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Intracellular pH monkey embryos at various stages of organogenesis estimated by dimethadione distribution
M D Collins1, W J Scott, A G Hendrickx
1Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, OH 45229-2899, USA.
Abstract:
Previous experiments using the transplacental distribution of 14C-DMO (5,5-dimethyloxazolidine-2,4-dione or commonly known as dimethadione) have demonstrated that the pH of rat embryos and fluids progressively decreases during organogenesis. The aim of the present experiments was to similarly evaluate pH changes during organogenesis in the cynomolgus monkey, which is a model for human embryogenesis. Using DMO quantitated by gas chromatography-mass spectrometry as opposed to the counting of radiolabelled compound, cynomolgus monkey embryos were determined to undergo a similar decrease in embryonic pHi over an approximately comparable period of development (Days 24-36 of gestation). The ratio of DMO in chorionic fluid to DMO in maternal plasma in the cynomolgus monkey also displayed a decrease with advancing gestational age indicative of a pH decrease. The DMO transplacental distribution was found to be significantly slower in the cynomolgus monkey than that in rodents. The present investigation indicates that the magnitude of the reduction of pH in embryonic cells and in extra-embryonic fluids over a period of organogenesis in the cynomolgus monkey is similar to the reduction detected in rodent embryos and fluids over a comparable developmental period, but the relative gradient between maternal blood pH and embryonic intracellular pH is different. The difference in the pH gradient between the two species may lead to differential transplacental distribution of exogenous and endogenous substances.
Insights
Embryonic pH decreases during organogenesis in cynomolgus monkeys, similar to rats. However, the pH gradient between maternal blood and embryonic cells differs, potentially impacting substance transfer across the placenta.
Area of Science:
- Developmental Biology
- Toxicology
- Reproductive Science
Background:
- Embryonic pH changes during development are critical for normal organogenesis.
- Previous studies in rodents showed a progressive decrease in embryonic pH during organogenesis.
- The cynomolgus monkey serves as a relevant model for human embryogenesis.
Purpose of the Study:
- To evaluate pH changes during organogenesis in cynomolgus monkey embryos.
- To compare embryonic pH dynamics in cynomolgus monkeys with rodent models.
- To investigate the implications of pH gradients on transplacental substance distribution.
Main Methods:
- Utilized 5,5-dimethyloxazolidine-2,4-dione (DMO) to assess embryonic and fluid pH.
- Quantitated DMO levels using gas chromatography-mass spectrometry.
- Analyzed DMO distribution between embryonic tissues, extra-embryonic fluids, and maternal plasma.
Main Results:
- Cynomolgus monkey embryos exhibited a decrease in intracellular pH (pHi) between gestational days 24-36.
- The ratio of DMO in chorionic fluid to maternal plasma decreased with advancing gestation, indicating a pH decline.
- DMO transplacental distribution was slower in cynomolgus monkeys compared to rodents.
- The magnitude of pH reduction was similar to rodents, but the maternal-embryonic pH gradient differed.
Conclusions:
- Embryonic and extra-embryonic fluid pH decreases during organogenesis in cynomolgus monkeys, mirroring rodent models.
- A distinct pH gradient exists between maternal blood and embryonic intracellular pH in cynomolgus monkeys compared to rodents.
- Differences in the pH gradient may influence the transplacental transfer of various substances.