In a trending new study, researchers investigated a common chemical and its multigenerational effects on fertility and ovarian function.
Acrylamide
Frying, roasting or baking starchy food at high temperatures produces a Maillard reaction. A problematic result of this reaction is the formation of a chemical compound called acrylamide (ACR). Acrylamide can be found in many common foods, including french fries, chips, bread, crackers, coffee, and so on. Exposure to this chemical during pregnancy has been linked to reduced development and reproductive function.
“Based on the formation of ACR in food during high temperatures and its presence in water and cosmetics [25, 26], this potential EDC may constitute a major problem for human health and could notably affect female fertility by influencing the ovary structure and function.”
While the effects of ACR in-utero have been documented, researchers Nouf Aldawood, Maroua Jalouli, Abdulkarem Alrezaki, Saber Nahdi, Abdullah Alamri, Mohamed Alanazi, Salim Manoharadas, Saleh Alwasel, and Abdel Halim Harrath from King Saud University wondered how exposure to acrylamide impacts health, development and fertility after a second generation. In a new study, the team investigated exposure to this toxin and its effects on ovarian function over the course of two generations of rats. On September 6, 2022, their research paper was published in Aging’s Volume 14, Issue 17, and entitled, “Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging.”
The Study
“In our current study, the focus was on the effect of ACR during pregnancy on the ovarian function extended over two successive generations as the ovaries are considered one of the most sensitive organs to toxic substances and exposure during the fetal stage.”
The researchers raised 20 healthy female Wistar-Albino rats and mated them. Between gestation days six and 21 (delivery), five pregnant rats were dosed daily with distilled water (the control group; no ACR), five pregnant study rats were dosed daily with 2.5 mg/kg of ACR, five pregnant study rats were dosed with 10 mg/kg of ACR, and the last five pregnant rats were dosed with 20 mg/kg of ACR. Offspring exposed to ACR, or animals of the first generation (AF1), were collected, as were the offspring of the control group (CF1). Blood samples were collected and ovaries were assessed at four weeks of age. AF1 and CF1 rats were raised until maturity and mated again. All pregnant rats were dosed depending on what/how much their mother received. The AF1 and CF1 rats gave birth to the second generation: the AF2 and CF2 offspring. Again, blood samples were collected and ovaries were assessed at four weeks of age.
Results
The researchers found that the first generation of offspring from the rats dosed with ACR (AF1) had ovaries that weighed significantly more than those in the control group (CF1). Upon histoarchitecture examination of the ovaries, this weight increase may have been caused by ovarian cysts that were identified within the AF1 rats and indicated a disruption in ovarian function. Interestingly, the results were quite different in AF2 rats. The researchers were surprised to find that prenatal ACR exposure in the second generation decreased ovarian weights and increased estradiol levels, CYP19 mRNA levels and CYP19 protein expression in all three study groups. These findings in the AF2 rats indicated early ovarian aging.
“In this study, we found that the first generation reacted differently from the second generation. Indeed, maternal exposure to ACR caused an ovarian disruption in AF1 as evidenced by severe histopathological damage, development of cysts, and high apoptosis in the stroma cells, and decreased plasmatic estradiol levels and its corresponding CYP19 gene and protein expression. However, it has induced early ovarian aging in AF2 characterized by high estradiol and progesterone levels, upregulation of CYP19, and apoptotic cell death in the stroma.”
Conclusion
“Altogether, the present study suggests that the in utero multigenerational exposure to ACR highly reduced fertility and ovarian function in females of the first generation, while it has induced early ovarian aging in females of the second generation.”
This may be the world’s first study to examine the multigenerational impact of ACR exposure on ovarian function and fertility in female rat offspring. This study provides evidence that in-utero exposure to ACR can lead to ovarian dysfunction and accelerated ovarian aging. Ovarian aging is not only a potential barrier to fertility but also a major risk factor for ovarian cancer. Women should take fetal programming into grave consideration when pregnant. Results from this study have important implications for human health and fertility.
“Moreover, this study provides some interesting evidence for the eventual implication of the epigenetic impacts of endocrine disruptors on female reproduction across generations. Future studies, using genome wide DNA methylation approaches for some specific key biomarkers of ovarian development, such as CYP19, are fundamental to determine how prenatal exposure to endocrine disruptors could drive adverse secondary phenotypic effects among the future generations in both humans and animals.”
Click here to read the full research paper published by Aging.
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