Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality

Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality Full article

Journal

Oncotarget
ISSN: 1949-2553

Output data

Year: 2017, Volume: 8, Number: 51, Pages: 88294-88307 Pages count : 14 DOI: 10.18632/oncotarget.18331

Tags

5-hydroxymethylcytosine; Pathology Section; human spermatogenesis; semen quality; sperm DNA fragmentation; testicular spermatogenic cells

Authors

Efimova Olga A. ^1,2 , Pendina Anna A. ^1,2,3 , Tikhonov Andrei V. ^1,2,3 , Parfenyev Sergey E. ² , Mekina Irina D. ¹ , Komarova Evgeniia M. ¹ , Mazilina Mariia A. ^1,2 , Daev Eugene V. ² , Chiryaeva Olga G. ^1,4,5 , Galembo Ilona A. ³ , Krapivin Mikhail I. ² , Glotov Oleg S. ^1,2 , Stepanova Irina S. ^6,7 , Shlykova Svetlana A. ⁸ , Kogan Igor Yu. ¹ , Gzgzyan Alexander M. ^1,2 , Kuznetzova Tatyana V. ^1,2 , Baranov Vladislav S. ^1,2

Affiliations

1	D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia; St. Petersburg State University, St. Petersburg, Russia
2	St. Petersburg State University, St. Petersburg, Russia
3	Center for Medical Genetics, St. Petersburg, Russia
4	St. Petersburg State Pediatric Medical University, St. Petersburg, Russia
5	S.M. Kirov Military Medical Academy, St. Petersburg, Russia
6	Institute of Cytology RAS, St. Petersburg, Russia
7	Aimed Clinic, St. Petersburg, Russia
8	AVA-Peter Clinic, St. Petersburg, Russia

We performed immunofluorescent analysis of DNA hydroxymethylation and methylation in human testicular spermatogenic cells from azoospermic patients and ejaculated spermatozoa from sperm donors and patients from infertile couples. In contrast to methylation which was present throughout spermatogenesis, hydroxymethylation was either high or almost undetectable in both spermatogenic cells and ejaculated spermatozoa. On testicular cytogenetic preparations, 5-hydroxymethylcytosine was undetectable in mitotic and meiotic chromosomes, and was present exclusively in interphase spermatogonia Ad and in a minor spermatid population. The proportions of hydroxymethylated and non-hydroxymethylated diploid and haploid nuclei were similar among samples, suggesting that the observed alterations of 5-hydroxymethylcytosine patterns in differentiating spermatogenic cells are programmed. In ejaculates, a few spermatozoa had high 5-hydroxymethylcytosine level, while in the other ones hydroxymethylation was almost undetectable. The percentage of highly hydroxymethylated (5-hydroxymethylcytosine-positive) spermatozoa varied strongly among individuals. In patients from infertile couples, it was higher than in sperm donors (P<0.0001) and varied in a wider range: 0.12-21.24% versus 0.02-0.46%. The percentage of highly hydroxymethylated spermatozoa correlated strongly negatively with the indicators of good semen quality - normal morphology (r=-0.567, P<0.0001) and normal head morphology (r=-0.609, P<0.0001) - and strongly positively with the indicator of poor semen quality: sperm DNA fragmentation (r=0.46, P=0.001). Thus, the immunocytochemically detected increase of 5hmC in individual spermatozoa is associated with infertility in a couple and with deterioration of sperm parameters. We hypothesize that this increase is not programmed, but represents an induced abnormality and, therefore, it can be potentially used as a novel indicator of semen quality.

Efimova O.A. , Pendina A.A. , Tikhonov A.V. , Parfenyev S.E. , Mekina I.D. , Komarova E.M. , Mazilina M.A. , Daev E.V. , Chiryaeva O.G. , Galembo I.A. , Krapivin M.I. , Glotov O.S. , Stepanova I.S. , Shlykova S.A. , Kogan I.Y. , Gzgzyan A.M. , Kuznetzova T.V. , Baranov V.S.
Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality
Oncotarget. 2017. V.8. N51. P.88294-88307. DOI: 10.18632/oncotarget.18331 WOS Scopus

Web of science:	WOS:000413585600007
Scopus:	2-s2.0-85031929026

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Web of science	28
Scopus	31