Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging

Abstract

In this study we investigated the effects of multigenerational exposures to acrylamide (ACR) on ovarian function. Fifty-day-old Wistar albino female rats were divided into the control and ACR-treated groups (2.5, 10, and 20 mg/kg/day) from day 6 of pregnancy until delivery. The obtained females of the first (AF1) and second generation (AF2) were euthanized at 4 weeks of age, and plasma and ovary samples were collected. We found that in utero multigenerational exposure to ACR reduced fertility and ovarian function in AF1 through inducing histopathological changes as evidenced by the appearance of cysts and degenerating follicles, oocyte vacuolization, and pyknosis in granulosa cells. TMR red positive cells confirmed by TUNEL assay were mostly detected in the stroma of the treated groups. Estradiol and IGF-1 concentrations significantly decreased as a result of decreased CYP19 gene and its protein expression. However, ACR exposure in AF2 led to early ovarian aging as evidenced by high estradiol and progesterone levels among all treated groups compared to control group, corresponding to the upregulation of the CYP19 gene and protein expression. The apoptotic cells of the stroma were greatly detected compared to that in the control group, whereas no significant difference was reported in ESR1 and ESR2 gene expression. This study confirms the developmental adverse effects of ACR on ovarian function and fertility in at least two consecutive generations. It emphasizes the need for more effective strategies during pregnancy, such as eating healthy foods and avoiding consumption of ACR-rich products, including fried foods and coffee.

Early-Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery

“…In fact, there was a significant increase in ovary weight at the higher doses for both the first and second generations compared to the control group. This finding is in agreement with previous reports showing that treatment with some substances, such as acrylamide, sodium fluoride, BPA, and nonylphenol, led to an increase in ovary weight [ 39 , 40 , 41 , 42 ]. Although cyclic fluctuations are connected to ovarian function during the estrous cycle, it is known that ovarian weight does not significantly change in normal rats.…”

The Effects of Vitamin C on Histological Changes Induced by Acrylamide on Rat Ovary

“…In line with our study, in a study, female rats were exposed to different doses of ACR, found that ACR causes a significant decrease in ovarian weight. This study also stated the possible reproductive toxic effects of ACR in female mice[19]. Petersson and colleagues stated the following effects of a diet containing ACR.…”

“…V refers to the volume component, t is the section thickness, a (p) is the area of one point (1000 μ), ΣP is the total number of points counted in the component, and M is the linear magnification [19]. The total number of primordial, primary, secondary Graafian, and atresian follicles was estimated using the physical dissector counting method.…”

Detection and Quantification of Acrylamide in Second Trimester Amniotic Fluid Using a Novel LC-MS/MS Technique to Determine Whether High Acrylamide Content during Pregnancy Is Associated with Fetal Growth

“…Acrylamide and its metabolites are also known to form adducts with proteins and DNA, raising concerns for genotoxicity [14]. Moreover, evidence of the adverse developmental effects of acrylamides on ovarian function and fertility spanning at least two consecutive generations underlines the necessity for more targeted strategies during pregnancy, including following a healthy diet and eliminating consumption of acrylamide-rich products [15].…”