Department of Animal Sciences, University of Illinois, 1207 West Gregory Drive, Urbana, Illinois 61801, USA.
Reproduction. 2010 Dec;140(6):911-20. doi: 10.1530/REP-09-0481. Epub 2010 Sep 14.
Extracellular matrix metalloproteinase inducer (EMMPRIN; BSG) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates, endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, BSG and MMPs are expressed in the endometrium of cycling baboons, and their expression is hormonally regulated by ovarian hormones, but endometriosis disrupts this regulation. BSG expression was evaluated in the baboon endometrium by q-PCR and immunohistochemistry. In the endometrium of control cycling animals, BSG mRNA levels were highest in late secretory stage tissue. BSG protein localized to glandular epithelial cells during the proliferative phase; whereas, secretory stage tissues expressed BSG in glandular and luminal epithelia with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with the highest levels found during menstruation. In ovariectomized animals, BSG endometrial mRNA levels were highest with treatment of both estrogen and progesterone than that with only estrogen. Estrogen alone resulted in BSG protein localization primarily in the endometrial glandular epithelia, while estrogen and progesterone treatment displayed BSG protein localization in both the glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared with the control cycling animals. In the eutopic endometrium of endometriotic animals, BSG mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP7 compared with the control animals. In baboons, BSG and MMP endometrial expression is regulated by both ovarian hormones, and their expression patterns are dysregulated in endometriotic animals.
细胞外基质金属蛋白酶诱导因子 (EMMPRIN; BSG) 通过基质金属蛋白酶 (MMPs) 调节组织重塑。在人类和非人类灵长类动物中,子宫内膜重塑对于月经和子宫内膜异位症的发病机制非常重要。我们假设,与人类一样,BSG 和 MMPs 在周期性狒狒的子宫内膜中表达,其表达受卵巢激素的激素调节,但子宫内膜异位症会破坏这种调节。通过 q-PCR 和免疫组织化学评估了狒狒子宫内膜中的 BSG 表达。在对照周期性动物的子宫内膜中,BSG mRNA 水平在晚期分泌期组织中最高。BSG 蛋白在增殖期定位于腺上皮细胞;而在分泌期组织中,BSG 蛋白在腺上皮和腔上皮中表达,基质染色较弱。几种 MMPs 在整个月经周期中差异表达,在月经期间表达水平最高。在去卵巢动物中,与仅用雌激素相比,用雌激素和孕激素处理时子宫内膜 BSG mRNA 水平最高。单独使用雌激素导致 BSG 蛋白主要定位于子宫内膜腺上皮,而雌激素和孕激素处理则显示 BSG 蛋白定位于腺上皮和基质细胞。与对照周期性动物相比,外源性激素处理导致所有 MMPs 的表达模式不同。在子宫内膜异位症动物的在位子宫内膜中,BSG mRNA 水平和蛋白在疾病进展早期升高,但随后降低。与对照动物相比,子宫内膜异位症升高了所有 MMPs 的表达,除 MMP7 外。在狒狒中,BSG 和 MMP 子宫内膜表达受卵巢激素的双重调节,其表达模式在子宫内膜异位症动物中失调。