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Maternal genetic effect on apoptosis of ovarian granulosa cells induced by cadmium

Yi Sun1, Yake Lv1, Yuchen Li1

  • 1Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|May 7, 2022
PubMed

Insights

Maternal cadmium exposure caused ovarian cell apoptosis in offspring. This effect diminished across generations, suggesting a self-repair mechanism involving gene regulation and microRNAs.

Area of Science:

  • Reproductive Toxicology
  • Developmental Biology
  • Epigenetics

Background:

  • Cadmium (Cd) exposure during pregnancy can induce adverse effects in offspring.
  • Maternal exposure to toxicants may lead to intergenerational or transgenerational effects.
  • Ovarian granulosa cells (OGCs) are crucial for ovarian function and can be sensitive to toxic insults.

Purpose of the Study:

  • To investigate the maternal genetic effects of cadmium-induced apoptosis in ovarian granulosa cells (OGCs) across generations.
  • To explore the underlying molecular mechanisms, including DNA methylation and microRNA (miRNA) changes.
  • To assess the self-repair capacity of OGCs following maternal cadmium exposure.

Main Methods:

  • Pregnant Sprague-Dawley rats were exposed to cadmium chloride (CdCl2).
  • Offspring (F1, F2, F3 generations) were assessed for OGC apoptosis, mitochondrial membrane potential, and expression of apoptosis-related genes (bcl-xl, Cle-CASPASE-9/Pro-CASPASE-9).
  • DNA methylation sequencing and miRNA microarrays were performed on F2 and F3 generations.

Main Results:

  • Significant apoptosis was observed in F1 OGCs; apoptotic bodies were absent in F2 and F3.
  • Mitochondrial membrane potential decreased in F2 but not F3.
  • Changes in apoptosis-related gene ratios and specific miRNAs (miR-132-3p, miR-199a-5p, miR-1949) were noted, with gradual normalization across generations.
  • Distinct DNA methylation patterns and altered expression of miRNA maturation-related genes and transcription factors were identified.

Conclusions:

  • Maternal cadmium exposure-induced OGC apoptosis shows significant attenuation and disappearance across generations (intergenerational/transgenerational effect).
  • This phenomenon is linked to the self-repair regulation of apoptosis-related genes.
  • Apoptosis-related miRNA alterations and DNA methylation changes play a role, with transcription factors warranting further investigation.
Keywords:
ApoptosisCadmiumDNAOvarian granulosa cellsmiRNA

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