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.

Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation

“…Regarding CYP19(TTTA) 7 allele, significant associations with lower estrone, estrone sulphate and estradiol concentrations have been reported [24,25]. This allele has been also associated with lower sperm concentration and motility in normozoospermic and oligospermic men, due to potential impairment of the aromatase activity [21].…”

“…The CYP19 (TTTA) n repeat region was amplified by polymerase chain reaction (PCR), according to a protocol previously described [17,20,21]. The PCR products were separated by 10% polyacrylamide gel electrophoresis followed by silver staining, and the number of TTTA repeats in each allele was analysed by sequencing the appropriate PCR products [20].…”

“…To analyse the association of this polymorphism with ovarian response to standard gonadotrophin stimulation, the CYP19 (TTTA)n alleles were divided into 2 subgroups using the (TTTA) 9 allele as a cut-off point (based on the median number of TTTA repeats): short CYP19 alleles with nine or fewer TTTA repeats and long CYP19 alleles with more than nine TTTA repeats. The same cut-off allele has been used in previous studies exploring the distribution of the CYP19 (TTTA)n polymorphism [16,20,21].…”

Teasing out the role of aromatase in the healthy and diseased testis

“…64 As no change in Sertoli cell number has been reported 6,64 (although Sertoli cell function has yet to be tested), it appears this is a result of significant reductions in round and elongated spermatid CYP19A1 gene polymorphism, which impairs aromatase activity, and reduced sperm motility. 48 It is well recognized that estrogens are essential for luminal fluid secretion and re-absorption to generate an optimum environment for spermiation and sperm motility acquisition. 49 The fact that aromatase has been immunolocalized to human efferent ductules, the site of luminal fluid re-absorption, and the proximal ductus epididymis, which aids in sperm motility acquisition, further supports this established link and suggests that spermatozoa themselves may be capable of regulating local estrogen concentrations via aromatase.…”

Hyperestrogenism and low serum testosterone-17β-estradiol ratio are associated with non-bacterial male accessory gland inflammation

“…18 In another experimental model, chronic treatment with estrogens results in the activation of metalloproteinases 2,7,9 in the lateral lobe of the prostate and increase of leukocyte infiltrate. 19 Other conceivable causes could be represented by the functional alterations of aromatase, the enzyme responsible for the conversion of T into E2, which are more frequent in infertile patients, 20 or the TT reduction associated with the psychological stress which is another important characteristic of patients with chronic prostate inflammation. 21,22 In clinical practice, for infertile patients with a reduction of T:E2 ratio (threshold value <10), it may be suggested that the pharmacological therapy with aromatase inhibitors (testolactone, anastrozole, letrozole) which represent a class of drugs used off label, 23 but for which there is no documented evidence in the literature regarding the clinical model of chronic prostatitis or MAGI.…”