Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment
Por:
Cervan-Martin, M, Bossini-Castillo, L, Rivera-Egea, R, Garrido, N, Lujan, S, Romeu, G, Santos-Ribeiro, S, Castilla, JA, Gonzalvo, MC, Clavero, A, Vicente, FJ, Guzman-Jimenez, A, Costa, C, Llinares-Burguet, I, Khantham, C, Burgos, M, Barrionuevo, FJ, Jimenez, R, Sanchez-Curbelo, J, Lopez-Rodrigo, O, Peraza, MF, Pereira-Caetano, I, Marques, PI, Carvalho, F, Barros, A, Bassas, L, Seixas, S, Goncalves, J, Larriba, S, Lopes, AM, Palomino-Morales, RJ, Carmona, FD, IVIRMA Grp, Lisbon Clinical Grp
Publicada:
1 ene 2021
Resumen:
Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffected controls to evaluate whether five single-nucleotide polymorphisms (SNPs), previously associated with reduced fertility in Hutterites, are also involved in the genetic susceptibility to idiopathic SpF and specific clinical entities. A significant difference in the allele frequencies of USP8-rs7174015 was observed under the recessive model between the NOA group and both the control group (p = 0.0226, OR = 1.33) and the SO group (p = 0.0048, OR = 1.78). Other genetic associations for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO and between TUSC1-rs10966811 and testicular sperm extraction (TESE) success in the context of NOA were observed. In silico analysis of functional annotations demonstrated cis-eQTL effects of such SNPs likely due to the modification of binding motif sites for relevant transcription factors of the spermatogenic process. The findings reported here shed light on the molecular mechanisms leading to severe phenotypes of idiopathic male infertility, and may help to better understand the contribution of the common genetic variation to the development of these conditions.
Filiaciones:
Cervan-Martin, M:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
Bossini-Castillo, L:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
Rivera-Egea, R:
IVIRMA Valencia, Androl Lab & Sperm Bank, Valencia 46015, Spain
IVI Fdn, Hlth Res Inst La Fe, Valencia 46026, Spain
Garrido, N:
IVI Fdn, Hlth Res Inst La Fe, Valencia 46026, Spain
Hosp Univ & Politecn La Fe, Serv Urol, Valencia 46026, Spain
Inst Invest Sanitaria La Fe IIS La Fe, Valencia 46026, Spain
Lujan, S:
Hosp Univ & Politecn La Fe, Serv Urol, Valencia 46026, Spain
Inst Invest Sanitaria La Fe IIS La Fe, Valencia 46026, Spain
Romeu, G:
Hosp Univ & Politecn La Fe, Serv Urol, Valencia 46026, Spain
Inst Invest Sanitaria La Fe IIS La Fe, Valencia 46026, Spain
Santos-Ribeiro, S:
Inst Invest Sanitaria La Fe IIS La Fe, Valencia 46026, Spain
IVI RMA Lisbon, P-1800282 Lisbon, Portugal
Univ Lisbon, Dept Obstet & Gynecol, Fac Med, P-1649028 Lisbon, Portugal
Castilla, JA:
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
HU Virgen Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada 18014, Spain
CEIFER Biobanco NextClin, Granada 18004, Spain
Gonzalvo, MC:
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
HU Virgen Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada 18014, Spain
Clavero, A:
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
HU Virgen Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada 18014, Spain
Vicente, FJ:
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Guzman-Jimenez, A:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Costa, C:
Univ Porto I3S, Inst Invest & Inovacao Saude, P-4200135 Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Porto, Portugal
Llinares-Burguet, I:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Khantham, C:
Chiang Mai Univ, Dept Pharmaceut Sci, Fac Pharm, Chiang Mai 50200, Thailand
Burgos, M:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Barrionuevo, FJ:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Jimenez, R:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Sanchez-Curbelo, J:
Fundacio Puigvert, Androl Serv, Lab Seminol & Embryol, Barcelona 08025, Spain
Lopez-Rodrigo, O:
Fundacio Puigvert, Androl Serv, Lab Seminol & Embryol, Barcelona 08025, Spain
Peraza, MF:
Fundacio Puigvert, Androl Serv, Lab Seminol & Embryol, Barcelona 08025, Spain
Pereira-Caetano, I:
Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, P-1649016 Lisbon, Portugal
Marques, PI:
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Univ Porto I3S, Inst Invest & Inovacao Saude, P-4200135 Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Porto, Portugal
Carvalho, F:
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Univ Porto, Fac Med, Dept Patol, Serv Genet, P-4200319 Porto, Portugal
Barros, A:
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Univ Porto, Fac Med, Dept Patol, Serv Genet, P-4200319 Porto, Portugal
Seixas, S:
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Univ Porto I3S, Inst Invest & Inovacao Saude, P-4200135 Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Porto, Portugal
Goncalves, J:
Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, P-1649016 Lisbon, Portugal
Nova Med Sch, ToxOmics Ctr Toxicogen & Saude Humana, P-1169056 Lisbon, Portugal
Larriba, S:
Bellvitge Biomed Res Inst IDIBELL, Human Mol Genet Grp, Barcelona 08908, Spain
Lopes, AM:
HU Virgen Nieves, UGC Urol, Granada 18014, Spain
Univ Porto I3S, Inst Invest & Inovacao Saude, P-4200135 Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200135 Porto, Portugal
Palomino-Morales, RJ:
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
Univ Granada, Dept Bioquim & Biol Mol 1, Granada 18071, Spain
Carmona, FD:
Univ Granada, Dept Genet, Granada 18016, Spain
Univ Granada, Inst Biotecnol, Granada 18016, Spain
Inst Invest Biosanitaria Ibs GRANADA, Granada 18012, Spain
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