Daniel R. GreenbergBhambhvani, Hriday P.Hriday P.BhambhvaniBasran, Satvir S.Satvir S.BasranSalazar, Brett P.Brett P.SalazarRios, Luis CarlLuis CarlRiosSIN-JIN LIChen, Che-HonChe-HonChenMochly-Rosen, DariaDariaMochly-RosenEisenberg, Michael L.Michael L.Eisenberg2025-02-082025-02-082022-03-280022-53471527-3792https://www.scopus.com/record/display.uri?eid=2-s2.0-85134311509&origin=recordpagehttps://scholars.lib.ntu.edu.tw/handle/123456789/725225Purpose: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.enalcohol drinkingALDH2 proteinhumaninfertilitymalejournal article10.1097/ju.0000000000002682