Isobutylparaben Negatively Affects Porcine Oocyte Maturation Through Increasing Oxidative Stress and Cytoskeletal Abnormalities

Abstract

As a member of parabens (PBs), Isobutylparaben (IBP) has a broad-spectrum antimicrobial activity and widely used in personal care products and cosmetics. Recent studies have indicated that usage of IBP poses a potential threat to reproductive health. In this study, we aimed to reveal the effects of acute exposure to IBP on the meiotic maturation of porcine cumulus oocyte complexes. Initial study showed that 200 μM of IBP significantly reduced the rate of the first polar body extrusion with no significant effect on cumulus cell expansion; however, 400 μM of IBP could significantly affect both. Further research revealed that abnormal spindles, misalignment chromosomes, and aberrant distributed actin filaments were detected in IBP-treated oocytes, which indicates that the cytoskeleton architecture of oocyte could be the target of IBP. At the same time, ROS level and apoptosis rate of oocyte were significantly increased by IBP exposure. Moreover, the levels of H3K9me3 and H3K27me3 were significantly induced in oocytes by IBP. Collectively, these results demonstrate that acute exposure to IBP could disrupt porcine oocyte maturation through affecting cytoskeleton, oxidative stress, viability and epigenetic modification. Environ. Mol. Mutagen. 61:433-444, 2020. Fig. 7. Schematic representation of negative effects of IBP on porcine oocytes. Oocyte exposure to IBP during meiotic maturation leads to inhibition of cumulus cell expansion, disruption of cytoskeleton, generation of oxidative stress and apoptosis, and alteration of epigenetic modifications. Environmental and Molecular Mutagenesis.

Effects of methylparaben on in vitro maturation of porcine oocytes

“…We found that at concentrations of 750 and 1000 μ m , MePB altered oocyte cytoplasm, which may compromise the resumption of meiosis II. In this regard, our results are similar to those reported by Meng et al (2020), where they observed that IBP generated oocyte cytoplasm damage, specifically to the cytoskeleton, causing disturbances in actin microfilaments. It is known that PBs can produce different biological effects, such asinhibition in membrane transport and mitochondrial function (Soniet al, 2005).…”

“…Therefore, our study showed that MePB has low cytotoxicity on oocytes at the concentration ranges assayed. According to Meng et al (2020), the number of oocytes with apoptosis increased after IBP exposure; however, in another study, the toxic potential of PBs in hepatocytes was evaluated, and they determined that cytotoxicity is proportional to the size of PBs (Nakagawa & Moldeus, 1998). Therefore, the longer the carbon chain of PBs, the more their effect is exacerbated (Andersen, 2008;Soni et al, 2005).…”

“…Additionally, cumulus cell‐oocyte communication through gap junctions is necessary for meiotic arrest and resumption (Zhou et al, 2016). Studies have shown that cumulus cells are susceptible to toxic agents (Jeong et al, 2020; Meng et al, 2020), because one of their primary functions is to protect oocytes from damage. Cumulus cells surround the oocyte, as they are the first ones to be exposed to several xenotoxic agents (Domínguez et al, 2016).…”

“…At 1‐4 m m , the mixture of MePB, EtPB, PrPB and BuPB exacerbates these effects (Samarasinghe et al, 2018). As far as we know, only Meng et al (2020) and Jeong et al (2020) have evaluated the effect of isobutyl‐paraben (IBP) and BuPB in porcine oocytes , respectively. Pigs are used as experimental models because their physiology, anatomy, biochemistry and endocrine system are similar to those of humans (Petters, 1994).…”

Butylparaben Is Toxic to Porcine Oocyte Maturation and Subsequent Embryonic Development Following In Vitro Fertilization

“…Previous studies reported that parabens negatively affected the female reproductive system by decreasing ovarian weight, follicle development, and pregnant maintenance [22]. Moreover, exposure to isobutylparaben during IVM disrupts oocyte maturation through cytoskeleton, ROS, and epigenetic modifications [23]. As BP has the most potent estrogenic effects among parabens, exposure to BP could be more harmful to the female reproductive system.…”