June 3, 2026
Infertility is a major global public health issue, affecting one in six people worldwide. With long-term grant support from the National Science and Technology Council, a research team led by Chair Professor and President of National Chung Cheng University, Dr. Shaw-Jenq Tsai, has discovered that a tiny structure less than 5 micrometers hidden within the endometrium, known as primary cilia, acts like a cellular “antenna” and represents the ultimate key determining whether an embryo can successfully implant. This landmark research finding was recently published in the “Journal of Biomedical Science”.
The research team found that whether an embryo can successfully implant depends on whether endometrial stromal cells can properly extend antenna-like primary cilia. These cilia contain the EP4 receptor for prostaglandin E2 (PGE2). During the first week after ovulation, a key window for implantation, primary cilia become significantly elongated. Acting like antennas, these cilia help cells sense PGE2 signals in the uterine environment and promote stromal cells to differentiate into decidual cells that support embryo implantation. This process, known as decidualization, is a critical transition in which the uterus prepares a receptive environment ready for the implantation of an embryo.
Endometriosis is a common gynecological disease and is a leading cause for female factor infertility. Approximately 30-50% of women with endometriosis experience infertility; however, how this disease affecting embryo implantation and pregnancy remains a mystery. Professor Tsai has studied the pathological mechanisms underlying endometriosis for more than two decades. His team found that the uterine environment of patients contains significantly elevated levels of transforming growth factor beta 1 (TGF-β1), which suppresses the formation of primary cilia, leading to shorter or fewer cilia. This disruption interferes with the decidualization process, making the uterine environment unsuitable for embryo implantation and preventing successful pregnancy. The first author, postdoctoral fellow Huan-Tzu Hou, explained that after filtering and confirmation through an AI-assisted intelligent analysis system, cilia abnormalities were identified as the cause of reduced endometrial receptivity. Clinical observations also showed that endometrial stromal cells from patients with endometriosis had significantly fewer and shorter primary cilia. Mouse experiments further confirmed that when uterine TGF-β1 levels were increased, primary cilia became shorter and pregnancy rates declined significantly. Conversely, when drugs that inhibit TGF-β1 signaling were used, primary cilia formation was restored, and embryo implantation rates were significantly improved.
The research team further collaborated with the Department of Obstetrics and Gynecology at National Cheng Kung University Hospital to correlate their findings with clinical evidence. Dr. Meng-Hsing Wu, Director of the Division of Reproductive Endocrinology in the Department of Ob/Gyn at National Cheng Kung University Hospital, stated: “Clinical evidence shows that patients with endometriosis have much lower pregnancy rates after embryo transfer compared with endometriosis-free women of the same age. This indicates that endometrial receptivity is one of the most important factors determining whether an embryo can successfully implant and subsequently grow.” By retrospectively analyzing clinical data, the team demonstrated that women who achieved successful pregnancy after embryo transfer had longer and more abundant primary cilia in their endometrial cells. Using cilia length and abundance as predictive markers, the pregnancy rate prediction accuracy exceeded 80%, highlighting primary cilia as a promising biomarker for future infertility diagnosis.
This landmark discovery is the first ever study to reveal the key role of primary cilia in endometrial receptivity. The findings not only solve a critical problem in infertility but also provide new directions for drug development and diagnostic evaluation for infertility. In the future, monitoring the status of these cellular “antennas” may allow physicians to more precisely optimize the uterine environment and offering new hope to many families affected by infertility.
Research Contact:
Shaw-Jenq Tsai
Chair Professor and President
National Chung Cheng University
Tel: +886-5-2720411 ext. 10001
Email: seantsai@ccu.edu.tw
Huan-Tzu Hou
Postdoctoral Fellow
Institute of Physiology
National Cheng Kung University
Tel: +886-6-2353535 ext. 5429
Email: skyrain916828@gmail.com
Media Contact:
Yih-Ru Chen
Program Manager
Department of Life Sciences
National Science and Technology Council
Phone: +886-02-2737-7461
E-mail: cyr202407@nstc.gov.tw