Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice

Hahyun Park, Hee Seo Park, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ochratoxin A (OTA) is a mycotoxin originating from Penicillium and Aspergillus. In addition to toxic effects in various tissues and cells, including neurons, immune cells, hepatocytes, and nephrons, it also causes carcinogenesis and teratogenesis. Although the negative effects of OTA with respect to the pathogenesis of diseases and the malfunction of various organs have been studied widely, the biological signaling mechanisms in testicular cells are less well known. Therefore, we determined the hazardous effect of OTA in two types of testicular cells: TM3 (mouse Leydig cells) and TM4 (mouse Sertoli cells). Treatment with OTA led to a significant decrease in the proliferation of both cell lines, as revealed by an increased proportion of cells in the sub-G1 phase. In addition, the phosphorylation of signaling molecules belonging to the PI3K (Akt, P70S6K, and S6) and MAPK (ERK1/2 and JNK) pathways was regulated by OTA in a dose-dependent manner in TM3 and TM4 cells. Furthermore, the combination treatment of OTA and signaling inhibitors (LY294002, U0126, or SP600125) exerted synergistic antiproliferative effects in TM3 and TM4 cells. OTA also reduced the concentration of calcium ions in the cytosol and mitochondria, which disrupted the calcium homeostasis necessary for maintaining the normal physiological functions of testicular cells. In conclusion, the results of the present study demonstrate the mechanism underlying the antiproliferative effects of OTA in mouse testicular cells. Exposure to OTA may result in abnormal sperm maturation and the failure of spermatogenesis, which leads to male infertility.

Original languageEnglish
Pages (from-to)71-82
Number of pages12
JournalMedical mycology
Volume58
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Fingerprint

Leydig cells
Leydig Cells
Sertoli Cells
Sertoli cells
ochratoxin A
mice
cells
MAP Kinase Signaling System
Sperm Maturation
Teratogenesis
70-kDa Ribosomal Protein S6 Kinases
Calcium
calcium
S 6
nephrons
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mycotoxins
Poisons
Penicillium
Male Infertility

Keywords

  • Ochratoxin A
  • proliferation
  • signaling
  • spermatogenesis
  • testis

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice. / Park, Hahyun; Park, Hee Seo; Lim, Whasun; Song, Gwonhwa.

In: Medical mycology, Vol. 58, No. 1, 01.01.2020, p. 71-82.

Research output: Contribution to journalArticle

Park, Hahyun ; Park, Hee Seo ; Lim, Whasun ; Song, Gwonhwa. / Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice. In: Medical mycology. 2020 ; Vol. 58, No. 1. pp. 71-82.
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