RESUMO
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.
Assuntos
Aromatase/genética , Variação Genética , Oligospermia/enzimologia , Oligospermia/genética , Contagem de Espermatozoides , Motilidade dos Espermatozoides/genética , Motilidade dos Espermatozoides/fisiologia , Adulto , Alelos , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/genética , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Repetições de Microssatélites , Oligospermia/patologia , Espermatogênese/genética , Espermatogênese/fisiologiaRESUMO
Paraoxonase (PON) is a high-density lipoprotein-associated enzyme that prevents low-density lipoprotein oxidation. PON proteins, localized in the seminiferous tubules and in spermatozoa, have been implicated in the pathogenesis of male infertility. In the present study, we sought to explore the contribution of the PON gene variants to sperm parameters. One hundred twenty oligospermic and 170 normozoospermic men were examined during infertility investigation. DNA was extracted from spermatozoa, and the PON1(L/M) 55, PON1(Q/R) 192, and PON2(S/C) 311 polymorphisms were genotyped by polymerase chain reaction and digestion with restriction enzymes. The analysis revealed that oligospermic men presented PON1 55L/L, PON1 192Q/Q, and PON2 311S/S genotypes less frequently than normozoospermic men (P < .01, P < .01, and P < .001, respectively), whereas the PON1 55M, PON1 192R, and PON2 311C alleles were significantly increased in oligospermic men (P < .004, P < .008, and P < .008, respectively). The presence of PON1 55L allele was associated with higher sperm motility in oligospermic men (P < .001), in normozoospermic men (P < .01), and in the total study population (P < .01), and the PON1 192Q allele was associated with higher sperm motility in oligospermic men (P < .01), in normozoospermic men (P < .04) and in the total study population (P < .03). On the other hand, the PON2 311S was associated with higher sperm concentration in oligospermic men (P < .03), in normozoospermic men (P < .008), and in the total study population (P < .001). In our series, the PON1 55M and PON1 192R alleles were associated with decreased sperm motility whereas the PON2 311C allele was associated with decreased concentration, supporting the significance of PON genes in semen quality.