Mokhtar Helmy Mohd, Giribabu Nelli, Muniandy Sekaran, Salleh Naguib
Department of Physiology, Faculty of Medicine, University of Malaya 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya 50603 Lembah Pantai, Kuala Lumpur, Malaysia.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):1967-76. eCollection 2014.
Pinopode, a progesterone-dependent endometrial projection which appears during uterine receptivity period, participates in blastocyst implantation. Blastocyst loosely attaches to pinopode via L-selectin ligand (MECA-79). We hypothesized that pinopode and MECA-79 expressions were affected by testosterone. Therefore, the effect of testosterone on pinopode and MECA-79 expressions during uterine receptivity period were investigated.
Ovariectomized adult female rats received 8 days sex-steroid replacement intended to mimic hormonal changes in early pregnancy with day 6 to 8 represents uterine receptivity period. Testosterone (1 mg/kg/day) was injected together with flutamide or finasteride during the period of uterine receptivity. At the end of treatment, rats were sacrificed and uteri were removed. The existence of pinopodes in the endometrium was visualized by electron microscopy and uterine expression and distribution of MECA-79 protein were examined by Western blotting and immunohistochemistry (IHC) respectively.
Abundant pinopodes and MECA-79 expressions were observed in rats received normal steroid replacement regime. Administration of testosterone during uterine receptivity period reduced pinopodes and MECA-79 expressions, which were antagonized by flutamide and not finasteride.
The decrease in uterine pinopodes and MECA-79 expressions during uterine receptivity period by testosterone may cause failure of blastocyst to implant in conditions associated with high level of this hormone.
蜕膜小体是一种在子宫接受期出现的依赖孕酮的子宫内膜突起,参与胚泡着床。胚泡通过L-选择素配体(MECA-79)松散地附着在蜕膜小体上。我们假设蜕膜小体和MECA-79的表达受睾酮影响。因此,研究了睾酮在子宫接受期对蜕膜小体和MECA-79表达的影响。
对成年去卵巢雌性大鼠进行8天的性类固醇替代,旨在模拟妊娠早期的激素变化,第6至8天代表子宫接受期。在子宫接受期,将睾酮(1mg/kg/天)与氟他胺或非那雄胺一起注射。治疗结束时,处死大鼠并取出子宫。通过电子显微镜观察子宫内膜中蜕膜小体的存在情况,分别通过蛋白质印迹法和免疫组织化学(IHC)检测子宫中MECA-79蛋白的表达和分布。
在接受正常类固醇替代方案的大鼠中观察到丰富的蜕膜小体和MECA-79表达。在子宫接受期给予睾酮会降低蜕膜小体和MECA-79的表达,氟他胺可拮抗这种作用,而非那雄胺则不能。
在子宫接受期,睾酮导致子宫蜕膜小体和MECA-79表达降低,这可能会导致在与这种激素水平升高相关的情况下胚泡着床失败。