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Updated: May 27, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Low-dose exposure to microplastics retards meiotic maturation via HDAC3 insufficiency
Qi Zhao1,2, Ming Zong1, Entong Song1
1Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Abstract:
Microplastics (MPs) are considered one of the main causes of male and female infertility. However, the reproductive toxicity and its related mechanisms are currently understood primarily through animal models with acute exposure to MPs. In this study, we demonstrate that low-dose exposure to polystyrene microplastics (PSMPs) leads to severely abnormal reproduction in females, manifested by oocyte meiotic maturation defect. Mechanistically, PSMPs exposure induce the overactivation of cell metabolism pathways, insufficient HDACs, and H4K16 hyperacetylation in oocytes both in vivo and in vitro. When an HDAC3 inhibitor is added, the oocyte maturation defect, overactivation of cell metabolism pathways, and H4K16 hyperacetylation are recapitulated. Conversely, the overexpression of HDAC3 can rescue the defects in meiotic maturation induced by PSMPs. Our observations suggest a direct link between the maturation defects caused by PSMPs and HDAC3 insufficiency. Thus, we propose potential treatments to address the meiotic maturation defect of oocytes in women highly exposed to MPs by activating or supplying HDAC3.
Insights
Polystyrene microplastics (PSMPs) cause female infertility by impairing oocyte maturation. This occurs due to insufficient HDAC3, leading to metabolic changes and abnormal histone acetylation, suggesting HDAC3 activation as a potential treatment.
Area of Science:
- Reproductive Toxicology
- Epigenetics
- Environmental Health
Background:
- Microplastics (MPs) are linked to infertility, but mechanisms remain unclear, especially with chronic low-dose exposure.
- Current understanding relies heavily on animal models with acute MP exposure.
- Investigating the impact of environmental contaminants like MPs on reproductive health is crucial.
Purpose of the Study:
- To investigate the effects of low-dose polystyrene microplastics (PSMPs) on female reproductive health.
- To elucidate the underlying molecular mechanisms of PSMP-induced oocyte meiotic maturation defects.
- To identify potential therapeutic targets for MP-related infertility.
Main Methods:
- In vivo and in vitro exposure of oocytes to PSMPs.
- Analysis of oocyte meiotic maturation.
- Assessment of cellular metabolism pathways and histone acetylation (H4K16).
- Pharmacological manipulation using HDAC3 inhibitors and overexpression of HDAC3.
Main Results:
- Low-dose PSMP exposure caused significant female reproductive abnormalities, specifically oocyte meiotic maturation defects.
- PSMP exposure led to overactivated cell metabolism, insufficient HDACs, and H4K16 hyperacetylation in oocytes.
- HDAC3 inhibition recapitulated these defects, while HDAC3 overexpression rescued PSMP-induced maturation defects.
Conclusions:
- PSMP-induced oocyte maturation defects are directly linked to HDAC3 insufficiency.
- HDAC3 plays a critical role in regulating oocyte maturation in response to microplastic exposure.
- Activating or supplementing HDAC3 may offer a therapeutic strategy for women with MP-induced infertility.
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