Copper transporter 1 (CTR1) expression by mouse testicular germ cells, but not Sertoli cells, is essential for functional spermatogenesis

Rashin Ghaffari, Kristin R. Di Bona, Christopher L. Riley, John H. Richburg

Research output: Contribution to journalArticle

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Abstract

An imbalance in copper (Cu) tissue homeostasis has a degenerative effect on spermatogenesis and male fertility. The high-affinity Cu transporter 1 (CTR1; SLC31A1) is the major protein responsible for Cu acquisition in eukaryotes and is highly expressed in mouse testes. Studies on yeast and Drosophila have demonstrated the conserved essential function of Cu and CTR1 for meiosis and fertility, implying that CTR1 may play an essential function in mammalian spermatogenesis. In mice, spermatogenesis takes place within the seminiferous epithelium, where tight junctions between somatic Sertoli cells (SCs) create a specialized microenvironment for the development of meiotic germ cells (GCs) by tightly regulating the free transport of metabolites and ions to reach these cells. Here, it is demonstrated that within the seminiferous epithelium, CTR1 is expressed on the membrane of primary pachytene spermatocytes and SCs. To examine the physiological significance of CTR1 in spermatogenesis, mice with a GC-specific (Ctr1 ΔGC ) and SC-specific (Ctr1 ΔSC ) disruption of the Ctr1 gene were generated. The testis of Ctr1 ΔGC mice exhibits a severe progressive loss of GCs starting at postnatal day (PND) 28 leading to testis hypoplasia by adulthood. No spermatogenic recovery was observed in Ctr1 ΔGC testis beyond PND 41, despite the presence of FOXO-1 expressing undifferentiated spermatogonial cells. However, Ctr1 ΔSC mice displayed functional spermatogenesis and were fertile, even though testicular Cu levels and Cu-dependent cellular activities were significantly reduced. These results reveal, for the first time, the importance of CTR1 expression by GCs for maintaining functional spermatogenesis.

Original languageEnglish (US)
Article numbere0215522
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 2019

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Sertoli Cells
Sertoli cells
Spermatogenesis
spermatogenesis
Germ Cells
transporters
germ cells
copper
Cells
mice
Testis
testes
Seminiferous Epithelium
seminiferous epithelium
Tissue homeostasis
Fertility
pachytene stage
Metabolites
Spermatocytes
tight junctions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Copper transporter 1 (CTR1) expression by mouse testicular germ cells, but not Sertoli cells, is essential for functional spermatogenesis. / Ghaffari, Rashin; Di Bona, Kristin R.; Riley, Christopher L.; Richburg, John H.

In: PloS one, Vol. 14, No. 4, e0215522, 04.2019.

Research output: Contribution to journalArticle

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