Effects of Glycine on epigenetic modification and early embryonic development in porcine oocytes exposed to monobutyl phthalate

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2024-08-09 DOI:10.1016/j.reprotox.2024.108684

Ran Teng , Lepeng Gao , Xiaoqing Sun , Enbo Zhang , Yutong Sun , Suo Li

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Abstract

Monobutyl phthalate (MBP) is the primary active metabolite of dibutyl phthalate (DBP), the key plasticizer component. A substantial body of evidence from studies conducted on both animals and humans indicates that MBP exposure could result in harmful impacts on toxicity pathways. In addition, it can seriously affect human and animal reproductive health. In our present study, we showed that exposure to MBP causes abnormal epigenetic modifications in porcine oocytes and failure of early embryonic development. However, glycine (Gly) can protect oocytes and early embryos from damage caused by MBP. Our study indicated a significant decrease in the percentage of porcine oocytes that reached the metaphase II (MII) phase when exposed to MBP. SET-domain-containing 2(SETD2)-mediated H3K36me3 histone methylation was detected, and the results showed that MBP significantly decreased the protein expression of H3K36me3 and SETD2. Moreover, the expression of the DNA break markers γH2AX and the mRNA expression of Asf1a, and Asf1b increased in the MBP group. The detection of DNA methylation marker proteins showed that MBP significantly increased the fluorescence intensity of 5-methylcytosine (5mC). The results from our RT-qPCR analysis demonstrated a significant decrease in the mRNA expression of the DNA methylation-related genes Dnmt1 and Dnmt3a, as well as the embryonic developmental potential-related genes Oct4 and Nanog, in porcine oocytes following exposure to MBP. Additionally, the mRNA expression of p53 significantly increased. Subsequently, the effects of MBP on early embryonic development were examined via parthenogenesis activation (PA) and in vitro fertilization (IVF). Exposure to MBP significantly impacted the development of embryos in both PA and IVF processes. The TUNEL staining data showed that MBP significantly increased embryonic apoptosis. However, Gly can ameliorate MBP-induced defects in oocyte epigenetic modifications and early embryonic development.

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甘氨酸对暴露于邻苯二甲酸单丁酯的猪卵母细胞表观遗传修饰和早期胚胎发育的影响

邻苯二甲酸单丁酯（MBP）是邻苯二甲酸二丁酯（DBP）的主要活性代谢物，是塑化剂的关键成分。对动物和人类进行的大量研究表明，接触邻苯二甲酸单丁酯会对毒性途径产生有害影响。此外，它还会严重影响人类和动物的生殖健康。在本研究中，我们发现暴露于 MBP 会导致猪卵母细胞表观遗传学异常改变和早期胚胎发育失败。然而，甘氨酸（Gly）可以保护卵母细胞和早期胚胎免受 MBP 的损害。我们的研究表明，当暴露于 MBP 时，猪卵母细胞达到移行期 II（MII）阶段的百分比明显下降。我们检测了含 SET 域的 2（SETD2）介导的 H3K36me3 组蛋白甲基化，结果表明 MBP 显著降低了 H3K36me3 和 SETD2 的蛋白表达。此外，DNA断裂标记物γH2AX的表达以及Asf1a和Asf1b的mRNA表达在MBP组有所增加。DNA 甲基化标记蛋白的检测显示，MBP 能显著增加 5-甲基胞嘧啶（5mC）的荧光强度。qPCR 分析结果表明，暴露于 MBP 后，猪卵母细胞中 DNA 甲基化相关基因 Dnmt1 和 Dnmt3a 以及胚胎发育潜能相关基因 Oct4 和 Nanog 的 mRNA 表达量明显下降。此外，p53 的 mRNA 表达也显著增加。随后，通过孤雌生殖激活（PA）和体外受精（IVF）研究了 MBP 对早期胚胎发育的影响。在孤雌生殖激活和体外受精过程中，暴露于 MBP 都会明显影响胚胎的发育。TUNEL 染色数据显示，MBP 明显增加了胚胎凋亡。然而，Gly 可以改善 MBP 诱导的卵母细胞表观遗传修饰和早期胚胎发育缺陷。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.