Innervation of the Uterus: An Anatomical Study With Application to Better Understanding Pelvic Pain in Women

Innervation of the Uterus: An Anatomical Study With Application to Better Understanding Pelvic Pain in Women Fabien Robin Department of Digestive Surgery and Liver Transplantation, Rennes University Hospital, Rennes, France Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Search for more papers by this authorMarion Pinsard Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorLéa Roux Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Search for more papers by this authorAudrey Astruc Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Search for more papers by this authorLudivine Dion Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorThomas Bessede Department of Urology, AP-HP, Université Paris-Saclay, Le Kremlin-Bicêtre, France Search for more papers by this authorMartin Bertrand Department of Digestive Surgery, Nîmes University Hospital Center, University of Montpellier, Nîmes, France Search for more papers by this authorPascale Bellaud H2P2 Platform, UMS CNRS 3480–INSERM 018, University of Rennes, Rennes, France Search for more papers by this authorXavier Morandi Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Search for more papers by this authorVincent Lavoué Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorMartha Duraes Department of Gynecological and Breast Surgery, Montpellier University Hospital, Montpellier, France Search for more papers by this authorCorresponding Author Krystel Nyangoh Timoh Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Correspondence: Krystel Nyangoh Timoh ([email protected]) Search for more papers by this authorFabien Robin Department of Digestive Surgery and Liver Transplantation, Rennes University Hospital, Rennes, France Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Search for more papers by this authorMarion Pinsard Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorLéa Roux Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Search for more papers by this authorAudrey Astruc Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Search for more papers by this authorLudivine Dion Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorThomas Bessede Department of Urology, AP-HP, Université Paris-Saclay, Le Kremlin-Bicêtre, France Search for more papers by this authorMartin Bertrand Department of Digestive Surgery, Nîmes University Hospital Center, University of Montpellier, Nîmes, France Search for more papers by this authorPascale Bellaud H2P2 Platform, UMS CNRS 3480–INSERM 018, University of Rennes, Rennes, France Search for more papers by this authorXavier Morandi Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Search for more papers by this authorVincent Lavoué Department of Gynecology, Rennes University Hospital, Rennes, France Search for more papers by this authorMartha Duraes Department of Gynecological and Breast Surgery, Montpellier University Hospital, Montpellier, France Search for more papers by this authorCorresponding Author Krystel Nyangoh Timoh Anatomy Laboratory, Faculty of Medicine, Rennes 1 University, Rennes, France Department of Gynecology, Rennes University Hospital, Rennes, France LTSI UMR, INSERM, Rennes University, Rennes, France Correspondence: Krystel Nyangoh Timoh ([email protected]) Search for more papers by this authorABSTRACT Pelvic pain has a significant impact on quality of life, especially when associated with benign pelvic diseases, such as endometriosis or chronic conditions leading to persistent discomfort. A substantial proportion of women are affected in their reproductive years, making it a public health issue. Even though previous research has provided a map of intrauterine innervation, the origins and pathways of macro-uterine innervation are still poorly understood. A better understanding of the complex network of pelvic nerves is crucial for improving surgical techniques and patient outcomes. We performed immunohistochemistry on pelvic slices of four human fetuses by using a wide variety of neuronal markers. Then, a 3D reconstruction was performed, and the different anatomical structures were identified, as well as the path of the nerve fibers toward the uterus, and nerve specificity was determined. Our findings confirmed that the nerve fibers essential to uterine function and pelvic sensitivity mainly originate from the inferior hypogastric plexus, branching extensively to innervate the uterus, cervix, and surrounding pelvic structures. Two main pathways were identified, one medial and the other anterolateral to the ureter. Considering these pathways during surgical interventions is paramount as their integrity might inadvertently be impacted, leading to postoperative complications, such as pain or functional disorders. The implications of this research extend beyond the operating room, as they will undoubtedly enrich both clinical practice and medical education in the years to come. