Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
Biol Reprod. 2011 Feb;84(2):255-65. doi: 10.1095/biolreprod.110.086942. Epub 2010 Sep 23.
Lpar3 is upregulated in the preimplantation uterus, and deletion of Lpar3 leads to delayed uterine receptivity in mice. Microarray analysis revealed that there was higher expression of Col3a1 and Col6a3 in the Preimplantation Day 3.5 Lpar3(-/-) uterus compared to Day 3.5 wild-type (WT) uterus. Since extracellular matrix (ECM) remodeling is indispensable during embryo implantation, and dynamic spatiotemporal alteration of specific collagen types is part of this process, this study aimed to characterize the expression of four main uterine collagen types: fibril-forming collagen (COL) I and COL III, basement membrane COL IV, and microfibrillar COL VI in the peri-implantation WT and Lpar3(-/-) uterus. An observed delay of COL III and COL VI clearance in the Lpar3(-/-) uterus may be associated with higher preimplantation expression of Col3a1 and Col6a3. There was also delayed clearance of COL I and delayed deposition of COL IV in the decidual zone in the Lpar3(-/-) uterus. These changes were different from the effects of 17beta-estradiol and progesterone on uterine collagen expression in ovariectomized WT uterus, indicating that the altered collagen expression in Lpar3(-/-) uterus is unlikely to be a result of alterations in ovarian hormones. Decreased expression of several genes encoding matrix-degrading metallo- and serine proteinases was observed in the Lpar3(-/-) uterus. These results demonstrate that pathways downstream of LPA3 are involved in the dynamic remodeling of ECM in the peri-implantation uterus.
Lpar3 在着床前子宫中上调，并且 Lpar3 的缺失导致小鼠子宫接受性延迟。微阵列分析显示，在着床前第 3.5 天 Lpar3(-/-)子宫中，Col3a1 和 Col6a3 的表达更高。由于胚胎着床期间细胞外基质 (ECM) 重塑是必不可少的，并且特定胶原类型的动态时空改变是这个过程的一部分，因此本研究旨在表征四种主要子宫胶原类型在着床前 WT 和 Lpar3(-/-) 子宫中的表达：纤维形成胶原 (COL) I 和 COL III、基底膜 COL IV 和微纤维 COL VI。在 Lpar3(-/-)子宫中观察到 COL III 和 COL VI 的清除延迟，这可能与 Col3a1 和 Col6a3 的早期表达有关。COL I 的清除延迟和 COL IV 在蜕膜区的沉积延迟也发生在 Lpar3(-/-)子宫中。这些变化与卵巢切除 WT 子宫中 17β-雌二醇和孕激素对子宫胶原表达的影响不同，表明 Lpar3(-/-)子宫中胶原表达的改变不太可能是卵巢激素变化的结果。在 Lpar3(-/-)子宫中观察到几种编码基质降解金属和丝氨酸蛋白酶的基因表达降低。这些结果表明，LPA3 下游的途径参与了着床前子宫 ECM 的动态重塑。
