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<p>The human uterine tube serves not only as an organ for gamete transportation and fertilization but also provides a suitable microenvironment for early embryonic development. Mentioned events could not function without the activity of uterine tube epithelial cells (UTECs) and stromal cells, which respond to ovarian estrogen and progesterone. In our experiment, we modeled steroid hormone concentration dynamics as they progress towards the so-called window of implantation (WOI) using human UTEC monolayer cultures and hormonal cell treatment (estrogen and progesterone). Subsequently, human UTECs underwent Quantitative Real-Time PCR (qPCR), and their secretome content was also analyzed using multiplex immunoaffinity analysis on the Luminex MAGPIX<sup>®</sup> platform. Our results highlight the immunomodulatory, angiogenic, and tissue-remodeling factors of UTEC in response to dynamic hormonal changes, as observed from the peri-ovulatory phase through the WOI. The main time points have been the hormonal switch at the beginning of Day 3 and the end of Day 7. The physiological hormonal transition induced a distinct temporal response, marked by early activation of remodeling and angiogenic pathways (BMP4, SPP1, VEGFA, TGIF2) followed by their stabilization, while immune-related genes displayed progressive activation, particularly between Days 3 and 7. Notably, the experimental cultures exhibited the strongest induction of CXCL8, IL-1B, and IL-16 compared with both control conditions, indicating the establishment of a controlled immunomodulatory environment. Similarly, MAGPIX results corroborated the findings, with elevated IL-11 and TNF-B on Day 7. This phenomenon corresponds to the “inflammatory paradox” that typically occurs during embryo implantation, accompanied by the production of angiogenic and tissue remodeling factors such as VEGFA, BMP4, SPP1, TGIF2, and MMPs. These results demonstrate, in a human in vitro cell model, the clinical importance of a stable uterine tube microenvironment for the onset and maintenance of the early stages of physiological gestation, and provide unique insights into the molecular peculiarities of the uterine tube during this period.</p>

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Estrogen and Progesterone-Induced Changes in the Secretory Profile of Human Uterine Tube Epithelial Cells: A Critical Factor of Human Reproduction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月11日

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  • Zuzana Varchulová Nováková,
  • Martin Klein,
  • Soňa Bernátová,
  • Hana Kováčová-Ilijew,
  • Martin Valent,
  • Ľuboš Danišovič,
  • Ivan Varga,
  • Mária Kleinová

摘要

The human uterine tube serves not only as an organ for gamete transportation and fertilization but also provides a suitable microenvironment for early embryonic development. Mentioned events could not function without the activity of uterine tube epithelial cells (UTECs) and stromal cells, which respond to ovarian estrogen and progesterone. In our experiment, we modeled steroid hormone concentration dynamics as they progress towards the so-called window of implantation (WOI) using human UTEC monolayer cultures and hormonal cell treatment (estrogen and progesterone). Subsequently, human UTECs underwent Quantitative Real-Time PCR (qPCR), and their secretome content was also analyzed using multiplex immunoaffinity analysis on the Luminex MAGPIX® platform. Our results highlight the immunomodulatory, angiogenic, and tissue-remodeling factors of UTEC in response to dynamic hormonal changes, as observed from the peri-ovulatory phase through the WOI. The main time points have been the hormonal switch at the beginning of Day 3 and the end of Day 7. The physiological hormonal transition induced a distinct temporal response, marked by early activation of remodeling and angiogenic pathways (BMP4, SPP1, VEGFA, TGIF2) followed by their stabilization, while immune-related genes displayed progressive activation, particularly between Days 3 and 7. Notably, the experimental cultures exhibited the strongest induction of CXCL8, IL-1B, and IL-16 compared with both control conditions, indicating the establishment of a controlled immunomodulatory environment. Similarly, MAGPIX results corroborated the findings, with elevated IL-11 and TNF-B on Day 7. This phenomenon corresponds to the “inflammatory paradox” that typically occurs during embryo implantation, accompanied by the production of angiogenic and tissue remodeling factors such as VEGFA, BMP4, SPP1, TGIF2, and MMPs. These results demonstrate, in a human in vitro cell model, the clinical importance of a stable uterine tube microenvironment for the onset and maintenance of the early stages of physiological gestation, and provide unique insights into the molecular peculiarities of the uterine tube during this period.