Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
Mol Reprod Dev. 2013 Jan;80(1):59-69. doi: 10.1002/mrd.22137. Epub 2012 Dec 27.
Uterine decidualization, characterized by stromal cell proliferation and differentiation into polyploid decidual cells, is critical to the establishment of pregnancy in mice, although the mechanism underlying this process remains poorly understood. This study is the first to investigate the expression of gamma-amino butyric acid (GABA) and the GABA A-type receptor π subunit (GABPR) in the early-pregnancy mouse uterus and their roles in decidualization. The expression of GABRP was detected from Day 4 to 8 of pregnancy. The effects of GABA and GABA A-type receptor on cell proliferation and apoptosis were investigated using the Cell Titer 96® AQueous One Solution Cell Proliferation Assay and flow cytometry. The levels of cyclin D3 protein were measured in cultured stromal cells artificially induced to undergo decidualization, and treated with GABA and a GABA A-type receptor agonist or antagonist, respectively, at the same time. mRNA expression of gabrp in implantation sites was lower than that in inter-implanted sites. GABA and GABRP protein were localized in the luminal and glandular epithelium, stromal cells, and decidual cells. In vitro, GABPR protein level was decreased in cultured stromal cells during the decidualization process. The addition of GABA and the GABA A-type receptor agonist Muscimol inhibited stromal cell proliferation, promoted apoptosis, and arrested cells in S-phase, followed by decreased expression of cyclin D3. These results show that in mice, GABA was actively involved in inhibiting stromal cell proliferation and suppresses decidualization progress through GABA A-type receptors by down-regulating cyclin D3 level.
子宫蜕膜化，其特征为基质细胞增殖并分化为多倍体蜕膜细胞，这对小鼠妊娠的建立至关重要，尽管这一过程的机制仍知之甚少。本研究首次研究了γ-氨基丁酸（GABA）和 GABA A 型受体 π 亚基（GABPR）在妊娠早期小鼠子宫中的表达及其在蜕膜化中的作用。检测了从妊娠第 4 天到第 8 天 GABRP 的表达。使用 Cell Titer 96® AQueous One Solution Cell Proliferation Assay 和流式细胞术研究了 GABA 和 GABA A 型受体对细胞增殖和细胞凋亡的影响。在人工诱导蜕膜化的基质细胞中测量 cyclin D3 蛋白的水平，并同时用 GABA 和 GABA A 型受体激动剂或拮抗剂处理。植入部位的 gabrp mRNA 表达低于植入部位之间的表达。GABA 和 GABRP 蛋白定位于腔上皮和腺上皮、基质细胞和蜕膜细胞。在体外，培养的基质细胞在蜕膜化过程中 GABPR 蛋白水平降低。添加 GABA 和 GABA A 型受体激动剂 Muscimol 抑制基质细胞增殖，促进细胞凋亡，并将细胞阻滞在 S 期，随后 cyclin D3 的表达下降。这些结果表明，在小鼠中，GABA 通过下调 cyclin D3 水平通过 GABA A 型受体积极参与抑制基质细胞增殖并抑制蜕膜化进程。
