• PMID: 20356899
• Gene Name: ESX1
• Condition: Azoospermia, impaired spermatogenesis
• Association: Associated
• Population size: 81
• Population details: 81 azoospermic cases, 33 obstructive azoospermia, 18 hypospermatogenesis, 2 incomplete maturation arrest (MA)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: ESX1
• Other associated phenotypes: Azoospermia, impaired spermatogenesis

ESX1 gene expression as a robust marker of residual spermatogenesis in azoospermic men

Bonaparte E, Moretti M, Colpi GM, Nerva F, Contalbi G, Vaccalluzzo L, Tabano S, Grati FR, Gazzano G, Sirchia SM, Simoni G, Gallina A, Miozzo M.

BACKGROUND: It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice. METHODS: We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS: The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS: ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies. FAU - Bonaparte, E AU - Bonaparte E AD - Department of Medicine, Surgery and Dentistry, Medical Genetics Unit, Università degli Studi di Milano, 20142 Milano, Italy. FAU - Moretti, M AU - Moretti M FAU - Colpi, G M AU - Colpi GM FAU - Nerva, F AU - Nerva F FAU - Contalbi, G AU - Contalbi G FAU - Vaccalluzzo, L AU - Vaccalluzzo L FAU - Tabano, S AU - Tabano S FAU - Grati, F R AU - Grati FR FAU - Gazzano, G AU - Gazzano G FAU - Sirchia, S M AU - Sirchia SM FAU - Simoni, G AU - Simoni G FAU - Gallina, A AU - Gallina A