title: The association of aromatase (CYP19) gene variants with sperm concentration and motility.
abstract: The irreversible transformation of androgens into oestrogens is catalysed by cytochrome P450 aromatase. In the present study, we explored the contribution of the (TTTA)(n) polymorphism in the aromatase gene (CYP19) to sperm concentration and motility. Ninety normozoospermic and 60 oligospermic men were examined during infertility examinations. DNA was extracted from spermatozoa, and the CYP19 (TTTA)(n) polymorphism was genotyped by PCR. Genotype analysis revealed six CYP19 (TTTA)(n) alleles with 7-12 repeats. The allelic distribution of the CYP19 (TTTA)(n) polymorphism differed between normozoospermic and oligospermic men (P<0.01). Oligospermic men less frequently had long CYP19 alleles than did normozoospermic men (25 and 37.8%, respectively; P<0.02). The higher frequency of short CYP19 alleles in oligospermic men compared to normozoospermic men (43.3 and 28.3%, respectively; P<0.01) was primarily due to the distribution of the CYP19 (TTTA)(7) allele. The CYP19 (TTTA)(7) allele was associated with lower sperm concentration in normozoospermic men (P<0.01) and in the total study population (P<0.01); it was also associated with lower sperm motility in normozoospermic men (P<0.05) and in the total study population (P<0.01). In conclusion, the CYP19 (TTTA)(7) allele probably impairs aromatase activity, which in turn alters aromatase and oestrogen levels in the testis, leading to decreased sperm concentration and motility. These findings support the significance of cytochrome P450 aromatase in human spermatogenesis and consequently in semen quality.
authors.affiliation: Genetics and IVF Unit, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina 45110, Greece.
authors.forename: Leandros
authors.initials: L
authors.lastname: Lazaros
authors.forename: Nectaria
authors.initials: N
authors.lastname: Xita
authors.forename: Apostolos
authors.initials: A
authors.lastname: Kaponis
authors.forename: Elissavet
authors.initials: E
authors.lastname: Hatzi
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Plachouras
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Sofikitis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zikopoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Georgiou
mesh_terms: D000328:Adult; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009845:Oligospermia / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics* / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D001141:Aromatase