Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
Biol Reprod. 2018 Jun 1;98(6):752-764. doi: 10.1093/biolre/ioy063.
The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration. Our aim was to compare the proteomic profile of proliferative phase uterine fluid from fertile (n = 9) and idiopathic infertile (n = 10) women. Proteins with ≥2-fold change (P < 0.05) were considered significantly altered between fertile and infertile groups. Immunohistochemistry examined the endometrial localization of identified proteins. Western immunoblotting defined the forms of extracellular matrix protein 1 (ECM1) in uterine lavage fluid. Proteomic analysis identified four proteins significantly downregulated in infertile women compared to fertile women, including secreted frizzled-related protein 4 (SFRP4), CD44, and ECM1: two proteins were upregulated. Seven proteins were unique to the fertile group and six (including isoaspartyl peptidase/L-asparaginase [ASRGL1]) were unique to the infertile group. Identified proteins were classified into biological processes of tissue regeneration and regulatory processes. ASRGL1, SFRP4, and ECM1 localized to glandular epithelium and stroma, cluster of differentiation 44 (CD44) to stroma and immune cells. ECM1 was present in two main molecular weight forms in uterine fluid. Our results indicate a disturbance in endometrial development during the proliferative phase among infertile women, providing insights into human endometrial development and potential therapeutic targets for infertility.
女性月经周期的再生和增殖期是一个关键时期，为随后的接受性分泌期奠定基础。尽管子宫内膜腺及其分泌物对于胚胎着床和存活至关重要，但增殖期，即这些腺形成的时期，很少被研究。我们假设，特发性不孕女性子宫内膜分泌组的改变反映了增殖期子宫内膜再生的紊乱。我们的目的是比较生育能力正常（n=9）和特发性不孕（n=10）女性的增殖期子宫液的蛋白质组谱。具有≥2 倍变化（P<0.05）的蛋白质被认为在生育能力正常和不孕组之间有明显改变。免疫组织化学检查了鉴定蛋白在内膜中的定位。Western 免疫印迹法定义了子宫灌洗液中外细胞基质蛋白 1（ECM1）的形式。蛋白质组学分析鉴定出 4 种在不孕女性中明显低于生育能力正常女性的蛋白质，包括分泌卷曲相关蛋白 4（SFRP4）、CD44 和 ECM1：两种蛋白质上调。7 种蛋白质是生育能力正常组特有的，6 种蛋白质（包括异天冬氨酸肽酶/L-天冬酰胺酶[ASRGL1]）是不孕组特有的。鉴定出的蛋白质被分类为组织再生和调节过程的生物学过程。ASRGL1、SFRP4 和 ECM1 定位于腺上皮和基质，CD44 定位于基质和免疫细胞。ECM1 在子宫液中有两种主要的分子量形式。我们的结果表明，不孕女性在增殖期子宫内膜发育紊乱，为人类子宫内膜发育提供了新的见解，并为不孕提供了潜在的治疗靶点。
