Narkar Madhura, Kholkute Sanjeev, Nandedkar Tarala
Cell Biology Department, National Institute for Research in Reproductive Health (ICMR), Parel, Mumbai 400 012, Maharashtra, India.
Theriogenology. 2006 Sep 15;66(5):1194-209. doi: 10.1016/j.theriogenology.2006.03.032. Epub 2006 May 4.
Phase-dependent apoptotic changes in the human endometrium during an ovarian cycle imply a potential role of steroids in the regulation of apoptosis. The present study was undertaken to determine the direct role of hormones in endometrial apoptosis in marmosets (Callithrix jacchus), a primate species which shows similarity to humans in terms of the cycle length and pattern. Endometrial apoptosis was detected by 3'-end labeling (TUNEL) in various phases of ovarian cycle in naturally cycling healthy marmosets (n=14) and also in ovariectomized marmosets (n=13) treated with either estradiol alone (E) or progesterone alone (P) or estradiol followed by progesterone (E+P). Expressions of apoptosis associated genes such as Bcl-2 family members (Bax and Bcl-2), proliferating cell nuclear antigen (PCNA)--a proliferation marker and steroid receptors, ERalpha and PR A were analysed by immunohistochemical methods. Apoptosis was intense in the glandular epithelial cells of endometrium during the mid-luteal phase as compared to other phases in naturally cycling animals; in the E+P group as compared to other groups of ovariectomized animals (P<0.05). Pronounced apoptosis in the mid-luteal phase was accompanied by the increased expression of Bax in glandular epithelial cells; while Bcl-2 immunoreactivity remained unchanged. PCNA expression was higher in the naturally cycling animals in the follicular phase and in the E group of the ovariectomized animals as compared those in the other groups. Immunoreactive ERalpha and PR A in glandular epithelial cells were most abundant during early follicular phase in naturally cycling animals and in both E and E+P groups among the ovariectomized animals. The present study highlights the importance of apoptosis in endometrial remodeling during the ovarian cycle and secondly, the role of both estradiol and progesterone in the regulation of apoptosis.
在卵巢周期中,人类子宫内膜的阶段依赖性凋亡变化表明类固醇在细胞凋亡调节中具有潜在作用。本研究旨在确定激素在狨猴(Callithrix jacchus)子宫内膜凋亡中的直接作用,狨猴是一种在周期长度和模式方面与人类相似的灵长类动物。通过3'-末端标记(TUNEL)检测自然周期健康狨猴(n = 14)以及卵巢切除的狨猴(n = 13)在卵巢周期各阶段的子宫内膜凋亡情况,卵巢切除的狨猴分别单独接受雌二醇(E)或孕酮(P)治疗,或先接受雌二醇治疗后再接受孕酮治疗(E + P)。采用免疫组织化学方法分析凋亡相关基因如Bcl-2家族成员(Bax和Bcl-2)、增殖细胞核抗原(PCNA)——一种增殖标志物以及类固醇受体ERα和PR A的表达。与自然周期动物的其他阶段相比,黄体中期子宫内膜腺上皮细胞中的凋亡较为强烈;与卵巢切除动物的其他组相比,E + P组中的凋亡更为明显(P < 0.05)。黄体中期明显的凋亡伴随着腺上皮细胞中Bax表达的增加;而Bcl-2免疫反应性保持不变。与其他组相比,自然周期动物卵泡期以及卵巢切除动物的E组中PCNA表达较高。自然周期动物卵泡早期以及卵巢切除动物的E组和E + P组中,腺上皮细胞中的免疫反应性ERα和PR A最为丰富。本研究突出了细胞凋亡在卵巢周期中子宫内膜重塑中的重要性,其次,强调了雌二醇和孕酮在细胞凋亡调节中的作用。