Arici A, Oral E, Bahtiyar O, Engin O, Seli E, Jones E E
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Hum Reprod. 1997 Jun;12(6):1233-9. doi: 10.1093/humrep/12.6.1233.
Leukaemia inhibitory factor (LIF) is a 43 kDa glycoprotein with a remarkable range of biological actions in different tissue systems. LIF improves the rate of fertilization of mouse oocytes in vitro and up-regulates aromatase enzyme. We postulated that LIF may be an important modulator of ovarian function and may also improve embryo quality in humans. Follicular fluid samples from patients undergoing in-vitro fertilization (IVF) and embryo transfer (n = 123), from women undergoing ovarian stimulation (n = 4) and from women undergoing laparoscopy for tubal ligation during their follicular phase (n = 3) were used. Follicular fluid LIF, oestradiol, and progesterone were measured and embryo quality was assessed. Granulosa-lutein cells were cultured for 3 days in Ham's F-12:Dulbecco's modified Eagle's medium (DMEM). Ovarian stromal cells, isolated by enzymatic dispersion of ovarian tissue, were also cultured in the same medium. Following experimental treatments, LIF mRNA and protein concentrations were quantified. The concentration of LIF was 0.8 +/- 0.3 (mean +/- SEM) pg/ml in pre-human chorionic gonadotrophin (HCG) follicular fluid samples and 13.0 +/- 1.1 pg/ml in post-HCG follicular fluid samples (P < 0.05). LIF levels were undetectable in three follicular fluid samples obtained during unstimulated follicular phase. There was a correlation between follicular fluid LIF and follicular fluid oestradiol concentrations (r = 0.36; P = 0.0001) and the number of grade I embryos (r = 0.62; P = 0.01). LIF mRNA and the protein were expressed constitutively but in low amounts in the ovarian stromal cell cultures. The concentrations of LIF mRNA as well as protein were increased by interleukin (IL)-1alpha and tumour necrosis factor alpha (TNF alpha) in a time- and concentration-dependent manner. Purified granulosa-lutein cells expressed low amounts of LIF mRNA and protein which were not significantly increased by IL-1alpha or TNF alpha. Our findings suggest that HCG stimulates the expression of LIF in follicular fluid. Both granulosa-lutein and ovarian stromal cells express the LIF mRNA and produce the protein. Modulation of LIF in these cells may play an important role in the physiology of ovulation and early embryo development.
白血病抑制因子（LIF）是一种43 kDa的糖蛋白，在不同组织系统中具有广泛的生物学作用。LIF可提高小鼠卵母细胞的体外受精率，并上调芳香化酶。我们推测LIF可能是卵巢功能的重要调节因子，也可能改善人类胚胎质量。研究使用了接受体外受精（IVF）和胚胎移植患者（n = 123）、接受卵巢刺激的女性（n = 4）以及卵泡期接受输卵管结扎腹腔镜手术的女性（n = 3）的卵泡液样本。检测卵泡液中的LIF、雌二醇和孕酮水平，并评估胚胎质量。颗粒黄体细胞在Ham's F - 12：杜尔贝科改良伊格尔培养基（DMEM）中培养3天。通过酶解卵巢组织分离出的卵巢基质细胞也在相同培养基中培养。经过实验处理后，对LIF mRNA和蛋白浓度进行定量。在人绒毛膜促性腺激素（HCG）注射前的卵泡液样本中，LIF浓度为0.8±0.3（平均值±标准误）pg/ml，在HCG注射后的卵泡液样本中为13.0±1.1 pg/ml（P < 0.05）。在未受刺激的卵泡期获得的三个卵泡液样本中未检测到LIF水平。卵泡液LIF与卵泡液雌二醇浓度之间存在相关性（r = 0.36；P = 0.0001），与I级胚胎数量之间也存在相关性（r = 0.62；P = 0.01）。LIF mRNA和蛋白在卵巢基质细胞培养物中组成性表达，但表达量较低。白细胞介素（IL）-1α和肿瘤坏死因子α（TNFα）可使LIF mRNA和蛋白浓度呈时间和浓度依赖性增加。纯化的颗粒黄体细胞表达少量的LIF mRNA和蛋白，IL-1α或TNFα未使其显著增加。我们的研究结果表明，HCG可刺激卵泡液中LIF的表达。颗粒黄体细胞和卵巢基质细胞均表达LIF mRNA并产生蛋白。这些细胞中LIF的调节可能在排卵和早期胚胎发育的生理过程中起重要作用。
