Sistema ETD

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Tesi etd-03172017-102629

Tipo di tesi
Tesi di laurea magistrale
Association between polymorphisms in taste receptor genes and male infertility
Corso di studi
relatore Campa, Daniele
correlatore Prof. Barale, Roberto
correlatore Prof. Dal Monte, Massimo
Parole chiave
  • infertility
  • SNP
  • male infertility
  • taste receptors
  • gene
Data inizio appello
Data di rilascio
Riassunto analitico

Infertility affects 15% of the European population and is clinically defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. A male contribution to infertility is found in 45-50% of the cases. In 30-45%, the cause of the abnormal semen parameters is not identified (idiopathic male infertility).
Among the known modifiable lifestyle risk factors for male infertility there are: age when starting a family (paternal age), nutrition, weight management, exercise, psychological stress, cigarette smoking, recreational and prescription drugs use, alcohol consumption, environmental and occupational exposures.
Male infertility has also several genetic risk factors among which: Y chromosome-linked copy number variation (CNV), Y chromosome micro deletion and low penentrance mutations such as single nucleotide polymorphism (SNP). However a very small number of risk loci have been identified so far especially in Caucasians.
Among possible gene candidates taste receptor make attractive candidates since they are expressed in the testis and in spermatozoa
and their potential role as chemo-receptors. In addition in a recent study reported that the lack of expression of TAS1R3 and GNAT3 leads to infertility and abnormal testicular development. Finally it is well known that polymorphic variants in taste genes are often functional and may exert a profound effect on the protein phenotype. The aim of this study was to test whether genetic variability in taste receptor could be associated to male infertility.
This study was conducted in a total of 492 Caucasian males patients undergoing semen evaluation at the Centre of Couple Sterility of the Siena University Hospital. All the patients were enrolled during infertility diagnosis from October 2014 to February 2016. For all subjects information on age and smoking habits was collected. We have selected 19 SNPs in 12 taste related genes that have been reported to be expressed in human and or mice testis or sperm cells. We used a generalized linear model (GLM) to explore the association between age, smoking, the genetic polymorphisms and the sperm parameters. Smoking was assessed as a dichotomous variable (yes/no) while age as a continuous variable. When testing the association between the SNPs and the sperm parameters we used a dominant, co-dominant and recessive inheritance model and we adjusted for age. We observed that two polymorphisms showed a statistically significant association with the sperm parameters, considering a Bonferroni corrected threshold of significance of P=0.003. In particular, the homozygous carriers of the minor (G) allele of the TAS2R14-rs3741843 polymorphism showed a decreased sperm progressive motility (mean progressive motility 0.35) compared to heterozygous and common (A) homozygous (mean progressive motility 0.46) (P=0.002). Moreover, the homozygous carriers of the minor (T) allele of the TAS2R3-rs11763979 SNP showed a decreased number of normal acrosome (mean value= 0.085) compared with the heterozygous (mean value= 0.096) and the homozygous carriers of the major (G) allele (mean value= 0.114) (P=0.003). TAS2R14-rs3741843 and TAS2R3-rs11763979 show a plethora of eQTL in various tissues and they regulate with a convincing statistical significance several genes. These results are potentially relevant and further our understanding on the genetic of idiopathic male infertility.