Ovarian Toxicity Induced by Aluminum Chloride: Alteration of Cyp19a1, Pcna, Puma, and Map1lc3b genes Expression

Toxicology. 2022 Jan 30:466:153084. doi: 10.1016/j.tox.2021.153084. Epub 2021 Dec 24.

Abstract

Aluminum (Al) is an abundant metal with wide application in our daily lives including medicine, industry, cosmetics, and packaging. After entrance to the body, aluminum binds to transferrin and reaches different tissues. Al is a metalloestrogen that can lead to oxidative stress (OxS) and endocrine disruption. No detailed study can be found addressing the effect of Al on the ovary and granulosa cells (GCs). In this study, the focus is on the treated ovaries and GCs of NMRI mice exposed to low, middle, and high doses of aluminum chloride (AlCl3) via in vitro and in vivo assays. The steroidogenic, proliferative, apoptotic, and autophagic-related genes were examined. Up-regulated expression of steroidogenic and proliferative genes was detected. The observed apoptotic and autophagic genes had variable expression. Interrupted ovarian structure, disrupted folliculogenesis, presence of Call-Exner bodies, overexpression of steroidogenic gene, and unbalanced apoptosis/autophagy and proliferation resembled features of granulosa cell tumor (GCT).

Keywords: Aluminum chloride; Apoptosis; Autophagy; Granulosa cell tumor; Proliferation; Steroidogenesis.

MeSH terms

  • Aluminum Chloride / toxicity*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Aromatase / metabolism
  • Autophagy / drug effects
  • Female
  • Gene Expression / drug effects*
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Ovary / drug effects*
  • Ovary / metabolism*
  • Ovary / pathology
  • Oxidative Stress
  • Proliferating Cell Nuclear Antigen / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • PUMA protein, mouse
  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Proteins
  • Aluminum Chloride
  • Aromatase
  • Cyp19a1 protein, mouse