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Journal of Assisted Reproduction and Genetics

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Open Access 17-07-2024 | Infertility | Genetics

Male infertility is associated with differential DNA methylation signatures of the imprinted gene GNAS and the non-imprinted gene CEP41

Authors: Suheyla Esra Ozkocer, Ismail Guler, Asiye Ugras Dikmen, Nuray Bozkurt, Nuray Varol, Ece Konac

Published in: Journal of Assisted Reproduction and Genetics | Issue 9/2024

Abstract

Purpose

To investigate whether the DNA methylation profiles of GNAS(20q13.32), MEST(7q32.2), MESTIT1(7q32.2), IGF2(11p15.5), H19 (7q32.2), and CEP41(7q32.2) genes are related to the transcriptomic and epigenomic etiology of male infertility.

Methods

The DNA methylation levels of spermatozoa were obtained from fertile (n = 30), oligozoospermic (n = 30), and men with normal sperm count (n = 30). The methylation status of each CpG site was categorized as hypermethylated or hypomethylated. Expression levels of target gene transcripts were determined using real-time PCR.

Results

The oligozoospermia showed a higher frequency of hypermethylation at GNASAS 1st, 3rd, and 5th CpG dinucleotides (66.7%, 73.3%, 73.3%) compared to the fertile group (33.3%, 33.3%, 40%, respectively). The normal sperm count exhibited a higher frequency of hypermethylation at the 3rd CpG of CEP41 (46.7%) than the fertile group (16.7%). Normal sperm count was predicted by CEP41 hypermethylation (OR = 1.750, 95%CI 1.038–2.950) and hypermethylation of both CEP41 and GNASAS (OR = 2.389, 95%CI 1.137–5.021). Oligozoospermia was predicted solely by GNASAS hypermethylation (OR = 2.460, 95%CI 1.315–4.603). In sperms with decreased IGF2 expression in the fertile group, we observed hypomethylation in the 2nd CpG of IGF2 antisense (IFG2AS), and hypermethylation in the 1st, 2nd, and 4th CpGs of H19. No significant relationship was found between IGF2 expression and methylation status of IGF2AS and H19 in infertile groups.

Conclusion

The disappearance of the relationship between IGF2 expression and IGF2AS and H19 methylations in the infertile group provides new information regarding the disruption of epigenetic programming during spermatogenesis. A better understanding of sperm GNASAS and CEP41 hypermethylation could advance innovative diagnostic markers for male infertility.

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Title: Male infertility is associated with differential DNA methylation signatures of the imprinted gene GNAS and the non-imprinted gene CEP41
Authors: Suheyla Esra Ozkocer
Ismail Guler
Asiye Ugras Dikmen
Nuray Bozkurt
Nuray Varol
Ece Konac
Publication date: 17-07-2024
Publisher: Springer US
Keywords: Infertility
Infertility
Epigenetics
Published in: Journal of Assisted Reproduction and Genetics / Issue 9/2024
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-024-03202-w

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Male infertility is associated with differential DNA methylation signatures of the imprinted gene GNAS and the non-imprinted gene CEP41

Abstract

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