A new step toward the artificial ovary Survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold

Fibrin formulations with low concentrations of fibrinogen and thrombin can potentially be used as an artificial ovary, allowing follicle survival and development, cell proliferation, and formation of capillaries.

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Authors

Valérie Luyckx, M.D., Marie-Madeleine Dolmans, M.D., Ph.D., Julie Vanacker, M.Bio.Sc., Ph.D., Camille Legat, Cristina F. Moya, Jacques Donnez, M.D., Ph.D., Christiani A. Amorim, V.M.D., Ph.D.

Volume 101, Issue 4, Pages 1149-1156

Abstract

Objective:

To create an artificial ovary to provide an alternative way of restoring fertility in patients who cannot benefit from transplantation of cryopreserved ovarian tissue due to the threat of reintroducing malignant cells.

Design:

In vivo experimental study.

Setting:

Gynecology research unit in a university hospital.

Animal(s):

Six-week-old female NMRI mice.

Intervention(s):

Autografting of isolated preantral follicles and ovarian cells (OCs) encapsulated in two fibrin matrices containing low concentrations of fibrinogen (F; mg/mL) and thrombin (T; IU/mL): F12.5/T1 and F25/T4.

Main Outcome Measure(s):

Follicular density and development, OC survival and proliferation, inflammatory response, and vascularization.

Result(s):

After 1 week, the follicle recovery rate ranged from 30.8% (F25/T4) to 31.8% (F12.5/T1). With both fibrin formulations, all follicles were found to be alive or minimally damaged, as demonstrated by terminal deoxynucleotide transferase–mediated dUTP nick-end labeling assay, and at the growing stage (primary, secondary, and antral follicles), confirmed by Ki67 immunostaining. Isolated OCs also survived and proliferated after grafting, as evidenced by <1% apoptotic cells and a high proportion of Ki67-positive cells. Vessels were found in both fibrin formulations, and the global vascular surface area varied from 1.35% (F25/T4) to 1.88% (F12.5/T1). Numerous CD45-positive cells were also observed in both F25/T4 and F12.5/T1 combinations. Conclusion(s):

The present study is the first to show survival and growth of isolated murine ovarian follicles 1 week after autotransplantation of isolated OCs in a fibrin scaffold. The results indicate that fibrin is a promising candidate as a matrix for the construction of an artificial ovary. Xenotransplantation of isolated human follicles and OCs is the necessary next step to validate these findings.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)03457-2/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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