Nha1 cKO males were viable and subfertile with reduced sperm motility. Notably, cyclic AMP (cAMP) synthesis by soluble adenylyl cyclase (sAC) was attenuated in Nha1 cKO spermatozoa and cAMP analogs restored sperm motility. Similar to Nha1 cKO males, Nha2Fx/Fx, Zp3-Cre (hereafter called Nha2 cKO) male mice were subfertile, indicating these two Nha genes may be functionally redundant. Furthermore, we demonstrated that male mice lacking Nha1 and Nha2 genes (hereafter called Nha1/2 dKO mice) were completely infertile, with severely diminished sperm motility owing to attenuated sAC-cAMP signaling. Importantly, principal piece distribution of NHA1 in spermatozoa are phylogenetically conserved in spermatogenesis. Collectively, our data revealed that NHA1 and NHA2 function as a key sodium–hydrogen exchanger responsible for sperm motility after leaving the cauda epididymidis.

A downward secular trend in the onset of puberty was clearly shown in the population. The age at childhood onset of growth did not correlate with the timing of puberty (r = -0.01 and 0.05, p > 0.7 and 0.1 in boys and girls, respectively). Normal ranges of the age at childhood onset of growth are in need of revise, as this study indicates. The new reference presented here could be a reliable indicator in further studies.