Suman Pankaj, Malhotra Sudha Saryu, Gupta Satish Kumar
Reproductive Cell Biology Laboratory; National Institute of Immunology; Aruna Asaf Ali Marg; New Delhi, India.
JAKSTAT. 2013 Oct 1;2(4):e25155. doi: 10.4161/jkst.25155. Epub 2013 Jun 27.
Leukemia inhibitory factor (LIF) is a pleiotropic growth factor that regulates several biological functions. This review focuses on the LIF-dependent STAT activation and its impact on modulation of trophoblast functions during embryo implantation. LIF is mainly produced by the maternal endometrium at the time of implantation while its receptors are present both on the endometrium and trophoblasts. It might influence blastocyst attachment through STAT3 activation and expression of integrins. After attachment of the blastocyst, trophoblasts undergo proliferation and differentiation into invasive EVTs and non-invasive STBs. Under in vitro conditions, LIF regulates all these processes through activation of STAT- and MAPK-dependent signaling pathways. The observations that LIF and STAT3 knockout mice are infertile further strengthen the notion about the critical involvement of LIF-mediated signaling during embryo implantation. Hence, a better understanding of LIF-STAT signaling would help in improving fertility as use of LIF in in vitro blastocyst culture improves the implanting ability of blastocyst after IVF.
白血病抑制因子（LIF）是一种调节多种生物学功能的多效性生长因子。本综述聚焦于胚胎植入过程中依赖LIF的信号转导及转录激活蛋白（STAT）激活及其对滋养层细胞功能调节的影响。LIF主要在植入时由母体子宫内膜产生，而其受体在子宫内膜和滋养层细胞上均有表达。它可能通过激活STAT3及整合素的表达来影响囊胚着床。囊胚着床后，滋养层细胞会增殖并分化为侵袭性绒毛外滋养层细胞（EVT）和非侵袭性合体滋养层细胞（STB）。在体外条件下，LIF通过激活依赖于信号转导及转录激活蛋白（STAT）和丝裂原活化蛋白激酶（MAPK）的信号通路来调节所有这些过程。LIF和STAT3基因敲除小鼠不育的观察结果进一步强化了LIF介导的信号在胚胎植入过程中起关键作用的观点。因此，更好地理解LIF-STAT信号通路将有助于提高生育能力，因为在体外囊胚培养中使用LIF可提高体外受精后囊胚的着床能力。
