Researchers in a 2023 study found “massive alterations” in placental gene expression from mouse embryos that were grown using plastic dishes, compared to placentas from mouse embryos that developed in the uterus.
Some studies have shown an increased risk of preeclampsia or low birth weight of babies born after IVF, suggesting that certain aspects of the IVF procedure may play a role in these outcomes.
Most IVF labs culture embryos using plastic dishes, so Kouakou et al. (2023) wanted to see if plastic had any effect on the placenta. They compared placental gene expression from mouse embryos that were cultured in plastic or glass dishes, to placentas that developed in vivo (inside the mouse, by natural pregnancy).
In this study, embryos were collected from in vivo mice, or were generated in vitro after growing on glass or plastic dishes. Embryos of the same developmental stage (non-expanded blastocysts) were then transferred to the uterus of mice. At day 16.5, the mice were sacrificed and the placentas were collected for analysis.
If you’re not clear on basic molecular biology (gene expression), I recommend you check out my Biology 101 post. This post doesn’t count toward the paywall’s limit.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Different genes are turned on/off in plastic- vs glass-derived placentas
Using a microarray, gene expression analysis of the different placental tissue showed that 1,121 genes were expressed differently from plastic-derived placentas compared to in vivo-derived placentas, while only 200 genes were differentially expressed from glass-derived placentas.
When they looked at plastic- vs glass-derived placentas, they found that 434 genes were expressed differently.
Remember, gene expression tells us about what genes are turned on or off. It’s kind of like a “volume control” that dictates how much protein is made. Here they’re looking at what genes are “differentially expressed,” so the number of genes that are on/off in one placenta (plastic-derived) compared to another placenta (glass-derived). They found that there were a high number of genes that were turned on/off from the plastic- vs glass-derived placentas, which tells us that there’s something different about these placentas.
They also compared gene expression in the brains of the fetuses, and found <49 differentially expressed genes. This suggests that tissues besides the placenta, like the brain, don’t show major differences in what genes are on/off.
A separate analysis was done using a different technique called quantitative PCR (qPCR), to measure gene expression of some representative genes they discovered in their microarray analysis from above. They found that these genes were differentially expressed here also, with a high correlation to the microarray data.
Differentially expressed genes in plastic-derived placentas are stress-related
To learn more about the genes that are differentially expressed, the researchers performed a “gene set enrichment analysis.” Here, a computer analyzes the gene expression data to look for sets of genes that share biological pathways or functions.
They found that the differentially expressed genes displayed a “massive over representation” of stress genes (inflammatory, nutrition, hypoxia). Other genes were involved in inflammation, cell division and detoxification.
Conclusions
This study found that mouse embryos grown in plastic dishes had “massive alterations” in placental gene expression compared to placentas from fetuses that developed in vivo.
There were differences with glass also, but about 6 times less. Over 400 genes were differentially expressed in the placentas of fetuses derived from plastic vs glass dishes.
There were “no significant modifications” of the gene expression profile in brain tissue examined. So the differences that plastic induce may be limited to the placenta.
The genes that were differentially regulated were involved in stress responses, inflammation and detoxification.
The authors note that this may be due to stress induced by the plastic itself, or a response to protect vital organs from plastic.
Previous research (reviewed by by Rosenfeld (2021)) has shown that maternal exposure to Bisphenol A (BPA) can alter the expression of specific genes in the placenta, some of which were found in this study, which is “striking since previous literature concerns mainly mother exposure, while our study deals with direct exposure of the developing embryo.”
BPA, or other chemicals, may be present in plastic culture dishes, and even undetectable levels might cause stress to the developing embryo. Furthermore, since the composition of the dishes is proprietary, there may be differences in these chemicals between manufacturers.
This may explain why some studies have found increased risks of placental diseases (like preeclampsia) or low birth weights after IVF.
It’s important to point out that this data is only showing that there’s an increase in the expression of stress-related genes in plastic-derived placentas. It’s not showing that culturing embryos in plastic leads to any type of placental disease, or any adverse neonatal outcomes. Furthermore, this study took place in mice, so it’s unclear if the same effect will be seen in human placentas.
Another issue is that the plastic they used was not IVF-grade. IVF grade materials undergo further testing to ensure suitability for human use, including “mouse embryo assays” to show that mouse embryos can grow properly on the dish. However, they aren’t tested to show differences in gene expression profiles as in this study. Still, there may be a less dramatic difference in using IVF grade dishes compared to standard dishes.
More research is needed to show that embryos cultured with plastic lead to adverse outcomes in humans.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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