Alterations of testis-specific promoter methylation in cell-free seminal deoxyribonucleic acid of idiopathic nonobstructive azoospermic men with different testicular phenotypes

This study demonstrates the feasibility of quantifying human testis-specific promoter methylation from cell-free seminal DNA, and its predictive potential for sperm retrieval in nonobstructive azoospermia.

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Volume 106, Issue 6, Pages 1331-1337

Authors:

Chunlin Wu, Ph.D., Xiaofang Ding, Ph.D., Huiping Tan, Ph.D., Honggang Li, Ph.D., Chengliang Xiong, M.D.

Abstract:

Objective

To explore the feasibility of quantification of testicular DNA methylation from cell-free seminal DNA (cfsDNA), and analyze promoter methylation alterations in men with idiopathic nonobstructive azoospermia (NOA).

Design

Comparison between testicular DNA and paired cfsDNA, and among NOA patients with different testicular phenotypes.

Setting

Academic research institute and andrology practice.

Patient(s)

Eighty-eight idiopathic NOA patients with different testicular phenotypes and 24 normozoospermic men.

Intervention(s)

Testicular biopsies and semen.

Main Outcome Measure(s)

Five testis-specific methylated promoters were selected. Promoter methylation was quantified using MethyLight in testicular DNA and paired cfsDNA, and the mRNA level was determined by real-time quantitative polymerase chain reaction.

Result(s)

Correlations of methylation of the selected five promoters between testicular DNA and paired cfsDNA were observed; and promoter methylation was negatively related to the messenger RNA level in testis. The cfsDNA methylation of these promoters showed different dynamic changes among the subtypes of NOA and normozoospermia. Among them, CCNA1 and DMRT1 promoter methylation in the hypospermatogenesis group was higher than in other groups and showed diagnostic potential for the patient with hypospermatogenesis.

Conclusion(s)

Cell-free seminal DNA could be a novel, noninvasive biomarker for the detection of testicular epigenetic aberrations. Epigenetic information in cfsDNA related to spermatogenesis may serve to predict successful testicular sperm retrieval in NOA patients.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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