HLA-DQB1 as a potential prognostic biomarker of hormonal therapy in patients with non-obstructive azoospermia.

Autor: Malcher A; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address: agnieszka.malcher@igcz.poznan.pl., Kamieniczna M; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland., Rozwadowska N; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland., Stokowy T; IT Division, University of Bergen, Bergen, Norway., Berger A; Department of Cell Biology, University of Medical Sciences, Poznan, Poland; Center of Obstetrics, Gynecology and Infertility Treatment, Poznan, Poland., Jedrzejczak P; Department of Cell Biology, University of Medical Sciences, Poznan, Poland; Center of Obstetrics, Gynecology and Infertility Treatment, Poznan, Poland., Wolski JK; nOvum Fertility Clinic, Warszawa, Poland., Kurpisz M; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address: maciej.kurpisz@igcz.poznan.pl.
Jazyk: angličtina
Zdroj: Reproductive biology [Reprod Biol] 2024 Dec; Vol. 24 (4), pp. 100949. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1016/j.repbio.2024.100949
Abstrakt: The gonadotropin treatment of infertile men may improve spermatogenesis and lead to sperm cell production, however, only a small fraction of treated patients positively responds to such therapy. To identify individual treatment prognostic biomarkers associated with responsiveness to gonadotropins, we compared the gene expression profiles of testicular oligobiopsies from 3 patients with non-obstructive azoospermia (NOA) who positively responded to therapy with a combination of human chorionic gonadotropin and recombinant follicle-stimulating hormone (hCG/rFSH) to those of 3 non-responders. We used Affymetrix Human Gene 1.0 ST microarrays. The results of the microarray evaluation were validated by the qPCR technique while gene variants of the HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) were subsequently sequenced. In our microarrays, we have identified most significantly 5 transcripts with different expression levels in responders versus non-responders groups. Our interest has been primarily focused on the transcript associated with the HLA-DQB1 gene. Because the expression of this gene was up-regulated in the non-responding patients and only patients with heterozygotic alleles of HLA-DQB1 turned out to be positive to gonadotropin therapy, we suggest that this gene may be a biomarker of potential significance for the gonadotropin treatment of male infertility. We also compared the testicular gene expression profile in one individual before and after gonadotropin treatment. In the re-biopsied sample, we have identified over 600 genes that showed differences in testicular expression; some of these genes are critical for spermiogenesis. Thus, we documented that the applied gonadotropins successfully stimulated the spermatogenetic wave in patients with NOA.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE