生物钟基因Bmal1对早期自然流产的影响  

Effects of Circadian Gene Bmal1 on Early Spontaneous Abortion

作　　者：徐丹[1] 王玉霞[1] 左萌 张文倩 XU Dan;WANG Yu-xia;ZUO Meng;ZHANG Wen-qian(Department of Reproductive Medicine,The First Affiliated Hospital,Jinan University,Guangzhou510630,China)

机构地区：[1]暨南大学附属第一医院生殖科,510630

出　　处：《国际生殖健康／计划生育杂志》2018年第4期338-341,共4页Journal of International Reproductive Health/Family Planning

基　　金：2016年广东省自筹经费类科技计划项目(2016ZX0049);2017年广州市科学研究专项项目(2060404)

摘　　要：Bmal1(Brain and muscle arnt-like 1)作为生物钟基因的核心基因之一,在女性生殖系统中均有表达,其昼夜节律性表达参与了发情周期的产生、排卵、着床及妊娠的维持。Bmal1表达改变与流产的发生有关联,可通过多种机制引起妊娠丢失,其表达下调可通过SP1-DNMT1/DAB2IP途径引起基质金属蛋白酶2/9表达降低,从而抑制滋养细胞迁移和侵袭;Bmal1基因缺失干扰了卵巢颗粒细胞类固醇合成相关基因的转录和翻译,从而影响妊娠相关激素的分泌,并通过磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(m TOR)信号通路促进颗粒细胞凋亡;Bmal1表达下降可引起卵巢和输卵管中活性氧增加从而降低卵母细胞受精、早期胚胎发育和着床潜能,最终导致胚胎丢失。本文就生物钟基因Bmal1对早期自然流产的影响进行综述。Brain and muscle arnt-like 1（Bmal1） as one of the core genes of the clock geneis mainly expressed in the female reproductive system. The circadian rhythm of Bmal1 expression is involved in estrous cycle, ovulation, implantation, and the maintenance of pregnancy. The changed expression of Bmal1 is related to spontaneous abortion, possibly by a variety of mechanisms. Down-regulation of Bmal1 expression can decrease the expressions of matrix metalloproteinase 2/9 through SP1-DNMT1/DAB2 IP pathway, which followed by the inhibition of trophoblast migration and invasion. The deletion of Bmal1 gene interferes with the transcription and translation of steroid synthesis-related genes in ovarian granulosa cells, which affects the secretion of pregnancyrelated hormones and promotes the apoptosis of granulosa cells through PI3 K/Akt/m TOR signaling pathway. The decreased expression of Bmal1 gene can cause the increased reactive oxygen species in ovary and fallopian tube,which can reduce oocyte fertilization, early embryo development and implantation potential, and eventually lead to embryo loss. In this article, the influence of Bmal1 on early spontaneous abortion was reviewed.

关 键 词：生物钟 昼夜节律 BMAL1 基因表达 流产 自然 胚胎发育 胚胎植入 

分 类 号：R714.21[医药卫生—妇产科学]