Korean J Transplant.  2023 Jun;37(2):109-117. 10.4285/kjt.23.0019.

Anatomic characteristics and novel transplantation model of the canine uterus

• Do XH
• Tong TH
• Nguyen TC
• Ngo TA
• Thi Tran MT

• KMID: 2544115
• DOI: http://doi.org/10.4285/kjt.23.0019

Abstract

Background
In Vietnam, the rate of absolute uterine factor infertility is increasing, but no study has been published on uterine transplantation. The present study was designed to comprehensively observe the canine uterine anatomy and to examine the possibility of using a living canine donor for uterine transplantation training and further research.
Methods
Ten female Vietnamese mixed-breed dogs were sacrificed for anatomical research, and 15 additional pairs were used to evaluate the novel uterine transplant model.
Results
The anatomic features of the canine uterus differed considerably from those of the human uterus, with the uterine vessels originating from branches of the pudendal vessels (also known as the vaginal vessels). The uterine vascular pedicle had a small diameter (1 to 1.5 mm for arteries and 1.2 to 2.0 mm for veins) and required manipulation under a microscope. To perform uterine transplantation, the donor specimen’s artery and vein lengths were successfully reconstructed by anastomosis between both sides of the vasculature using autologous Y-shaped subcutaneous veins. The living-donor uterine transplantation model constructed in this study was feasible, with the transplanted uterus surviving in 86.7% of cases (13/15).
Conclusions
Uterine transplantation was successfully performed in a Vietnamese canine living donor model. This model could be helpful in uterine transplantation training and improve the transplantation success rate in humans.

Keyword

Infertility; Uterus; Transplantation; Living donor; Dogs

Figure

• 

  Fig. 1 (A) Uterine anatomy of a Vietnamese dog. (B) Vascular structure of the uterus.

• 

  Fig. 2 Organ procurement. (A) Infusion of 4 °C Ringer lactate solution with 2% lidocaine into arteries (blue needle) and veins (yellow needle) until the water was clear and the uterus was white and pink, then arterial infusion with 4 °C Custodiol (Dr. Franz Köhler Chemie GmbH) solution. (B) Organ procurement time for each donor dog.

• 

  Fig. 3 Donor uterus and venous graft for augmentation of the vascular pedicle. (A) Experimental canine donor uterus graft model with arterial Y-graft. (B) Donor’s venous graft under ×10 magnification. Arrow: Y-graft anatomoses; 1 and 2: the two branches of the Y-graft; 3: mesometrium. (C) Length of the graft pedicle after angioplasty.

• 

  Fig. 4 Operative times in minutes (first warm ischemic time, cold ischemic time, and duration of implantation) for each operated dog.

• 

  Fig. 5 (A) X-ray image after uterus transplant on day 5. (B) Images of contrast enhancement of the transplanted canine uterus after 15 minutes.

Reference

1. Brannstrom M, Johannesson L, Dahm-Kahler P, Enskog A, Molne J, Kvarnstrom N, et al. 2014; First clinical uterus transplantation trial: a six-month report. Fertil Steril. 101:1228–36. DOI: 10.1016/j.fertnstert.2014.02.024. PMID: 24582522.

2. Brannstrom M, Johannesson L, Bokstrom H, Kvarnstrom N, Molne J, Dahm-Kahler P, et al. 2015; Livebirth after uterus transplantation. Lancet. 385:607–16. DOI: 10.1016/S0140-6736(14)61728-1. PMID: 25301505.

3. Favre-Inhofer A, Carbonnel M, Domert J, Cornet N, Chastant S, Coscas R, et al. 2022; Involving animal models in uterine transplantation. Front Surg. 9:830826. DOI: 10.3389/fsurg.2022.830826. PMID: 35284480. PMCID: PMC8904568.

4. Zhordania IF, Gotsiridze OA. 1964; Vital activity of the excised uterus and its appendages after their autotransplantation into omentum. Experimental research. Acta Chir Plast. 6:23–32.

5. Eraslan S, Hamernik RJ, Hardy JD. 1966; Replantation of uterus and ovaries in dogs, with successful pregnancy. Arch Surg. 92:9–12. DOI: 10.1001/archsurg.1966.01320190011002. PMID: 5948103.

6. Barzilai A, Paldi E, Gal D, Hampel N. 1973; Autotransplantation of the uterus and ovaries in dogs. Isr J Med Sci. 9:49–52.

7. Truta E, Pop I, Popa D, Ionescu M, Truta F. 1969; Experimental re- and transplantation of the internal female genital organs. Rom Med Rev. 13:53–8.

8. Yonemoto RH, Du Sold WD, Deliman RM. 1969; Homotransplantation of uterus and ovaries in dogs: a preliminary report. Am J Obstet Gynecol. 104:1143–51. DOI: 10.1016/S0002-9378(16)34288-0. PMID: 5799618.

9. Wall AE, Testa G, Axelrod D, Johannesson L. 2021; Uterus transplantation-questions and answers about the procedure that is expanding the field of solid organ transplantation. Proc (Bayl Univ Med Cent). 34:581–5. DOI: 10.1080/08998280.2021.1925064. PMID: 34456477. PMCID: PMC8366946.

