LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset
LIN28B is an RNA-binding protein that acts as a post-transcriptional regulator of genes involved in developmental timing and self-renewal through its interaction with let-7 miRNAs. Large-scale genomic studies have strongly implicated SNPs in LIN28B with male puberty timing. In addition, the occurren...
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Bioscientifica
2025-05-01
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| Series: | Endocrine Connections |
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| Online Access: | https://ec.bioscientifica.com/view/journals/ec/14/6/EC-25-0044.xml |
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| author | María Cecilia Lardone Marina Díaz-Fontdevila Eliana Ortiz Germán Iñiguez Pamela Inostroza Cristóbal Espinoza Mauricio Ebensperger Kristian Almstrup Andrea Castro |
| author_facet | María Cecilia Lardone Marina Díaz-Fontdevila Eliana Ortiz Germán Iñiguez Pamela Inostroza Cristóbal Espinoza Mauricio Ebensperger Kristian Almstrup Andrea Castro |
| author_sort | María Cecilia Lardone |
| collection | DOAJ |
| description | LIN28B is an RNA-binding protein that acts as a post-transcriptional regulator of genes involved in developmental timing and self-renewal through its interaction with let-7 miRNAs. Large-scale genomic studies have strongly implicated SNPs in LIN28B with male puberty timing. In addition, the occurrence of late puberty is linked to diminished semen quality in adult life. Therefore, we aimed to study the association of puberty-linked LIN28B genetic variants with semen parameters, reproductive hormones and the spermatozoa expression of the LIN28B/Let-7 axis in idiopathic oligozoospermic men. One hundred and eleven oligozoospermic (cases) and 258 men with normal sperm concentration (controls) were genotyped for five LIN28B SNPs (rs7759938, rs395962, rs314268, rs314277 and rs314280). The abundance of the LIN28B transcript, let-7a and let-7c miRNAs were measured by qRT-PCR in RNA isolated from purified sperm. Serum blood samples were analysed for reproductive hormones. Lower abundance of the LIN28B transcript and higher expression of let-7c were observed in cases (P < 0.001). Furthermore, rs395962_T was associated with a reduced abundance of the LIN28B transcript in cases (dominant: P = 0.032). On the other side, we observed a positive association of rs314277_A (Additive: P = 0.024), rs7759938_C (dominant: P = 0.025) and rs314280_A (dominant: P = 0.024) with total testosterone levels in cases. The decreased transcript abundance of LIN28B in sperm of idiopathic oligozoospermic men and its association with SNPs known to affect the onset of puberty and total testosterone levels suggests a role for LIN28B in the primary impairment of spermatogenesis through its expression in early germ cells or regulating the testicular biosynthesis of testosterone at a central level. Therefore, our results provide a potential mechanistic link between the regulation of pubertal timing and adult testicular function. |
| format | Article |
| id | doaj-art-6bb9eb94a4d2408bb8b4d2ae8f4b3313 |
| institution | OA Journals |
| issn | 2049-3614 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Bioscientifica |
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| series | Endocrine Connections |
| spelling | doaj-art-6bb9eb94a4d2408bb8b4d2ae8f4b33132025-08-20T02:02:26ZengBioscientificaEndocrine Connections2049-36142025-05-0114610.1530/EC-25-00441LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onsetMaría Cecilia Lardone0Marina Díaz-Fontdevila1Eliana Ortiz2Germán Iñiguez3Pamela Inostroza4Cristóbal Espinoza5Mauricio Ebensperger6Kristian Almstrup7Andrea Castro8Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkInstitute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, ChileLIN28B is an RNA-binding protein that acts as a post-transcriptional regulator of genes involved in developmental timing and self-renewal through its interaction with let-7 miRNAs. Large-scale genomic studies have strongly implicated SNPs in LIN28B with male puberty timing. In addition, the occurrence of late puberty is linked to diminished semen quality in adult life. Therefore, we aimed to study the association of puberty-linked LIN28B genetic variants with semen parameters, reproductive hormones and the spermatozoa expression of the LIN28B/Let-7 axis in idiopathic oligozoospermic men. One hundred and eleven oligozoospermic (cases) and 258 men with normal sperm concentration (controls) were genotyped for five LIN28B SNPs (rs7759938, rs395962, rs314268, rs314277 and rs314280). The abundance of the LIN28B transcript, let-7a and let-7c miRNAs were measured by qRT-PCR in RNA isolated from purified sperm. Serum blood samples were analysed for reproductive hormones. Lower abundance of the LIN28B transcript and higher expression of let-7c were observed in cases (P < 0.001). Furthermore, rs395962_T was associated with a reduced abundance of the LIN28B transcript in cases (dominant: P = 0.032). On the other side, we observed a positive association of rs314277_A (Additive: P = 0.024), rs7759938_C (dominant: P = 0.025) and rs314280_A (dominant: P = 0.024) with total testosterone levels in cases. The decreased transcript abundance of LIN28B in sperm of idiopathic oligozoospermic men and its association with SNPs known to affect the onset of puberty and total testosterone levels suggests a role for LIN28B in the primary impairment of spermatogenesis through its expression in early germ cells or regulating the testicular biosynthesis of testosterone at a central level. Therefore, our results provide a potential mechanistic link between the regulation of pubertal timing and adult testicular function.https://ec.bioscientifica.com/view/journals/ec/14/6/EC-25-0044.xmllin28bmirna let-7oligozoospermialin28b genetic polymorphismsmale infertilitymale puberty |
| spellingShingle | María Cecilia Lardone Marina Díaz-Fontdevila Eliana Ortiz Germán Iñiguez Pamela Inostroza Cristóbal Espinoza Mauricio Ebensperger Kristian Almstrup Andrea Castro LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset Endocrine Connections lin28b mirna let-7 oligozoospermia lin28b genetic polymorphisms male infertility male puberty |
| title | LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| title_full | LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| title_fullStr | LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| title_full_unstemmed | LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| title_short | LIN28B expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| title_sort | lin28b expression is downregulated in mature spermatozoa of oligozoospermic men and associates with genetic variants previously linked to pubertal onset |
| topic | lin28b mirna let-7 oligozoospermia lin28b genetic polymorphisms male infertility male puberty |
| url | https://ec.bioscientifica.com/view/journals/ec/14/6/EC-25-0044.xml |
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