Currently, many countries and regions worldwide face the challenge of declining population growth due to persistently low rates of female reproduction. Since 2017, China's birth rate has hit historic lows and continued to decline, with the death rate now equaling the birth rate. Concerns have emerged regarding the potential impact of environmental contaminants on reproductive health, including pregnancy loss. Endocrine-disrupting chemicals (EDCs) like phthalate esters (PAEs), bisphenol A (BPA), triclosan (TCS), and perfluoroalkyl substances (PFASs) have raised attention due to their adverse effects on biological systems. While China's 14th Five-Year Plan (2021-2025) for national economic and social development included the treatment of emerging pollutants, including EDCs, there are currently no national appraisal standards or regulatory frameworks for EDCs and their mixtures. Addressing the risk of EDC mixtures is an urgent matter that needs consideration from China's perspective in the near future. In this Perspective, we delve into the link between EDC mixture exposure and pregnancy loss in China. Our focus areas include establishing a comprehensive national plan targeting reproductive-aged women across diverse urban and rural areas, understanding common EDC combinations in women and their surrounding environment, exploring the relationship between EDCs and pregnancy loss via epidemiology, and reconsidering the safety of EDCs, particularly in mixtures and low-dose scenarios. We envision that this study could aid in creating preventive strategies and interventions to alleviate potential risks induced by EDC exposure during pregnancy in China.
Environmental contaminant mixtures present complex toxicological challenges, especially in transgenic organisms where genetic modifications may alter toxicity mechanisms. This study addresses the uncharacterized influence of GFP fusion proteins on mixture interactions using Caenorhabditis elegans. We employed uniform design ray methodology to evaluate 6 compounds, including ionic liquids (ILs) such as 1-butylpyridinium chloride ([bpy]Cl) and 1-butylpyridinium bromide ([bpy]Br), pesticides (dichlorvos and glyphosate), and substituted phenols (4-chlorophenol and 4-nitrophenol), in transgenic DAF-16::GFP (DAF-16) versus wild-type N2 strains. Toxicity interactions were quantified using the improved combination index (CIimp) with 95% observation confidence intervals (OCIs) at 12 h and 24 h. Results showed that while ILs exhibited negligible lethality in N2, they induced marked toxicity in DAF-16. The transgenic strain demonstrated 10-100 times greater lethality to the mixtures compared to N2, with 95% OCIs confirming significant leftward shifts in concentration-response curves. A time-dependent interaction shift occurred: initial antagonism at 12 h (CIimp 1.315-7.340) transitioned to significant synergism exclusively in the DAF-16 strain at 24 h (CIimp <1; 95% OCIs excluded 1). Molecular docking provided a preliminary structural hypothesis, suggesting that GFP fusion might alter the accessibility of potential binding sites on DAF-16. These findings suggest that genetic modifications and exposure duration jointly modulate mixture toxicity, highlighting the need for cautious interpretation when using transgenic models in environmental risk assessment.