ALDH2 Expression, Alcohol Intake and Semen Parameters among East Asian Men.

PURPOSE: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. RESULTS: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). CONCLUSIONS: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

Dopamine D1 and muscarinic acetylcholine receptors in dorsal striatum are required for high speed running.

Dopamine (DA) signaling in the basal ganglia plays important roles in motor control. Motor deficiencies were previously reported in dopamine receptor D1 (D1R) and D2 (D2R) knockout mice. While these results indicate the involvement of DA receptors in motor execution, the null knockout (KO) mouse lacks the specificity necessary to determine when and where in the brain D1R and D2R function in motor execution. To address these questions, we restricted the loss of function temporally and spatially by using D1R conditional knockdown (cKD) mice and mice injected with antagonists against DA receptors directly into the dorsal striatum. In addition, we address the DA and acetylcholine (ACh) balance hypothesis by using antagonists against ACh receptors. We tested the motor ability of the mice with a newly devised task named the accelerating step-wheel. In this task, the maximum running speed was measured in a situation where the wheel rotation speed was gradually accelerated in one trial. We found significant decreases in the maximum running speed of D1R cKD mice and the mice injected with the antagonist against D1R or muscarinic ACh receptor. These results indicated that D1R and muscarinic ACh receptor in the dorsal striatum play pivotal roles in the execution of walking/running.