10. Ozkan O, Dogan NU, Ozkan O, Mendilcioglu I, Dogan S, Aydinuraz B, et al. 2016; Uterus transplantation: from animal models through the first heart beating pregnancy to the first human live birth. Womens Health (Lond). 12:442–9. DOI: 10.1177/1745505716653849. PMID: 27638900. PMCID: PMC5373276.

11. Racho El-Akouri R, Kurlberg G, Brännström M. 2003; Successful uterine transplantation in the mouse: pregnancy and post-natal development of offspring. Hum Reprod. 18:2018–23. DOI: 10.1093/humrep/deg396. PMID: 14507815.

12. Groth K, Brannstrom M, Molne J, Wranning CA. 2010; Cyclosporine A exposure during pregnancy in mice: effects on reproductive performance in mothers and offspring. Hum Reprod. 25:697–704. DOI: 10.1093/humrep/dep470. PMID: 20085916.

13. Wranning CA, El-Akouri RR, Lundmark C, Dahm-Kahler P, Molne J, Enskog A, et al. 2006; Auto-transplantation of the uterus in the domestic pig (Sus scrofa): surgical technique and early reperfusion events. J Obstet Gynaecol Res. 32:358–67. DOI: 10.1111/j.1447-0756.2006.00426.x. PMID: 16882260.

14. Wranning CA, Marcickiewicz J, Enskog A, Dahm-Kahler P, Hanafy A, Brännström M. 2010; Fertility after autologous ovine uterine-tubal-ovarian transplantation by vascular anastomosis to the external iliac vessels. Hum Reprod. 25:1973–9. DOI: 10.1093/humrep/deq130. PMID: 20519245.

15. El-Akouri RR, Kurlberg G, Dindelegan G, Molne J, Wallin A, Brannstrom M. 2002; Heterotopic uterine transplantation by vascular anastomosis in the mouse. J Endocrinol. 174:157–66. DOI: 10.1677/joe.0.1740157. PMID: 12176655.

16. Wranning CA, Akhi SN, Diaz-Garcia C, Brannstrom M. 2011; Pregnancy after syngeneic uterus transplantation and spontaneous mating in the rat. Hum Reprod. 26:553–8. DOI: 10.1093/humrep/deq358. PMID: 21159686.

17. Miyauchi Y, Noda T, Miura N, Kikugawa T, Saika T. 2021; Venous reconstruction using a Y-shaped saphenous vein in kidney transplantation: a report of three cases. IJU Case Rep. 4:146–9. DOI: 10.1002/iju5.12266. PMID: 33977243. PMCID: PMC8088897.

18. Brucker SY, Brannstrom M, Taran FA, Nadalin S, Konigsrainer A, Rall K, et al. 2018; Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval. Arch Gynecol Obstet. 297:675–84. DOI: 10.1007/s00404-017-4626-z. PMID: 29270725.

19. Chmel R, Novackova M, Janousek L, Matecha J, Pastor Z, Maluskova J, et al. 2019; Revaluation and lessons learned from the first 9 cases of a Czech uterus transplantation trial: four deceased donor and 5 living donor uterus transplantations. Am J Transplant. 19:855–64. DOI: 10.1111/ajt.15096. PMID: 30151893.

20. Feuillu B, Cormier L, Frimat L, Kessler M, Amrani M, Mangin P, et al. 2003; Kidney warming during transplantation. Transpl Int. 16:307–12. DOI: 10.1111/j.1432-2277.2003.tb00305.x. PMID: 12759721.

21. Dion L, Le Lous M, Nyangoh Timoh K, Levêque J, Arnaud A, Henri-Malbert C, et al. 2021; Single bilateral ovarian venous return in uterine transplant: validation in an orthotopic auto-transplant model in the Yucatan minipig. J Gynecol Obstet Hum Reprod. 50:102059. DOI: 10.1016/j.jogoh.2021.102059. PMID: 33421624.

22. Andraus W, Ejzenberg D, Santos RM, Mendes LR, Arantes RM, Baracat EC, et al. 2017; Sheep model for uterine transplantation: the best option before starting a human program. Clinics (Sao Paulo). 72:178–82. DOI: 10.6061/clinics/2017(03)08.

23. Favre-Inhofer A, Carbonnel M, Revaux A, Sandra O, Mougenot V, Bosc R, et al. 2018; Critical steps for initiating an animal uterine transplantation model in sheep: experience from a case series. Int J Surg. 60:245–51. DOI: 10.1016/j.ijsu.2018.11.017. PMID: 30481612.

24. Fageeh W, Raffa H, Jabbad H, Marzouki A. 2002; Transplantation of the human uterus. Int J Gynaecol Obstet. 76:245–51. DOI: 10.1016/S0020-7292(01)00597-5. PMID: 11880127.

25. Mäkikallio K, Tekay A, Jouppila P. 2004; Uteroplacental hemodynamics during early human pregnancy: a longitudinal study. Gynecol Obstet Invest. 58:49–54. DOI: 10.1159/000077914. PMID: 15087597.