Long-term exposure to cadmium disrupts neurodevelopment in mature cerebral organoids.

Cadmium (Cd) is a pervasive environmental pollutant. Increasing evidence suggests that Cd exposure during pregnancy can induce adverse neurodevelopmental outcomes. However, due to the limitations of neural cell and animal models, it is challenging to study the developmental neurotoxicity and underlying toxicity mechanism of long-term exposure to environmental pollutants during human brain development. In this study, chronic Cd exposure was performed in human mature cerebral organoids for 49 or 77 days. Our study found that prolonged exposure to Cd resulted in the inhibition of cerebral organoid growth and the disruption of neural differentiation and cortical layer organization. These potential consequences of chronic Cd exposure may include impaired GFAP expression, a reduction in SOX2+ neuronal progenitor cells, an increase in TUJ1+ immature neurons, as well as an initial increase and a subsequent decrease in both TBR2+ intermediate progenitors and CTIP2+ deep layer cortical neurons. Transcriptomic analyses revealed that long-term exposure to Cd disrupted zinc and copper ion homeostasis through excessive synthesis of metallothionein and disturbed synaptogenesis, as evidenced by inhibited postsynaptic protein. Our study employed mature cerebral organoids to evaluate the developmental neurotoxicity induced by long-term Cd exposure.

An appraisal of current embryo transfer strategies.

Embryo transfer, one of the most essential procedures in assisted reproductive technology, plays a vital role in the success of in-vitro fertilization and intracytoplasmic sperm injection. During the last decades, the strategies for embryo transfer have changed dramatically. In this review, we evaluate the efficacy and safety of several current embryo transfer strategies including fresh versus frozen embryo transfer, cleavage- versus blastocyst-stage embryo transfer, and single- versus double-embryo transfer. Available evidence indicates that the freeze-only strategy improves the live birth rate after the first embryo transfer in high responders while making no difference in normal responders. The risk of ovarian hyperstimulation syndrome is significantly reduced in the freeze-only strategy. Fresh blastocyst-stage embryo transfer increased live birth rate compared to cleavage-stage embryo transfer. The best embryo transfer strategy is one which tailors to individual circumstances and preferences.