• PMID: 23001776
• Gene Name: CYP19A1
• Condition: Oligozoospermic, normozoospermic, sperm concentration and motility
• Association: AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms had a synergistic effect on sperm concentration and motility.
• Mutation: AR(CAG)(n), CYP19(TTTA)(n) polymorphisms
• Population size: 450
• Population details: 450 (200 oligozoospermic, 250 normozoospermic men )
• Sex: Male
• Infertility type: Male infertility
• Associated genes: AR, CYP19
• Other associated phenotypes: Oligozoospermic, normozoospermic, sperm concentration and motility

Semen quality is influenced by androgen receptor and aromatase gene synergism

Lazaros L, Xita N, Takenaka A, Sofikitis N, Makrydimas G, Stefos T, Kosmas I, Zikopoulos K, Hatzi E, Georgiou I.

STUDY QUESTION: Does synergism between AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms influence the quality of sperm? SUMMARY ANSWER: AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms had a synergistic effect on sperm concentration and motility. WHAT IS KNOWN ALREADY: Androgens exert their action in the testicular tissue by binding to androgen receptor (AR), while their action is mediated by the aromatase P450 enzyme (CYP19). AR(CAG)(n) alleles are associated with sperm motility and CYP19(TTTA)(n) allelic variants have implications for sperm concentration and motility. STUDY DESIGN, SIZE, DURATION: Two hundred oligozoospermic and 250 normozoospermic men who presented for infertility investigation were examined during a period of 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conventional semen analysis was performed. DNA was extracted from spermatozoa and both polymorphisms were genotyped by polymerase chain reaction. Serum hormone levels were determined. MAIN RESULTS AND THE ROLE OF CHANCE: Six combined genotypes were identified between the 18 AR(CAG)(n) alleles with 12-32 repeats and the 6 CYP19(TTTA)(n) alleles with 7-12 repeats. A gradual reduction in the sperm concentration (10(6)/ml) and motility (%) from long AR allele-non-CYP19(TTTA)(7) allele carriers to long AR allele-CYP19(TTTA)(7) homozygotes and from short AR allele-non-CYP19(TTTA)(7) carriers to short AR allele-CYP19(TTTA)(7) homozygotes was observed in normozoospermic men (means ± SD; concentration: 93 ± 53.1 versus 65 ± 48.6 and 85 ± 60.1 versus 37 ± 17.2l, P < 0.002; motility: 63 ± 10.3 versus 55 ± 14.5 and 52 ± 19.6 versus 41 ± 13.7, P < 0.001, respectively). Similar associations were observed in oligozoospermic men (concentration: 10 ± 4.2 versus 9 ± 5.9 and 10 ± 6.3 versus 6 ± 3.1, P < 0.03; motility: 47 ± 17.1 versus 39 ± 6.2 and 39 ± 22 versus 27 ± 18.3, P < 0.003, respectively). The above associations of the combined genotypes with sperm concentration and motility were confirmed in the total study population (P < 0.006 and P < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Our study population was limited to Greek Caucasian adult males, residents of Northwest Greece. WIDER IMPLICATIONS OF THE FINDINGS: The confirmation of our findings in other populations would verify the significance of AR and CYP19 genes for spermatogenesis. STUDY FUNDING/COMPETING INTERESTS: This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. The authors declare no conflicts of interest. FAU - Lazaros, L AU - Lazaros L AD - Genetics and IVF Unit, Department of Obstetrics and Gynecology, Medical School, Ioannina University, Ioannina, Greece. FAU - Xita, N AU - Xita N FAU - Takenaka, A AU - Takenaka A FAU - Sofikitis, N AU - Sofikitis N FAU - Makrydimas, G AU - Makrydimas G FAU - Stefos, T AU - Stefos T FAU - Kosmas, I AU - Kosmas I FAU - Zikopoulos, K AU - Zikopoulos K FAU - Hatzi, E AU - Hatzi E