Journal of Personalized Medicine (Dec 2020)
Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment
- Miriam Cerván-Martín,
- Lara Bossini-Castillo,
- Rocío Rivera-Egea,
- Nicolás Garrido,
- Saturnino Luján,
- Gema Romeu,
- Samuel Santos-Ribeiro,
- IVIRMA Group,
- Lisbon Clinical Group,
- José A. Castilla,
- M. Carmen Gonzalvo,
- Ana Clavero,
- F. Javier Vicente,
- Andrea Guzmán-Jiménez,
- Cláudia Costa,
- Inés Llinares-Burguet,
- Chiranan Khantham,
- Miguel Burgos,
- Francisco J. Barrionuevo,
- Rafael Jiménez,
- Josvany Sánchez-Curbelo,
- Olga López-Rodrigo,
- M. Fernanda Peraza,
- Iris Pereira-Caetano,
- Patricia I. Marques,
- Filipa Carvalho,
- Alberto Barros,
- Lluís Bassas,
- Susana Seixas,
- João Gonçalves,
- Sara Larriba,
- Alexandra M. Lopes,
- Rogelio J. Palomino-Morales,
- F. David Carmona
Affiliations
- Miriam Cerván-Martín
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Lara Bossini-Castillo
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Rocío Rivera-Egea
- Andrology Laboratory and Sperm Bank, IVIRMA Valencia, 46015 Valencia, Spain
- Nicolás Garrido
- IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain
- Saturnino Luján
- Servicio de Urología, Hospital Universitari i Politecnic La Fe e Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Gema Romeu
- Servicio de Urología, Hospital Universitari i Politecnic La Fe e Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Samuel Santos-Ribeiro
- IVI-RMA Lisbon, 1800-282 Lisbon, Portugal
- IVIRMA Group
- Lisbon Clinical Group
- José A. Castilla
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- M. Carmen Gonzalvo
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Ana Clavero
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- F. Javier Vicente
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Andrea Guzmán-Jiménez
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Cláudia Costa
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- Inés Llinares-Burguet
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Chiranan Khantham
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Miguel Burgos
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Francisco J. Barrionuevo
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Rafael Jiménez
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- Josvany Sánchez-Curbelo
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Olga López-Rodrigo
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- M. Fernanda Peraza
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Iris Pereira-Caetano
- Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- Patricia I. Marques
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- Filipa Carvalho
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- Alberto Barros
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- Lluís Bassas
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Susana Seixas
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- João Gonçalves
- Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal
- Sara Larriba
- Human Molecular Genetics Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Alexandra M. Lopes
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (I3S), 4200-135 Porto, Portugal
- Rogelio J. Palomino-Morales
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- F. David Carmona
- Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, 18016 Granada, Spain
- DOI
- https://doi.org/10.3390/jpm11010022
- Journal volume & issue
-
Vol. 11,
no. 1
p. 22
Abstract
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.
Keywords
- SNPs
- genetic association analysis
- impaired spermatogenesis
- non-obstructive azoospermia
- severe oligospermia
- infertility