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. References - Astruc, A., L. Roux, F. Robin, et al. 2024. “Advanced Insights Into Human Uterine Innervation: Implications for Endometriosis and Pelvic Pain.” Journal of Clinical Medicine 13, no. 5: 1433. - Aurore, V., R. Röthlisberger, N. Boemke, et al. 2020. “Anatomy of the Female Pelvic Nerves: A Macroscopic Study of the Hypogastric Plexus and Their Relations and Variations.” Journal of Anatomy 237, no. 3: 487–494. - Bourdon, M., C. Maignien, G. Giraudet, et al. 2024. “Investigating the Medical Journey of Endometriosis-Affected Women: Results From a Cross-Sectional Web-Based Survey (EndoVie) on 1,557 French Women.” Journal of Gynecology Obstetrics and Human Reproduction 53, no. 2: 102708. - Bremer, J., F. Baumann, C. Tiberi, et al. 2010. “Axonal Prion Protein Is Required for Peripheral Myelin Maintenance.” Nature Neuroscience 13, no. 3: 310–318. - Butler-Manuel, S. A., L. D. Buttery, R. P. A'Hern, J. M. Polak, and D. P. Barton. 2002. “Pelvic Nerve Plexus Trauma at Radical and Simple Hysterectomy: A Quantitative Study of Nerve Types in the Uterine Supporting Ligaments.” Journal of the Society for Gynecologic Investigation 9, no. 1: 47–56. - Ceccaroni, M., R. Clarizia, F. Bruni, et al. 2012. “Nerve-Sparing Laparoscopic Eradication of Deep Endometriosis With Segmental Rectal and Parametrial Resection: The Negrar Method. A Single-Center, Prospective, Clinical Trial.” Surgical Endoscopy 26, no. 7: 2029–2045. - Ceccaroni, M., R. Clarizia, and G. Roviglione. 2020. “Nerve-Sparing Surgery for Deep Infiltrating Endometriosis: Laparoscopic Eradication of Deep Infiltrating Endometriosis With Rectal and Parametrial Resection According to the Negrar Method.” Journal of Minimally Invasive Gynecology 27, no. 2: 263–264. - Ceccaroni, M., G. Roviglione, S. Kapurubandara, and G. Ruffo. 2024. “Laparoscopic Eradication of Deep Endometriosis With Segmental Rectosigmoid Resection and Bilateral Posterior Parametrectomy With Nerve-Sparing ‘Touchless’ Technique According to the ‘Negrar Method’.” Journal of Minimally Invasive Gynecology 31, no. 1: 19–20. - Cohen, D. P., S. R. Ikeda, and D. L. Lewis. 1996. “Neuropeptide Y and Calcitonin Gene-Related Peptide Modulate Voltage-Gated Ca2+ Channels in Mature Female Rat Paracervical Ganglion Neurons.” Journal of the Society for Gynecologic Investigation 3, no. 6: 342–349. - Crestani, A., M. Le Gac, É. de Labrouhe, et al. 2024. “Outcomes of Discoid Excision and Segmental Resection for Colorectal Endometriosis: Robotic Versus Conventional Laparoscopy.” Journal of Robotic Surgery 18, no. 1: 87. - Di Tommaso, S., C. Cavallotti, A. Malvasi, et al. 2016. “A Qualitative and Quantitative Study of the Innervation of the Human Non Pregnant Uterus.” Current Protein & Peptide Science 18, no. 2: 140–148. 10.2174/1389203717666160330105341Google Scholar - Ercoli, A., V. Delmas, F. Fanfani, et al. 2005. “Terminologia Anatomica Versus Unofficial Descriptions and Nomenclature of the Fasciae and Ligaments of the Female Pelvis: A Dissection-Based Comparative Study.” American Journal of Obstetrics and Gynecology 193, no. 4: 1565–1573. - Fermaut, M., K. Nyangoh Timoh, C. Lebacle, D. Moszkowicz, G. Benoit, and T. Bessede. 2016. “Identification des sites anatomiques à risque de lésion nerveuse lors de chirurgie pour endométriose pelvienne profonde [Deep Infiltrating Endometriosis Surgical Management and Pelvic Nerves Injury].” Gynécologie, Obstétrique & Fertilité 44, no. 5: 302–308. - Ferrier, C., M. Le Gac, K. Kolanska, et al. 2022. “Comparison of Robot-Assisted and Conventional Laparoscopy for Colorectal Surgery for Endometriosis: A Prospective Cohort Study.” International Journal of Medical Robotics and Computer Assisted Surgery 18, no. 3: e2382. - Gnanamanickam, G. J. E., and I. J. Llewellyn-Smith. 2011. “Innervation of the Rat Uterus at Estrus: A Study in Full-Thickness, Immunoperoxidase-Stained Whole-Mount Preparations.” Journal of Comparative Neurology 519, no. 4: 621–643. - Hern, W. M. 1984. “Correlation of Fetal Age and Measurements Between 10 and 26 Weeks of Gestation.” Obstetrics and Gynecology 63, no. 1: 26–32. - Hollabaugh, R. S., R. R. Dmochowski, and M. S. Steiner. 1997. “Neuroanatomy of the Male Rhabdosphincter.” Urology 49, no. 3: 426–434. - Iwanaga, J., H. J. Kim, K. Akita, et al. 2025. “Ethical Use of Cadaveric Images in Anatomical Textbooks, Atlases, and Journals: A Consensus Response From Authors and Editors.” Clinical Anatomy 38, no. 2: 222–225. - Iwanaga, J., V. Singh, A. Ohtsuka, et al. 2021. “Standardized Statement for the Ethical Use of Human Cadaveric Tissues in Anatomy Research and Education.” Clinical Anatomy 34, no. 1: 2–4. - Kobayashi, M., K. Inoue, E. Warabi, T. Minami, and T. Kodama. 