The University of Tokyo · Immunology and Microbiology
Professor Takehiro Hiraoka's research lab focuses on the molecular and cellular mechanisms underlying uterine function, particularly in endometrial receptivity, embryo implantation, and uterine regeneration. The lab investigates key signaling pathways—especially STAT3—involved in endometrial homeostasis, adenomyosis, and infertility, using innovative mouse models and human tissue analyses. They also develop advanced ex vivo culture systems to model embryo implantation with high fidelity, enabling breakthroughs in understanding early pregnancy establishment. Their work bridges basic reproductive biology with clinical applications in infertility and assisted reproductive technologies.
Figures are computed from collected data and may differ slightly.
Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sit
Although it has been reported that uterine signal transducer and activator of transcription 3 (STAT3) is essential for embryo implantation, the exact roles of uterine epithelial and stromal STAT3 on embryo implantation have not been elucidated. To address this issue, we generated Stat3-floxed/Ltf-iCre (Stat3-eKO), Stat3-floxed/Amhr2-Cre (Stat3-sKO), and Stat3-floxed/Pgr-Cre (Stat3-uKO) mice to delete Stat3 in uterine epithelium, uterine stroma, and whole uterine layers, respectively. We found th
Recurrent implantation failure (RIF) remains a challenging problem in assisted reproductive technology (ART). Further insights into uterine abnormalities that can disturb embryo implantation should be obtained. This review provides an overview of the effects of organic and non-organic uterine disorders on endometrial receptivity. The results suggest that various uterine pathologies can lead to defective embryo implantation via multiple mechanisms. In particular, uterine adenomyosis dysregulates
We found an association between elevated TSH and the decreased rate of clinical pregnancy. This might be related to an ovulatory disorder and pathophysiology of unexplained infertility. These results may reinforce the usefulness of TSH screening in infertility population.
Adenomyosis is a benign uterine disease that causes dysmenorrhea, heavy menstrual bleeding, and infertility; however, its pathophysiology remains unclear. Since signal transducer and activator of transcription 3 (STAT3) is crucial for endometrial regeneration, we hypothesized that STAT3 participates in adenomyosis pathophysiology. To investigate the influence of STAT3 on adenomyosis development, this study was performed using a novel mouse model of adenomyosis and human specimens of eutopic endo
Embryo implantation remains challenging to study because of its inaccessibility in situ despite its essentiality and clinical significance. Although recent studies on long-term culture of authentic and model embryos have provided significant advances in elucidating embryogenesis in vitro, they, without the uterus, cannot genuinely replicate implantation. Here, we have recapitulated bona fide implantation ex vivo at more than 90% efficiency followed by embryogenesis and trophoblast invasion using
Pregnancy comprises multiple stages with complex interactions of molecules and cells, and previous studies have clarified that progesterone (P4) is a key player in pregnancy. Several animal experimental models have been established to address the detailed mechanisms of P4, and genetically engineered mouse models have especially helped us understand its function. P4 receptor (PR)-null female mice show no ovulation, while PR co-chaperone FKBP52-null mice exhibit implantation failure with normal ov
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