High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy.
High Dosages of Equine Chorionic Gonadotropin Exert Adverse Effects on the Developmental Competence of IVF-Derived Mouse Embryos and Cause Oxidative Stress-Induced Aneuploidy.
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高剂量的马绒毛膜促性腺激素对体外受精小鼠胚胎的发育能力产生不利影响，并导致氧化应激诱导的非整倍体
DOI：
10.3389/fcell.2020.609290
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发表时间：
2020
影响因子：
5.5
通讯作者：
He P
中科院分区：
文献类型：
--
作者：
Lin E;Li Z;Huang Y;Ru G;He P
促性腺激素在调节女性生殖能力和生育能力方面发挥着重要作用。本研究旨在探讨增加马绒毛膜促性腺激素(ECG；又称孕马血清促性腺激素，PMSG)诱导超数排卵对小鼠胚胎发育能力和体外受精(IVF)中非整倍体形成的影响。心电图呈剂量依赖性地提高每只小鼠的卵母细胞产量。给予15IU的心电显着降低受精率和四细胞胚胎及囊胚的形成，并增加染色体非整倍体的风险。体外受精囊胚中细胞总数、内细胞团(ICM)细胞和滋养外胚层细胞(TE)最少。此外，0、5和10IU心电处理组比15IU心电处理组有更多的胚泡和更少的凋亡细胞。我们还研究了活性氧的水平及其在几个变量中的变化：线粒体膜电位；活跃的线粒体；线粒体超氧化物生产；三磷酸腺苷含量；纺锤体结构；染色体核型；微丝分布；以及极光B[染色体乘客复合体的重要组成部分]、纺锤体组装检查点蛋白有丝分裂停滞缺陷2样1(MAD2L1)和DNA损伤反应蛋白γH2AX的表达。注射15IU的心电可增加ROS水平，迅速降低线粒体数和线粒体超氧化物歧化能力，降低ATP含量，增加异常纺锤体形成率，诱发染色体数目和微丝分布异常，提示高剂量的心电可改变小鼠胚胎的发育能力，对体外受精胚胎产生不利影响。此外，γH_2AX的出现以及Aurora B和MAD2L1表达的显著增加表明，在小鼠体外受精早期胚胎中，给予相对较高剂量的心电可以引起由ROS诱导的DNA损伤触发的Aurora B介导的SAC激活，以自我纠正非整倍体的形成。这些发现提高了我们对促性腺激素应用的认识，为促性腺激素的治疗提供了理论依据。
Gonadotropins play vital roles in the regulation of female reproductive ability and fertility. Our study aimed to determine the effects of superovulation induced by increasing doses of equine chorionic gonadotropin [eCG; also referred to as pregnant mare serum gonadotropin (PMSG)] on the developmental competence of mouse embryos and on aneuploidy formation during in vitro fertilization (IVF). eCG dose-dependently enhanced the oocyte yield from each mouse. Administration of 15 IU eCG significantly reduced the fertilization rate and the formation of four-cell embryos and blastocysts and increased the risk of chromosome aneuploidy. The IVF-derived blastocysts in the 15 IU eCG treatment group had the fewest total cells, inner cell mass (ICM) cells and trophectoderm (TE) cells. Moreover, more blastocysts and fewer apoptotic cells were observed in the 0, 5, and 10 IU eCG treatment groups than in the 15 IU eCG treatment group. We also investigated reactive oxygen species (ROS) levels and variations in several variables: mitochondrial membrane potential (MMP); active mitochondria; mitochondrial superoxide production; adenosine triphosphate (ATP) content; spindle structures; chromosome karyotypes; microfilament distribution; and the expression of Aurora B [an important component of the chromosomal passenger complex (CPC)], the spindle assembly checkpoint (SAC) protein mitotic arrest deficient 2 like 1 (MAD2L1), and the DNA damage response (DDR) protein γH2AX. Injection of 15 IU eCG increased ROS levels, rapidly reduced MMP, increased active mitochondria numbers and mitochondrial superoxide production, reduced ATP content, increased abnormal spindle formation rates, and induced abnormalities in chromosome number and microfilament distribution, suggesting that a high dose of eCG might alter developmental competence and exert negative effects on IVF-obtained mouse embryos. Additionally, the appearance of γH2AX and the significantly increased expression of Aurora B and MAD2L1 suggested that administration of relatively high doses of eCG caused Aurora B-mediated SAC activation triggered by ROS-induced DNA damage in early mouse IVF-derived embryos for self-correction of aneuploidy formation. These findings improve our understanding of the application of gonadotropins and provide a theoretical basis for gonadotropin treatment.
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DOI：
10.1055/s-2007-1016332
发表时间：
1996-08-01
期刊：
SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY
影响因子：
--
作者：
Chegini, N
通讯作者：
Chegini, N
影响因子：
3.6
作者：
Combelles, CMH;Albertini, DF
通讯作者：
Albertini, DF
影响因子：
4
作者：
Bazrgar, Masood;Gourabi, Hamid;Baharvand, Hossein
通讯作者：
Baharvand, Hossein
影响因子：
6.1
作者：
Ertzeid, G;Storeng, R
通讯作者：
Storeng, R
影响因子：
--
作者：
Behringer, Richard;Gertsenstein, Marina;Nagy, Andras
通讯作者：
Nagy, Andras