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JNK/STAT signalling pathway is involved in fluoride-induced follicular developmental dysplasia in female mice

Wen-Peng Zhao1, Hong-Wei Wang1, Jing Liu1

  • 1College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, PR China.

Chemosphere
|June 19, 2018
PubMed

Insights

Excessive fluoride intake damages ovarian granulosa cells, impairing follicular development. This study reveals fluoride-induced apoptosis and altered cell signaling pathways, contributing to reproductive health issues.

Area of Science:

  • Reproductive Biology
  • Toxicology
  • Cell Biology

Background:

  • Previous research linked excessive fluoride (F) to decreased oocyte development via oxidative stress and apoptosis.
  • Understanding the precise mechanisms of F-induced follicular dysplasia is crucial for reproductive health.

Purpose of the Study:

  • To investigate the underlying molecular mechanisms of fluoride-induced follicular dysplasia in female mice.
  • To analyze the impact of excessive fluoride on ovarian granulosa cell structure, proliferation, and apoptosis.

Main Methods:

  • Pathomorphological analysis of ovary tissues using light and transmission electron microscopy.
  • Assessment of DNA damage and granulosa cell proliferation via TUNEL staining and BrdU measurement.
  • Quantification of protein expression for JNK, STAT3, STAT5, CDK2, CDK4, PCNA, and Ki67 using immunohistochemistry and Western blot.

Main Results:

  • Excessive fluoride exposure caused significant structural damage to granulosa cells, including endoplasmic reticulum swelling and mitochondrial vacuolation.
  • Fluoride treatment enhanced granulosa cell apoptosis and inhibited proliferation, leading to a reduced number of granulosa cells around oocytes.
  • Altered expression of key signaling proteins (JNK, STAT3, STAT5, CDK2, CDK4, Ki67) was observed, implicating the JNK/STAT pathway in fluoride-induced follicular dysplasia.

Conclusions:

  • Excessive fluoride exposure induces significant pathological changes in ovarian granulosa cells.
  • The JNK/STAT signaling pathway plays a critical role in the pathogenesis of fluoride-induced follicular dysplasia.
  • These findings highlight the detrimental effects of fluoride on female reproductive health and warrant further investigation.
Keywords:
FluorideFollicleGranulosa cellsJNK/STATProliferation

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