2. Academic Validation
  3. High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells

High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells

  • J Assist Reprod Genet. 2024 Sep 14. doi: 10.1007/s10815-024-03241-3.
Hui Mu # 1 2,  Haikun Yu # 3,  Song Yan 1 2,  Jie Lu 1 2,  Jiaqin Mao 1 2,  Dan Sun 1 2,  Ni Jin 1 2,  Zheng Fang 1 2,  Xueyan Lu 1 2,  Jie Dong 1 2,  Ying Su 1 2,  Shuqiang Chen 1 2,  Xiaohong Wang 4 5
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, No.1 Xinsi Road, Baqiao District, Xi'an, Shaanxi, China.
  • 2 Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an, Shaanxi, China.
  • 3 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Air Force Medical Center, No. 30 Fucheng Road, Haidian District, Beijing, 100142, China.
  • 4 Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, No.1 Xinsi Road, Baqiao District, Xi'an, Shaanxi, China. wangxh919@fmmu.edu.cn.
  • 5 Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an, Shaanxi, China. wangxh919@fmmu.edu.cn.
  • # Contributed equally.
PMID: 39276273 DOI: 10.1007/s10815-024-03241-3
Abstract

Objective: High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood.

Methods: Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels.

Results: The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway.

Conclusion: These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.

Keywords

COH; DSC; E2; IL-11; uNK.

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