Department of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea.
Biol Reprod. 2018 Dec 1;99(6):1137-1148. doi: 10.1093/biolre/ioy147.
Cysteine-X-cysteine (CXC) motif chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor type 4 (CXCR4), are involved in regulating the proliferation, migration, and survival of trophoblast cells and the maternal immune response in humans and mice. The present study examined the expression, regulation, and function of CXCL12 and CXCR4 at the maternal-conceptus interface during pregnancy in pigs. The endometrium expressed CXCL12 and CXCR4 mRNAs with the greatest CXCL12 abundance on Day 15 of pregnancy. CXCL12 protein was localized mainly in endometrial epithelial cells, while CXCR4 protein was localized in subepithelial stromal cells, vascular endothelial cells, and immune cells in blood vessels in the endometrium during the estrous cycle and pregnancy. CXCL12 protein was detected in uterine flushing on Day 15 of pregnancy. The conceptus during early pregnancy and chorioallantoic tissues during mid-to-late pregnancy expressed CXCL12 and CXCR4. Interferon-γ increased the abundance of CXCL12, but not CXCR4 mRNA in endometrial explants. Recombinant CXCL12 (rCXCL12) protein dose-dependently increased migration of cultured porcine trophectoderm cells and peripheral blood mononuclear cells (PBMCs). Furthermore, rCXCL12 caused migration of T cells, but not natural killer cells, in PBMCs. This study revealed that interferon-γ-induced CXCL12 and its receptor, CXCR4, were expressed at the maternal-conceptus interface and increased the migration of trophectoderm cells and T cells at the time of implantation in pigs. These results suggest that CXCL12 may be critical for the establishment of pregnancy by regulating trophoblast migration and T cell recruitment into the endometrium during the implantation period in pigs.
半胱氨酸-X-半胱氨酸（CXC）基序趋化因子配体 12（CXCL12）及其受体 CXC 趋化因子受体 4（CXCR4）参与调节人及鼠类滋养层细胞的增殖、迁移和存活以及母体免疫反应。本研究在猪中检查了妊娠期间母体-胚胎界面处 CXCL12 和 CXCR4 的表达、调节和功能。子宫内膜在妊娠第 15 天表达 CXCL12 和 CXCR4 mRNA，其中 CXCL12 丰度最大。在发情周期和妊娠期间的子宫内膜中，CXCL12 蛋白主要定位于子宫内膜上皮细胞，而 CXCR4 蛋白定位于上皮下基质细胞、血管内皮细胞和血管中的免疫细胞。在妊娠第 15 天的子宫冲洗液中检测到 CXCL12 蛋白。在妊娠早期的胚胎和妊娠中期至晚期的绒毛膜-卵黄囊组织中表达 CXCL12 和 CXCR4。干扰素-γ增加了子宫内膜外植体中 CXCL12 的 mRNA 丰度，但不增加 CXCR4 的 mRNA 丰度。重组 CXCL12（rCXCL12）蛋白剂量依赖性地增加培养的猪滋养层细胞和外周血单核细胞（PBMC）的迁移。此外，rCXCL12 引起 PBMC 中 T 细胞的迁移，但不引起自然杀伤细胞的迁移。本研究表明，干扰素-γ诱导的 CXCL12 及其受体 CXCR4 在母体-胚胎界面表达，并在猪着床时增加滋养层细胞和 T 细胞的迁移。这些结果表明，CXCL12 可能通过在猪的着床期调节滋养层细胞迁移和 T 细胞向子宫内膜募集而对妊娠的建立至关重要。
