Dai Bojie, Cao Yujing, Liu Weimin, Li Sumin, Yang Yongjun, Chen Dayuan, Duan Enkui
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Endocrine. 2003 Jul;21(2):123-32. doi: 10.1385/ENDO:21:2:123.
Progesterone (P4) is essential for the development of endometrial receptivity for blastocyst implantation and pregnancy maintenance. Many studies have demonstrated that P4 restrains endometrial tissue breakdown by inhibiting the stimulation of matrix metalloproteinases (MMPs), which implies that P4 impedes the invasion of trophoblast cells into endometrial tissue. To investigate the role of P4 on the attachment and invasion of the trophoblast cells in the entire process of embryo implantation, we used two in vitro coculture systems of blastocysts on a monolayer of uterine epithelial cells and ectoplacental cone (EPC) on uterine decidual cells. The results indicated that all doses of P4 significantly promoted blastocyst attachment, and that except for a concentration of 3.18 x 10-8 mol/L, P4 markedly increased the percentage of blastocysts with outgrowth. However, all concentrations of RU486 clearly prevented blastocyst attachment, and except for a concentration of 10-8 mol/L, all doses of RU486 significantly inhibited the outgrowth of blastocysts. The effect of 3.18 x 10-6 mol/L of P4 on the attachment and outgrowth of blastocysts was significantly blocked by all concentrations of RU486. All concentrations of P4 retarded the attachment of EPC on uterine decidual cells and decreased the outgrowth area of EPC. Except for a concentration of 3.18 x 10-8 mol/L, all concentrations of P4 had a significant inhibitory effect on the percentage of EPC outgrowth. Conversely, except for a concentration of 10-8 mol/L, all doses of RU486 had a significant stimulatory effect on the attachment of EPC. All concentrations of RU486 clearly promoted the outgrowth and outgrowth area of EPC. The inhibitory effect of P4 on EPC was clearly blocked by all doses of RU486. In addition, P4 promoted the activity of MMP-2 on blastocysts and EPC, but P4 inhibited the activity of MMP-9 on EPC. In summary, P4 played dual roles at the early and late stages of embryo implantation in mouse. When blastocysts interacted with the uterine epithelial cells, P4 promoted the attachment and invasion of the primary trophoblast giant cells. When EPC was in contact with uterine decidual cells, P4 inhibited the attachment and invasion of the secondary trophoblast giant cells. Furthermore, the role of P4 was transduced through the classic nuclear receptor.
孕酮（P4）对于子宫内膜接受胚泡着床及维持妊娠的发育至关重要。许多研究表明，P4通过抑制基质金属蛋白酶（MMPs）的刺激来抑制子宫内膜组织分解，这意味着P4阻碍滋养层细胞侵入子宫内膜组织。为了研究P4在胚胎着床全过程中对滋养层细胞黏附和侵入的作用，我们使用了胚泡与单层子宫上皮细胞共培养以及外胎盘锥（EPC）与子宫蜕膜细胞共培养这两种体外共培养系统。结果表明，所有剂量的P4均显著促进胚泡黏附，并且除了3.18×10⁻⁸ mol/L的浓度外，P4显著增加了有突出物的胚泡百分比。然而，所有浓度的RU486均明显阻止胚泡黏附，并且除了10⁻⁸ mol/L的浓度外，所有剂量的RU486均显著抑制胚泡突出物的生长。3.18×10⁻⁶ mol/L的P4对胚泡黏附和突出物生长的作用被所有浓度的RU486显著阻断。所有浓度的P4均延迟EPC在子宫蜕膜细胞上的黏附并减小EPC突出物的面积。除了3.18×10⁻⁸ mol/L的浓度外，所有浓度的P4对EPC突出物百分比均有显著抑制作用。相反，除了10⁻⁸ mol/L的剂量外，所有剂量的RU486对EPC的黏附均有显著刺激作用。所有浓度的RU486均明显促进EPC的突出物生长及突出物面积。P4对EPC的抑制作用被所有剂量的RU486明显阻断。此外，P4促进胚泡和EPC上MMP-2的活性，但P4抑制EPC上MMP-9的活性。总之，P4在小鼠胚胎着床的早期和晚期发挥双重作用。当胚泡与子宫上皮细胞相互作用时，P4促进初级滋养层巨细胞的黏附和侵入。当EPC与子宫蜕膜细胞接触时，P4抑制次级滋养层巨细胞的黏附和侵入。此外，P4的作用是通过经典核受体传导的。
