Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Department of Animal Science, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla, Sri Lanka.
Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Department of Veterinary Public Health and Pharmacology, Faculty of Veterinary Medicine and Animal Science, The University of Peradeniya, Peradeniya, Sri Lanka.
Reprod Biol. 2021 Jun;21(2):100498. doi: 10.1016/j.repbio.2021.100498. Epub 2021 Mar 4.
Estrogen and progesterone regulate the expression of endometrial proteins that determine endometrial receptivity for embryo implantation. The protein disulfide isomerase (PDI) family of proteins play a diverse role in regulating protein modification and redox function. Although the role of PDIs in cancer progression has been widely studied, their role in endometrial receptivity is largely unknown. We have focused on the expressions of PDIA1, PDIA2, PDIA3, PDIA4, PDIA5, and PDIA6 isoforms in endometrial epithelium under the influence of estrogen and progesterone and investigated their functional role in regulating endometrial receptivity. We found PDIA1-6 transcripts were expressed in endometrial epithelial Ishikawa, RL95-2, AN3CA, and HEC1-B cell lines. The expression of PDIA1 was low and PDIA5 was high in HEC1-B cells, whereas PDIA2 was high in both AN3CA and HEC1-B cells. In Ishikawa cells, estrogen (10 and 100 nM) upregulated PDIA1 and PDIA6, whereas estrogen (100 nM) downregulated PDIA4 and PDIA5; and progesterone (0.1 and 1 μM) downregulated transcript expressions of PDIA1-6. In human endometrial samples, significantly lowered transcript expressions of PDIA2 and PDIA5 were observed in the secretory phase compared with the proliferative phase, whereas no change was observed in the other studied transcripts throughout the cycle. Inhibition of PDI by PDI antibody (5 and 10 μg/mL) and PDI inhibitor bacitracin (1 and 5 mM) significantly increased the attachment of Jeg-3 spheroids onto AN3CA cells. Taken together, our study suggests a role of PDI in regulating endometrial receptivity and the possibility of using PDI inhibitors to enhance endometrial receptivity.
雌激素和孕激素调节子宫内膜蛋白的表达，这些蛋白决定了子宫内膜对胚胎植入的接受能力。蛋白质二硫键异构酶（PDI）家族的蛋白在调节蛋白修饰和氧化还原功能方面发挥着多样化的作用。尽管 PDIs 在癌症进展中的作用已被广泛研究，但它们在子宫内膜接受能力中的作用在很大程度上尚不清楚。我们专注于在雌激素和孕激素的影响下，子宫内膜上皮中 PDIA1、PDIA2、PDIA3、PDIA4、PDIA5 和 PDIA6 同工型的表达，并研究了它们在调节子宫内膜接受能力方面的功能作用。我们发现 PDIA1-6 转录本在子宫内膜上皮 Ishikawa、RL95-2、AN3CA 和 HEC1-B 细胞系中表达。HEC1-B 细胞中 PDIA1 的表达较低，PDIA5 的表达较高，而 AN3CA 和 HEC1-B 细胞中 PDIA2 的表达较高。在 Ishikawa 细胞中，雌激素（10 和 100 nM）上调了 PDIA1 和 PDIA6，而雌激素（100 nM）下调了 PDIA4 和 PDIA5；孕激素（0.1 和 1 μM）下调了 PDIA1-6 的转录表达。在人类子宫内膜样本中，与增殖期相比，分泌期 PDIA2 和 PDIA5 的转录表达明显降低，而在整个周期中，其他研究的转录本没有变化。PDI 抗体（5 和 10 μg/mL）和 PDI 抑制剂 bacitracin（1 和 5 mM）抑制 PDI 的作用显著增加了 Jeg-3 球体附着在 AN3CA 细胞上的数量。综上所述，我们的研究表明 PDI 在调节子宫内膜接受能力中的作用，并有可能使用 PDI 抑制剂来增强子宫内膜接受能力。
