Related Experiment Video
Updated: Jun 9, 2026
Establishment of an Embryo Implantation Model In Vitro
Published on: June 21, 2024
Lowering pH increases embryonic sensitivity to formate in whole embryo culture
J E Andrews1, M Ebron-McCoy, R J Kavlock
1Developmental Toxicology Division, Health Effects Research Laboratory, USEPA, Research Triangle Park, NC 27711, USA.
Insights
Formate exposure harms mammalian embryo development, with toxicity increasing as culture medium pH decreases. Lower pH significantly amplifies formate
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Formate is a common environmental and industrial chemical.
- Understanding its developmental toxicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the effects of formate exposure on mammalian embryo development.
- To determine if culture medium pH influences formate's in vitro developmental toxicity.
Main Methods:
- Rat whole embryo culture system used for day 9.5 embryos.
- Embryos cultured with varying sodium formate concentrations (0-1.6 mg/ml) at different pH levels (6.00-8.13).
- Assessed developmental parameters including protein concentration, somite number, head length, developmental score, crown-rump length, and yolk-sac diameter.
Main Results:
- Decreasing pH alone negatively impacted embryonic development.
- Formate exposure at 1.6 mg/ml affected multiple parameters across all tested pH levels.
- Formate toxicity increased with decreasing pH, leading to 100% lethality at pH 6.00.
- Lower pH levels potentiated formate-induced embryolethality, dysmorphogenesis, and microcephaly.
Conclusions:
- Formate exposure poses a significant risk to mammalian embryo development.
- The developmental toxicity of formate is pH-dependent, with lower pH exacerbating adverse effects.
- These findings highlight the critical role of pH in modulating chemical teratogenicity.
Abstract:
The effects of formate exposure on mammalian embryo development were investigated using the rat whole embryo culture system as a model. Day 9.5 (presomite) rat embryos were explanted and cultured for 48 hr in rotating bottles containing rat serum with 0, 0.2, 0.4, 0.8, 1.2 or 1.6 mg sodium formate/ml culture medium at pH 8.13, 7.75, 7.00, 6.50 or 6.00 to determine whether the pH of the culture medium affects the in vitro developmental toxicity of formate. Several parameters of embryonic development decreased in the presence of decreasing pH, suggesting that altered pH alone could have a negative impact on embryo development. Exposure to 1.6 mg formate/ml affected protein concentration, somite number (SN), head length (HL), developmental score (DS), crown-rump length (CRL) and yolk-sac diameter of embryos at all pH levels. Formate became more toxic with decreasing pH of the culture media. There was an apparent pH-dependent increase in embryolethality at 1.6 mg formate/ml and 100% lethality at pH 6.00. The 1.2-mg/ml formate concentration affected DS, CR, HL and protein content at the pH 7.75 level whereas 0.8 mg formate/ml resulted in reduced DS, HL, CR, SN and protein content at pH levels of 7.00 and lower. At pH 6.5, embryos that were not exposed to formate were not significantly different from the other control groups except in reduced CR but at this pH, all exposure levels of formate resulted in microcephaly and reduction in embryonic protein as well as reduced CR. These data demonstrate that sensitivity to formate-induced embryo toxicity and dysmorphogenesis in whole embryo culture is increased in the presence of lower pH.
