Duangporn Jamsai1, Jennifer Chi Yi Lo2, Robert I McLachlan3, Moira K O'Bryan2. 1. Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: duangporn.jamsai@monash.edu. 2. Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. 3. Monash Institute of Medical Research and Prince Henry's Institute of Medical Research, and Department of Obstetrics and Gynecology, Monash Medical Centre, Clayton, Victoria, Australia; Monash IVF, Richmond, Victoria, Australia.
Abstract
OBJECTIVE: To define RABL2A localization in human sperm and to assess any potential association between RABL2A variants and male infertility associated with oligoasthenospermia. DESIGN: Genetic association study. SETTING: Public university. PATIENT(S): Australian men: 110 oligoasthenospermic infertile and 105 proven fertile. INTERVENTION(S): Human semen samples processed by immunostaining with high-throughput-sequencing platform to screen the entire protein-coding and flanking exon/intron regions of the RABL2A gene. MAIN OUTCOME MEASURE(S): Presence of RABL2A in human sperm and frequencies of RABL2A genetic variants in fertile and infertile men. RESULT(S): RABL2A localization in sperm was highly conserved between mouse and human, being localized to the tail. Direct DNA sequencing revealed 23 RABL2A genetic variants, including 16 intronic, 6 untranslated region (UTR), and one exonic missense variants. Of these, eight variants have not been previously reported. Although the majority of these variants showed no significant association with fertility status, allelic frequency of the intronic variant 114391996 delC was significantly increased in oligoasthenospermic men. Bioinformatics analysis suggested that the 114391996 delC allele would alter the splicing of RABL2A pre-mRNA. CONCLUSION(S): Our data suggest the 114391996 delC allele in the RABL2A gene may act as a risk factor for oligoasthenospermic infertility in Australian men.
OBJECTIVE: To define RABL2A localization in human sperm and to assess any potential association between RABL2A variants and male infertility associated with oligoasthenospermia. DESIGN: Genetic association study. SETTING: Public university. PATIENT(S): Australian men: 110 oligoasthenospermic infertile and 105 proven fertile. INTERVENTION(S): Human semen samples processed by immunostaining with high-throughput-sequencing platform to screen the entire protein-coding and flanking exon/intron regions of the RABL2A gene. MAIN OUTCOME MEASURE(S): Presence of RABL2A in human sperm and frequencies of RABL2A genetic variants in fertile and infertile men. RESULT(S): RABL2A localization in sperm was highly conserved between mouse and human, being localized to the tail. Direct DNA sequencing revealed 23 RABL2A genetic variants, including 16 intronic, 6 untranslated region (UTR), and one exonic missense variants. Of these, eight variants have not been previously reported. Although the majority of these variants showed no significant association with fertility status, allelic frequency of the intronic variant 114391996 delC was significantly increased in oligoasthenospermic men. Bioinformatics analysis suggested that the 114391996 delC allele would alter the splicing of RABL2A pre-mRNA. CONCLUSION(S): Our data suggest the 114391996 delC allele in the RABL2A gene may act as a risk factor for oligoasthenospermic infertility in Australian men.