Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders

K. Shiraishi, A. Shindo, A. Harada, H. Kurumizaka, H. Kimura, Y. Ohkawa, H. Matsuyama

Research output: Contribution to journalArticle

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Abstract

Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin's solution-fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and PCNA expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene/leptotene-stage primary spermatocytes, especially during germinal stages VI–X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p < 0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p < 0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy. Different from other testis-specific histones, which are often expressed during the histone-to-protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.

Original languageEnglish
Pages (from-to)158-165
Number of pages8
JournalAndrology
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 2018

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Azoospermia
Spermatogenesis
Histones
Testis
Proliferating Cell Nuclear Antigen
Spermatocytes
Germ Cells
Meiotic Prophase I
Oligospermia
Salvage Therapy
Microdissection
Spermatogonia
Protamines
Nucleosomes
Transcription Initiation Site
In Situ Nick-End Labeling
Meiosis
Gonadotropins
Epigenomics
Spermatozoa

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Reproductive Medicine
  • Endocrinology
  • Urology

Cite this

Shiraishi, K., Shindo, A., Harada, A., Kurumizaka, H., Kimura, H., Ohkawa, Y., & Matsuyama, H. (2018). Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders. Andrology, 6(1), 158-165. https://doi.org/10.1111/andr.12438

Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders. / Shiraishi, K.; Shindo, A.; Harada, A.; Kurumizaka, H.; Kimura, H.; Ohkawa, Y.; Matsuyama, H.

In: Andrology, Vol. 6, No. 1, 01.2018, p. 158-165.

Research output: Contribution to journalArticle

Shiraishi, K, Shindo, A, Harada, A, Kurumizaka, H, Kimura, H, Ohkawa, Y & Matsuyama, H 2018, 'Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders', Andrology, vol. 6, no. 1, pp. 158-165. https://doi.org/10.1111/andr.12438
Shiraishi, K. ; Shindo, A. ; Harada, A. ; Kurumizaka, H. ; Kimura, H. ; Ohkawa, Y. ; Matsuyama, H. / Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders. In: Andrology. 2018 ; Vol. 6, No. 1. pp. 158-165.
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