Subcutaneous ovarian tissue transplantation in nonhuman primates: duration of endocrine function and normalcy of subsequent offspring as demonstrated by reproductive competence, oocyte production, and telomere length
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The main purposes of the study were to investigate the endocrine function of ovarian tissue transplanted to heterotopic subcutaneous sites and the reproductive competence and telomere length of a nonhuman primate originating from transplanted tissue.
Ovarian cortex pieces were transplanted into the original rhesus macaques in the arm subcutaneously, in the abdomen next to muscles, or in the kidney. Serum estradiol (E2) and progesterone (P4) concentrations were measured weekly for up to 8 years following tissue transplantation. A monkey derived from an oocyte in transplanted ovarian tissue entered time-mated breeding and underwent controlled ovarian stimulation. Pregnancy and offspring were evaluated. Telomere lengths and oocytes obtained following controlled ovarian stimulation were assessed.
Monkeys with transplants in the arm and abdomen had cyclic E2 of 100 pg/ml, while an animal with arm transplants had E2 of 50 pg/ml. One monkey with transplants in the abdomen and kidney had ovulatory cycles for 3 years. A monkey derived from an oocyte in transplanted tissue conceived and had a normal gestation until intrapartum fetal demise. She conceived again and delivered a healthy offspring at term. Controlled ovarian stimulations of this monkey yielded mature oocytes comparable to controls. Her telomere length was long relative to controls.
Heterotopic ovarian tissue transplants yielded long-term endocrine function in macaques. A monkey derived from an oocyte in transplanted tissue was reproductively competent. Her telomere length did not show epigenetically induced premature cellular aging. Ovarian tissue transplantation to heterotopic sites for fertility preservation should move forward cautiously, yet optimistically.
KeywordsOvarian tissue transplantation Steroid hormone Fertility Telomere Primate
We are grateful for the assistance provided by members of the Division of Comparative Medicine, the Endocrine Technology Support Core, the ART Support Core, and the Biostatistics and Bioinformatics Unit at ONPRC. We appreciate Drs. Theodore R. Hobbs, Dave L. Hess, and Byung S. Park for their valuable expertise.
This work was supported by the National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) UL1 RR024926 (the Oncofertility Consortium: RL1 HD058293, HD058295, PL1 EB008542), NIH NICHD through cooperative agreement as part of the Specialized Cooperative Center Program in Reproduction and Infertility Research U54 HD18185, NIH Office of the Director P51OD011092 (Oregon National Primate Research Center), and the Bidwell Foundation.
Compliance with ethical standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
Conflict of interest
The authors declare that they have no conflict of interest.
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