Objective: The presence of lymphatic vessels in endometrium has been controversial and recent immunocytochemical studies with routinely paraffin embedded sections revealed lymphatic vessels in basalis and occasionally in functionalis. We aimed to investigate endometrial lymphatic vessels by immunocytochemical staining using cryosections, which provided better and consistent immunostaining for lymphatic vessels with a lymphatic marker, D2-40. We aimed further to explore the structure-function relationship of lymphatic vessels in the menstrual cycle. Materials and Methods: Sixteen cases of endometrium from menstrual, early-proliferative to latesecretary phase were immunostained for D2-40 and lymphatic vessels were morphometrically analyzed for functionalis, basalis and myometrium, respectively. Results: Lymphatic vessels were consistently most numerous in myometrium, followed by basalis in all phases whereas menstrual endometrium showed small, fragmented aggregates of lymphatic vessels in thin basalis. Earlyto mid-secretary endometrium revealed many lymphatic vessels in basalis and lower-functionalis with few lymphatic vessels in upper-functionalis. Late-secretary endometrium revealed more lymphatic vessels in upper-functionalis with dilated walls, which then burst at the surface of functionalis. Conclusions: These degenerating lymphatic vessels with markedly dilated lumen in upper-functionalis may contribute to lymphatic leakage in late-secretary phase. These immunostained lymphatic vessels in functionalis support proliferating and degenerating lymphatic vessel cycle synchronized with the menstrual cycle of endometrial arteries to maintain adequate fluid leakage.
 G. L. Mutter and A. Frenczy, “Anatomy and Histology of the Uterine Corpus,” In: R. J. Kurman, Ed., Blaunstein’s Pathology of the Female Genital Tract, 5th Edition, Springer-Verlag, New York, 2002, pp. 383-419.
 K. Red-Horse, et al., “Cytotrophoblast Induction of Arterial Apoptosis and Lymphangiogenesis in an in Vivo Model of Human Placentation,” The Journal of Clinical Investigation, Vol. 116, No. 10, 2006, pp. 2643-2652.
 M. Koukoulakis, A. Giatromanolaki, E. Sivridis, et al., “LYVE-1 Immunohistochemical Assessment of Lymphangiogenesis in Endometrial and Lung Cancer,” The Journal of Clinical Pathology, Vol. 58, No. 2, 2005, pp. 202-206. http://dx.doi.org/10.1136/jcp.2004.019174
 N. R. Nayak, H. O. D. Critchley, O. D. Slayden, A. Menrad, K. Schwalisz, D. T. Baird and R. M. Brenner, “Progesterone Withdrawal Up-Regulates Vascular Endothelial Growth Factor Receptor Type 2 in the Superficial Zone Stroma of the Human and Macaque Endometrium,” The Journal of Clinical Endocrinology & Metabolism, Vol. 85, No. 9, 2000, pp. 3443-3452.
 O. D. Slayden, N. R. Nayak, K. A. Burton, K. Chwalisz, S. T. Cameron, H. O. D. Critchley, D. T. Baird and R. M. Brenner, “Progesterone Antagonists Increase Androgen Receptor Expression in the Rhesus Macaque and Human Endometrium,” The Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 6, 2001, pp. 2668-2679.
 O. D. Slayden and R. M. Brenner, “Hormonal Regulation and Localization of Estrogen, Progestin and Androgen Receptors in the Endometrium of Nonhuman Primates: Effects of Progesterone Receptor Antagonist,” Archives of Histology and Cytology, Vol. 67, No. 5, 2004, pp. 393-409.
 P. Blackwell and I. Fraser, “Superficial Lymphatics in the Functionalis Zone of Normal Human Endometrium,” Microvascular Research, Vol. 21, No. 2, 1981, pp. 142-152.
 J. E. Garling and P. A. W. Rogers, “The Endometrial Lymphatic Vasculature: Function and Dysfunction,” Reviews in Endocrine and Metabolic Disorders, Vol. 13, No. 4, 2012, pp. 265-275.
 S. Uchino, S. Ishikawa, M. Okubo, Y. Nakamura and A. Iimura, “Methods of Detection of Lymphatics and Their Changes with Oesterous Cycle,” International Angiology, Vol. 6, No. 3, 1987, pp. 271-278.
 A. Marks, D. R. Sutherland, D. Bailey, et al., “Characterization and Distribution of an Oncofetal Antigen (M2A Antigen) Expressed in Testicular Germ Cell Tumors,” British Journal of Cancer, Vol. 80, 1999, pp. 569-578.
 F. E. Frankew, K. Pauls, R. Rey, et al., “Differentiation Markers of Sertoli Cells and Germ Cells in Fetal and Early Postnatal Human Testis,” Anatomy and Embryology (Berl), Vol. 209, No. 2, 2004, pp. 169-177.
 H. J. Kahn and A. Marks, “A New Monoclonal Antibody, D2-40, for Detection of Lymphatic Invasion in Primary Tumors,” Laboratory Investigation, Vol. 82, 2002, pp. 1225-1257.
 A. Urabe, T. Matsumoto, M. Kimura, et al., “Grading System of Lymphatic Invasion according to D2-40 Immunostaining Is Useful for Prediction of Nodal Metastasis in Squamous Cell Carcinomas,” Histopathology, Vol. 49, No. 5, 2006, pp. 493-497.
