Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells

Abstract

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

“…In vitro and in vivo experiments proved that enhanced AMPK/PGC-1α signaling pathway activity and PGC-1α expression protect RGCs in the RGC-5 cell line, rat primary RGCs, and rat chronic ocular hypertension models ( Chen S. et al, 2013 ; Zhang et al, 2018 ; Uchida et al, 2019 ). A recent study showed that zinc is essential for PGC-1α transcription and increases antioxidant stress in human primary endometrial stromal cells ( Lu et al, 2020 ). However, more research is needed to elucidate the role of zinc in PGC-1α signaling in neurons and RGCs.…”

The Importance of Natural Antioxidants in Female Reproduction

“…Zinc can stabilize the Zn-finger domain of NF-κB [ 148 ] where it acts as an alternative inhibitor of IKB [ 149 ]. As a transcription regulator of Nrf2, it can upregulate some downstream antioxidants through nuclear translocation and thus respond to damage caused by ROS [ 150 ]. Zinc, together with copper, is a cofactor for one of the most important antioxidant enzymes, Zn-SOD/SOD1 [ 151 ], which has a crucial role in women’s ovulation and menstrual cycles by scavenging ROS [ 152 ].…”

Quality assessment of systematic literature on uterine fibroids: a systematic review

“…Comparing the long and short-terms morbidity of laparoscopic myomectomy (even without LUAO), the study modified the Jadad score to assess the quality of Randomized controlled trials (RCTs) but employed methodologic index for nonrandomized studies to evaluate the quality of observational studies (OSs). symptomatic uterine myomas, two independent researchers in Liu, Lu 16 carried out data selection to perform a comparative study of the clinical outcomes of uterine artery embolization and those of high-intensity focused ultrasound (HIFU) ablation in women with myomas. The study quality was assessed using the "Cochrane Handbook for Systematic Reviews" while the pooled mean difference and relative risks were both calculated at 95% confidence interval for the respective continuous data and dichotomous data.…”