PUBLICATION

INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio)

Authors
Assis, L.H., Crespo, D., Morais, R.D., França, L.R., Bogerd, J., Schulz, R.W.
ID
ZDB-PUB-150617-5
Date
2016
Source
Cell and tissue research   363(2): 579-88 (Journal)
Registered Authors
Bogerd, Jan, Schulz, Rüdiger W.
Keywords
INSL3, Spermatogonial differentiation, Androgen release, Gene expression, Adult testis, Zebrafish
MeSH Terms
  • Aging/drug effects
  • Aging/physiology*
  • Androgens/metabolism
  • Animals
  • Bromodeoxyuridine/metabolism
  • Cell Differentiation/drug effects*
  • Cell Proliferation/drug effects
  • Cell Shape/drug effects
  • Follicle Stimulating Hormone/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Humans
  • Insulin/pharmacology*
  • Male
  • Protein Transport/drug effects
  • Proteins/pharmacology*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Sertoli Cells/cytology
  • Sertoli Cells/drug effects
  • Sertoli Cells/metabolism
  • Spermatogonia/cytology*
  • Testis
  • Zebrafish/genetics
  • Zebrafish/growth & development*
PubMed
26077926 Full text @ Cell Tissue Res.
Abstract
INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping