2. Academic Validation
  3. Glutamine metabolism promotes human trophoblast cell invasion via COL1A1 mediated by PI3K-AKT pathway

Glutamine metabolism promotes human trophoblast cell invasion via COL1A1 mediated by PI3K-AKT pathway

  • J Reprod Immunol. 2024 Aug 24:166:104321. doi: 10.1016/j.jri.2024.104321.
Jialu Shi 1,  Zhi Lin 1,  Zimeng Zheng 2,  Min Chen 3,  Xu Huang 2,  Jiarui Wang 4,  Mingqing Li 5,  Jun Shao 6
Affiliations

Affiliations

  • 1 Department of Gynecology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200090, China.
  • 2 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China.
  • 3 Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province 310000, China.
  • 4 Shanghai Medical School, Fudan University, Shanghai 200032, China.
  • 5 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200080, China. Electronic address: mqli@fudan.edu.cn.
  • 6 Department of Gynecology, Hospital of Obstetrics and Gynecology, Shanghai Medical School, Fudan University, Shanghai 200090, China. Electronic address: junshao@fudan.edu.cn.
PMID: 39243705 DOI: 10.1016/j.jri.2024.104321
Abstract

Abnormal trophoblast invasion function is an important cause of recurrent spontaneous abortion (RSA). Recent research has revealed a connection between glutamine metabolism and RSA. However, the interplay between these three factors and their related mechanisms remains unclear. To address this issue, we collected villus tissues from 10 healthy women with induced abortion and from 10 women with RSA to detect glutamine metabolism. Then, the trophoblast cell line HTR-8/SVneo was used in vitro to explore the effect of glutamine metabolism on trophoblast cells invasion, which was tested by transwell assay. We found that the concentration of glutamine in the villi of the normal pregnancy group was significantly higher than that in the RSA group. Correspondingly, the expression levels of key Enzymes involved in glutamine synthesis and catabolism, including glutamine synthetase and Glutaminase, were significantly higher in the villi of the normal pregnancy group. Regarding trophoblast cells, glutamine markedly enhanced the proliferative and invasive abilities of HTR-8/SVneo cells. Additionally, collagen type I alpha 1 (COL1A1) was confirmed to be a downstream target of glutamine, and glutamine also activated the PI3K-AKT pathway in HTR-8/SVneo cells. These findings indicate that glutamine metabolism facilitates the invasion of trophoblasts by up-regulating COL1A1 expression through the activation of the PI3K-AKT pathway, but the specific mechanism of COL1A1 requires further study.

Keywords

COL1A1; Glutamine metabolism; PI3K-AKT pathway; Recurrent spontaneous abortion; Trophoblast invasion.

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