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. 2019 Mar 28;9:5302. doi: 10.1038/s41598-019-40457-1

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Reproductive organ defects in Gdnf ^wt/hyper mice. (A) Male wild type (WT) lower urinary tract and reproductive organs at P10. Black arrow denotes ureter (u) connection to bladder (bl). (B) Gdnf ^wt/hyper male in F2 generation exhibits split ureter with one (u, black arrow) connecting to bladder (bl) and the other, hydroureter (u) connecting to vas deferens (vd, red arrow). (C) Hematoxylin-eosin staining of P56 wild type seminal vesicle. Squared area is enlarged in C’. (D) Histology of P56 Gdnf ^wt/hyper seminal vesicle shows sperm inside the lumen and loss of typical lobular shape of seminal vesicles. Squared area is enlarged in D’. (E) Normal female mouse abdomen at P35. Yellow arrows point to uterus, white arrows indicate ureter. (F) Corresponding abdomen of Gdnf ^wt/hyper female shows hydrotic ureters and badly swollen uteri (yellow arrows). Hematoxylin-eosin staining of frontal sections of (G) WT and (H) Gdnf ^wt/hyper vagina at the surface level. Asterisk in H shows accumulation of keratinized mass inside the vagina, which is indicative of fluid blockage. Black arrows point to vaginal opening in wild type mice, and to the site where vaginal opening should be in Gdnf ^wt/hyper mice. All images are examples of F2 generation of backcrossing to isogenic C57BL/6NCrl background. Abbreviations: bl; bladder, sp; sperm, sv; seminal vesicle, t; testis, u; ureter, ut; uterus, vd; vas deferens. Scale bars: 1 mm and C’: 250 µm.