M Gentiluomo1, L Crifasi2, A Luddi2, D Locci1, R Barale1, P Piomboni2, D Campa1. 1. Department of Biology, University of Pisa, Via Luca Ghini, 13, Pisa 56126, Italy. 2. Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci 16, Siena 53100, Italy.
Abstract
STUDY QUESTION: Are polymorphisms of taste receptor genes associated with male infertility? SUMMARY ANSWER: This study has showed the associations between three single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male infertility. WHAT IS KNOWN ALREADY: Recent studies showed the expression of taste receptors in the testis and in spermatozoa, suggesting their possible role in infertility. The vast genetic variability in taste genes results in a large degree of diversity in various human phenotypes. STUDY DESIGN, SIZE, DURATION: In this study, we genotyped 19 SNPs in 12 taste related genes in a total of 494 Caucasian male patients undergoing semen evaluation at the Centre of Couple Sterility of the Siena University Hospital. Consecutive patients were enrolled during infertility investigations from October 2014 to February 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Median age of the patients was 36 years (18-58) and 141 were smokers. Genotyping was performed using the allele-specific PCR. The statistical analysis was carried out using generalized linear model (GLM) to explore the association between age, smoking, the genetic polymorphisms and sperm parameters. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that the homozygous carriers of the (G) allele of the TAS2R14-rs3741843 polymorphism showed a decreased sperm progressive motility compared to heterozygotes and (A) homozygotes (P = 0.003). Moreover, the homozygous carriers of the (T) allele of the TAS2R3-rs11763979 SNP showed fewer normal acrosome compared with the heterozygous and the homozygous carriers of the (G) allele (P = 0.002). Multiple comparisons correction was applied and the Bonferroni-corrected critical P-value was = 0.003. LIMITATIONS, REASONS FOR CAUTION: The analysis is restricted to SNPs within genes and to men of Caucasian ancestry. WIDER IMPLICATIONS OF THE FINDINGS: In silico analyses strongly point towards a functional effect of the two SNPs: TAS2R14-rs3741843 regulates TAS2R43 expression, a gene that is involved in cilia motility and therefore could influences sperm mobility; the (T) allele of TAS2R3-rs11763979 increases the expression of the WEE2 antisense RNA one gene (WEE2-AS1). According to Genotype-Tissue Expression (GTEx) project the WEE2 gene is expressed in the testes where presumably it has the role of down regulating meiotic cell division. It is plausible to hypothesize that the WEE2-AS1 increased expression may down regulate WEE2 which in turn can alter the natural timing of sperm maturation increasing the number of abnormal sperm cells. STUDY FUNDING/COMPETING INTEREST(S): None.
STUDY QUESTION: Are polymorphisms of taste receptor genes associated with male infertility? SUMMARY ANSWER: This study has showed the associations between three single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male infertility. WHAT IS KNOWN ALREADY: Recent studies showed the expression of taste receptors in the testis and in spermatozoa, suggesting their possible role in infertility. The vast genetic variability in taste genes results in a large degree of diversity in various human phenotypes. STUDY DESIGN, SIZE, DURATION: In this study, we genotyped 19 SNPs in 12 taste related genes in a total of 494 Caucasian male patients undergoing semen evaluation at the Centre of Couple Sterility of the Siena University Hospital. Consecutive patients were enrolled during infertility investigations from October 2014 to February 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Median age of the patients was 36 years (18-58) and 141 were smokers. Genotyping was performed using the allele-specific PCR. The statistical analysis was carried out using generalized linear model (GLM) to explore the association between age, smoking, the genetic polymorphisms and sperm parameters. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that the homozygous carriers of the (G) allele of the TAS2R14-rs3741843 polymorphism showed a decreased sperm progressive motility compared to heterozygotes and (A) homozygotes (P = 0.003). Moreover, the homozygous carriers of the (T) allele of the TAS2R3-rs11763979 SNP showed fewer normal acrosome compared with the heterozygous and the homozygous carriers of the (G) allele (P = 0.002). Multiple comparisons correction was applied and the Bonferroni-corrected critical P-value was = 0.003. LIMITATIONS, REASONS FOR CAUTION: The analysis is restricted to SNPs within genes and to men of Caucasian ancestry. WIDER IMPLICATIONS OF THE FINDINGS: In silico analyses strongly point towards a functional effect of the two SNPs: TAS2R14-rs3741843 regulates TAS2R43 expression, a gene that is involved in cilia motility and therefore could influences sperm mobility; the (T) allele of TAS2R3-rs11763979 increases the expression of the WEE2 antisense RNA one gene (WEE2-AS1). According to Genotype-Tissue Expression (GTEx) project the WEE2 gene is expressed in the testes where presumably it has the role of down regulating meiotic cell division. It is plausible to hypothesize that the WEE2-AS1 increased expression may down regulate WEE2 which in turn can alter the natural timing of sperm maturation increasing the number of abnormal sperm cells. STUDY FUNDING/COMPETING INTEREST(S): None.
Authors: Antonella Di Pizio; Lukas A W Waterloo; Regine Brox; Stefan Löber; Dorothee Weikert; Maik Behrens; Peter Gmeiner; Masha Y Niv Journal: Cell Mol Life Sci Date: 2019-06-24 Impact factor: 9.261
Authors: Laura Governini; Bianca Semplici; Valentina Pavone; Laura Crifasi; Camilla Marrocco; Vincenzo De Leo; Elisabeth Arlt; Thomas Gudermann; Ingrid Boekhoff; Alice Luddi; Paola Piomboni Journal: J Clin Med Date: 2020-01-18 Impact factor: 4.241