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PreprintCC BYbioRxiv

Cell-type-specific expression of classical and membrane progesterone receptors at the human maternal-fetal interface

  1. 1Kumamoto University

Abstract

Progesterone is essential for the establishment and maintenance of pregnancy, primarily through the classical nuclear progesterone receptor (PGR). However, progesterone also exerts rapid, non-genomic effects through membrane progesterone receptors, including members of the progestin and adipoQ receptor (PAQR) family, whose cellular distribution and potential roles at the human maternal-fetal interface remain poorly understood. We therefore sought to define the cell-type-specific expression landscape of classical and membrane progesterone receptors during early human pregnancy. We analyzed publicly available single-cell RNA-sequencing datasets of the first-trimester human maternal-fetal interface to characterize the expression of PGR and PAQR family members across trophoblast, immune, stromal, and vascular cell populations. Major expression patterns were examined across independent datasets and further assessed using spatial transcriptomic data. PGR expression was predominantly localized to decidual stromal and perivascular populations, whereas individual PAQR family members showed distinct cellular distributions. PAQR6 was enriched in decidual natural killer cells, PAQR7 was broadly expressed in trophoblast populations, PAQR8 was prominently expressed in fetal stromal and macrophage populations, including Hofbauer cells, and PAQR9 showed prominent enrichment in syncytiotrophoblasts. Selected cell-type-specific patterns were further supported by spatial transcriptomic analysis. These findings provide a cell-type-resolved framework for investigating how distinct progesterone receptor systems mediate progesterone signaling across maternal and fetal cellular compartments during early human placentation.

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BibTeX
@misc{sagara2026celltypespecific,
  title = {{Cell-type-specific expression of classical and membrane progesterone receptors at the human maternal-fetal interface}},
  author = {A. Sagara and R. Shimokawa and Y. Iwagoi and M. Kobayashi and M. Yamaguchi and H. Mogami and F. Osakada and K. Nagaoka and H. Ohno and I. Kimura and E. Kondoh},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.21.752943},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.21.752943v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Cell-type-specific expression of classical and membrane progesterone receptors at the human maternal-fetal interface
AU  - A. Sagara
AU  - R. Shimokawa
AU  - Y. Iwagoi
AU  - M. Kobayashi
AU  - M. Yamaguchi
AU  - H. Mogami
AU  - F. Osakada
AU  - K. Nagaoka
AU  - H. Ohno
AU  - I. Kimura
AU  - E. Kondoh
PY  - 2026
DA  - 2026/09/21
PB  - bioRxiv
DO  - 10.64898/2026.09.21.752943
UR  - https://www.biorxiv.org/content/10.64898/2026.09.21.752943v1
AB  - Progesterone is essential for the establishment and maintenance of pregnancy, primarily through the classical nuclear progesterone receptor (PGR). However, progesterone also exerts rapid, non-genomic effects through membrane progesterone receptors, including members of the progestin and adipoQ receptor (PAQR) family, whose cellular distribution and potential roles at the human maternal-fetal interface remain poorly understood. We therefore sought to define the cell-type-specific expression landscape of classical and membrane progesterone receptors during early human pregnancy. We analyzed publicly available single-cell RNA-sequencing datasets of the first-trimester human maternal-fetal interface to characterize the expression of PGR and PAQR family members across trophoblast, immune, stromal, and vascular cell populations. Major expression patterns were examined across independent datasets and further assessed using spatial transcriptomic data. PGR expression was predominantly localized to decidual stromal and perivascular populations, whereas individual PAQR family members showed distinct cellular distributions. PAQR6 was enriched in decidual natural killer cells, PAQR7 was broadly expressed in trophoblast populations, PAQR8 was prominently expressed in fetal stromal and macrophage populations, including Hofbauer cells, and PAQR9 showed prominent enrichment in syncytiotrophoblasts. Selected cell-type-specific patterns were further supported by spatial transcriptomic analysis. These findings provide a cell-type-resolved framework for investigating how distinct progesterone receptor systems mediate progesterone signaling across maternal and fetal cellular compartments during early human placentation.
ER  -