2005. “A Simple Method of Isolating Mouse Aortic Endothelial Cells.” Journal of Atherosclerosis and Thrombosis 12, no. 3: 138–142. - Lemos, N., C. Souza, R. M. Marques, G. Kamergorodsky, E. Schor, and M. J. B. C. Girão. 2015. “Laparoscopic Anatomy of the Autonomic Nerves of the Pelvis and the Concept of Nerve-Sparing Surgery by Direct Visualization of Autonomic Nerve Bundles.” Fertility and Sterility 104, no. 5: e11–e12. - Moszkowicz, D., B. Alsaid, T. Bessede, et al. 2011. “Neural Supply to the Clitoris: Immunohistochemical Study With Three-Dimensional Reconstruction of Cavernous Nerve, Spongious Nerve, and Dorsal Clitoris Nerve in Human Fetus.” Journal of Sexual Medicine 8, no. 4: 1112–1122. - Nyangoh Timoh, K., V. Lavoué, and H. Roman. 2023. “Anatomical Pitfalls of Excision of Deep Endometriosis Nodules of the Sciatic Nerve: A Three-Dimensional Reconstruction and Surgical Educational Video.” Journal of Minimally Invasive Gynecology 30, no. 4: 264–265. - Nyangoh Timoh, K., C. Paquet, V. Lavoué, C. Touboul, and A. Fauconnier. 2019. “Standardization of Laparoscopic Extrafascial Hysterectomy: Anatomic Considerations to Protect the Ureter.” Surgical and Radiologic Anatomy 41, no. 8: 859–867. - Pinsard, M., N. Mouchet, L. Dion, et al. 2022. “Anatomic and Functional Mapping of Human Uterine Innervation.” Fertility and Sterility 117, no. 6: 1279–1288. - Raimondo, D., A. Raffone, F. Renzulli, et al. 2023. “Prevalence and Risk Factors of Central Sensitization in Women With Endometriosis.” Journal of Minimally Invasive Gynecology 30, no. 1: 73–80.e1. - Ripperda, C. M., L. A. Jackson, J. N. Phelan, K. S. Carrick, and M. M. Corton. 2017. “Anatomic Relationships of the Pelvic Autonomic Nervous System in Female Cadavers: Clinical Applications to Pelvic Surgery.” American Journal of Obstetrics and Gynecology 216, no. 4: 388.e1–388.e7. - Robin, F., L. Dion, V. Lavoue, et al. 2022. “Relationship Between Uterine Veins, Ureter, and Hypogastric Nerve for Uterine Transplantation: An Anatomic Study.” Clinical Anatomy 35, no. 8: 1026–1032. - Robin, F., L. Roux, M. A. Zaheer, et al. 2024. “A Reappraisal of the Deep Uterine Vein: A Multimodal Exploration With Implications for Pelvic Surgery.” Surgical and Radiologic Anatomy 46, no. 3: 381–390. - Shoja, M. M., A. Sharma, N. Mirzayan, et al. 2013. “Neuroanatomy of the Female Abdominopelvic Region: A Review With Application to Pelvic Pain Syndromes.” Clinical Anatomy 26, no. 1: 66–76. - Stratton, P., I. Khachikyan, N. Sinaii, R. Ortiz, and J. Shah. 2015. “Association of Chronic Pelvic Pain and Endometriosis With Signs of Sensitization and Myofascial Pain.” Obstetrics and Gynecology 125, no. 3: 719–728. - Zaitouna, M., B. Alsaid, D. Diallo, G. Benoit, and T. Bessede. 2013. “Identification of the Origin of Adrenergic and Cholinergic Nerve Fibers Within the Superior Hypogastric Plexus of the Human Fetus.” Journal of Anatomy 223, no. 1: 14–21. - Zakhari, A., M. Mabrouk, D. Raimondo, et al. 2020. “Keep Your Landmarks Close and the Hypogastric Nerve Closer: An Approach to Nerve-Sparing Endometriosis Surgery.” Journal of Minimally Invasive Gynecology 27, no. 4: 813–814. Article Metrics Total unique accesses to an article’s full text in HTML or PDF/ePDF format.More metric information Scite metrics Explore this article's citation statements on scite.ai Share QR Code Generating QR code QR code copied to clipboard! Something went wrong while generating your QR code. Please try again in a moment. If the issue persists, refresh the page or contact support. Export citation Unable to load citation data. Please try again in a moment. How to cite Elkins, L. J., & Spiegelman, M. (2021). pyUserCalc: A revised Jupyter notebook calculator for uranium-series disequilibria in basalts. Earth and Space Science, 8, e2020EA001619. https://doi.org/10.1029/2020EA001619 Download Citation If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click on download. This feature enables you to download the bibliographic information (also called citation data, header data, or metadata) for the articles on our site. Citation manager file format Use the dropdown list to choose how to format the bibliographic data you're harvesting. Several citation manager formats are available, including EndNote and BibTex. You can then copy the formatted citation (as displayed) or download it as file, to your device. If the RefWorks format is chosen, the 'Download' button will be replaced with an option to directly export to RefWorks