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Methylation Status of cAMP-responsive Element Modulator (CREM) Gene in Infertile Men and Its Association with Sperm Parameters

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Abstract

The methylation pattern of non-imprinting genes was little studied, although it is widely known that the abnormal methylation levels of imprinting genes are associated with different forms of male infertility. The purpose of this research was to assess the CREM gene's methylation status and seminal characteristics in infertile individuals who were potential intracytoplasmic sperm injection (ICSI) candidates. A total of 45 semen samples (15 normospermia, 15 asthenospermia, and 15 oligoasthenoteratospermia) were examined. Using aniline blue (AB) staining, we carried out conventional semen analysis, chromatin quality, and sperm maturity testing. DNA was taken from semen samples, and all isolated DNA was assessed using Nanodrop and gel electrophoresis. A quantitative methylation-specific polymerase chain reaction (Q-MSP) approach was used to quantify the methylation at the DMRs of the CREM gene. According to our findings, sperm count (P=0.012), concentration (P= 0.019), motility (P=0.006), progression (P=0.006), and normal morphology (P=0.004) were all inversely correlated with abnormal sperm chromatin condensation. Additionally, we noted that the methylation level of the CREM gene was considerably more significant in the oligoasthenoteratospermia group compared to the asthenospermia and normospermia groups (P<0.05). Additionally, sperm count (P=0.043), progression (P=0.026), and normal morphology (P=0.024) were all inversely linked with CREM methylation. Overall, the abnormal CREM methylation patterns have a negative impact on sperm parameters. Additionally, the CREM gene's DNA methylation status may serve as an epigenetic indicator of male infertility.

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Acknowledgment

The authors greatly thank Mr. Amin Jalilvand, Dr. Amir Hossein Norooznezhad, and Dr. Fatemeh Yarmohammadi for their assistance in editing the final version of this manuscript.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Fouzieh Karami Hezarcheshmeh, Parichehreh Yaghmaei & Nasim Hayati Roodbari

  2. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Kheirollah Yari

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  1. Fouzieh Karami Hezarcheshmeh
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Contributions

F.K. contributed to sample collection and performed the experiments, K.Y., P.Y., and N. H.R. contributed to the study design, interpretation of the data, and wrote the manuscript. All authors performed the review, editing, preparation and approval of the manuscript.

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Correspondence to Kheirollah Yari.

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The Research Ethics Committee at the Deputy of Research of Islamic Azad University approved the study protocol (IR.IAU.SRB.REC.1401.183).

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All subjects gave written informed consent in accordance with the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations in the declaration of Helsinki.

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Karami Hezarcheshmeh, F., Yaghmaei, P., Hayati Roodbari, N. et al. Methylation Status of cAMP-responsive Element Modulator (CREM) Gene in Infertile Men and Its Association with Sperm Parameters. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01510-1

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