 T. Tomita, “D2-40 Immunocytochemical Staining for Pancreatic Islets and Pancreatic Endocrine Tumors,” Pancreas, Vol. 38, No. 3, 2009, pp. 39-40.
 S. Podgrabinska, P. Braun, P. Valasco, et al., “Molecular Characterization of Lymphatic Endothelial Cells,” Proceedings of the National Academy of Sciences of the USA, Vol. 99, No. 25, 2002, pp. 16069-16079.
 M. A. A. Al Rawi, R. E. Mansel and W. G. Jiang, “Molecular and Cellular Mechanisms of Lymphangiogenesis,” European Journal of Surgical Oncology, Vol. 31, No. 2, 2004, pp. 117-121.
 T. Karpanen and T. Makinen, “Regulation of Lymphangiogenesis: From Cell Fate Determination to Vessel Remodeling,” Experimental Cell Research, Vol. 312, No. 5, 2006, pp. 575-583.
 R. H. Adams and K. Alitalo, “Molecular Regulation of Angiogenesis and Lymphangiogenesis,” Nature Reviews Molecular Cell Biology, Vol. 8, 2007, pp. 464-478.
 R. M. Brenner, O. D. Slayden, W. H. Rodgers, et al., “Immunocytochemical Assessment of Mitotic Activity with an Antibody to Phosphorylated Histone H3 in the Macaque and Human Endometrium,” Human Reproduction, Vol. 18, No. 6, 2003, pp. 1185-1193.
 O. D. Slayden, T. Koji and R. M. Brenner, “Microwave Stabilization Enhances Immunocytochemical Detection of Estrogen Receptor in Frozen Sections of Macaque Oviduct,” Endocrinology, Vol. 136, No. 9, 1995, pp. 4012-4021. http://dx.doi.org/10.1210/en.136.9.4012
 E. B. Haase, J. Buchman, A. E. Tiez, et al., “PregnancyInduced Uterine Neuronal Degeneration in the Rat,” Cell and Tissue Research, Vol. 288, No. 2, 1997, pp. 293-306.
 R. Rodriguez-Diaz, M. H. Abdulreda, A. L. Frmoso, et al., “Autonomic Axons in the Human Endocrine Pancreas Show Unique Innervation Patterns,” Cell Metabolism, Vol. 14, No. 1, 2011, pp. 45-54.
 T. Tomita, “Localization of Nerve Fibers in Colonic Polyps, Adenomas and Adenocarcinomas,” Digestive Diseases and Sciences, Vol. 57, No. 2, 2012, pp. 364-370.
 S. Breitender-Geleff, A. Soleiman, H. Kawasaki, et al., “Angiosarcomas Express Mixed Endothelial Phenotypes of Blood and Lymphatic Capillaries: Population as a Specific Marker for Lymphatic Epithelium,” The American Journal of Pathology, Vol. 154, No. 2, 1999, pp. 385-394.
 D. Bailey, R. Braumal, J. Law, et al., “Production of a Monoclonal Antibody Specific for Seminomas, Dysgerminomas,” Proceedings of the National Academy of Sciences of the USA, Vol. 83, No. 14, 1986, pp. 5291-5295. http://dx.doi.org/10.1073/pnas.83.14.5291
 P. A. W. Rogers, J. F. Donoghue and J. E. Girling, “Endometrial Lymphangiogenesis,” Placenta, Vol. 29, 2008, pp. s48-s54.
 P. A. W. Rogers, J. F. Donoghue, L. M. Walter, et al., “Endometrial Angiogenesis, Vascular Maturation and Lymphangiogenesis,” Reproductive Sciences, Vol. 16, No. 2, 2009, pp. 147-151.
 J. F. Donoghue, C. J. McGarigan, F. L. Lederman, et al., “Dilated Thin-Walled Blood and Lymphatic Vessels in Human Endometrium: A Potential Role for VEGF-D in Progestin-Induced Break-Through Bleeding,” PLos One, Vol. 7, 2012, p. e30916.
 P. A. Rogers, “Endometrial Vasculature in Norplant Users,” Human Reproduction, Vol. 11, No. S2, 1996, pp. 45-50. http://dx.doi.org/10.1093/humrep/11.suppl_2.45
 S. Schulte-Merker, A. Sabine and T. V. Petrova, “Lymphatic Vascular Morphogenesis in Development, Physiology, and Disease,” The Journal of Cell Biology, Vol. 193, No. 4, 2011, pp. 607-618.
 K. P. Chennazhi and N. R. Nayak, “Regulation of Angiogenesis in the Primate Endometrium: Vascular Endothelial Growth Factor,” Seminars in Reproductive Medicine, Vol. 27, No. 1, 2009, pp. 80-89.
 R. Demir, A. Yaba and B. Huppertz, “Vasculogenesis and Angiogenesis in the Endometrium during Menstrualcycle and Implantation,” Acta Histochemica, Vol. 112, No. 3, 2010, pp. 203-214.
 J. D. Shields, “Lymphatics: At the Interface of Immunity, Tolerance, and Tumor Metastasis,” Microcirculation, Vol. 18, No. 7, 2011, pp. 517-531.