Goldsmith Laura T, Weiss Gerson, Palejwala Smita, Plant Tony M, Wojtczuk Andrea, Lambert W Clark, Ammur Nael, Heller Debra, Skurnick Joan H, Edwards Dean, Cole Donna M
Department of Obstetrics, Gynecology, and Women's Health, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4685-9. doi: 10.1073/pnas.0400776101. Epub 2004 Mar 19.
Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor alpha, but not beta, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.
尽管有文献记载蛋白质激素松弛素在各种哺乳动物繁殖过程中具有重要作用，但松弛素在人类繁殖中的作用却鲜为人知，这主要是因为缺乏针对女性或合适的非人类灵长类动物模型的研究。在此，我们描述了一种早期人类妊娠的非人类灵长类动物模型的建立及其在确定松弛素作用方面的应用。结果表明，松弛素对子宫有显著影响，包括子宫重量明显增加、刺激子宫内膜血管生成以及子宫内膜驻留淋巴细胞数量增加。此外，松弛素可降低子宫内膜基质金属蛋白酶1和3的水平，并增加其内源性抑制剂金属蛋白酶组织抑制剂1的水平，从而维持子宫内膜胶原蛋白含量。松弛素显著抑制子宫内膜雌激素受体α而非β以及孕激素受体亚型A和B的水平。松弛素刺激新血管形成、增加含细胞因子的淋巴细胞数量并维持子宫内膜结缔组织完整性的这些发现，与松弛素在早期妊娠的建立和/或维持中发挥重要作用相一致。
