Abstract
In several canine models of hereditary human disease the homozygote dogs die prior to puberty, or have substantially reduced fertility. To create a clinically healthy animal that can be bred, but can also transmit the gene of interest, a model of homologous ovarian transplantation in prepubertal dogs was developed. Six dog leukocyte antigen (DLA) identical littermates underwent transplantation of ovarian cortical strips (n = 2) or the entire ovary (n = 4). Immunosuppression was maintained with cyclosporine and MMF in the immediate post-operative period and cyclosporine alone thereafter. All 6 dogs entered puberty and normal semiannual estrus cycles as demonstrated by both physical changes and increasing serum progesterone. Four dogs were bred to a proven stud male, and one became pregnant. Three viable fetuses with observable heartbeats were detected on ultrasound examination. Although the dog eventually aborted the litter, this work represents the first pregnancy achieved following a prepubertal ovarian transplant in the dog.
Highlights
Animal models are critical to the study of inherited human disease
There has been an enormous increase in research involving genetically engineered mice as models of inherited human disease; canine models are still utilized throughout the biomedical community
The results of this study demonstrate that canine prepubertal ovarian transplantation can result in pregnancy
Summary
Animal models are critical to the study of inherited human disease. As a result, there has been an enormous increase in research involving genetically engineered mice as models of inherited human disease; canine models are still utilized throughout the biomedical community. Four of the six ovary transplant recipients were bred (n = 2 en bloc method; n = 2 cortical strip method), while for the remaining two (en bloc method), behavioral estrus was not detected in a timely way The latter dogs exhibited serum progesterone levels above 5 ng/ml, indicating that the ovaries were functional but that the dogs were beyond estrus. The surgical procedure employed in the present study utilized the natural opening in the ovarian bursa, near the fimbriae, as a site for removal of the recipient ovary and insertion of the donor organ This natural opening was sutured closed to secure the ovary, a process that may have resulted in scar tissue formation which obstructed the opening to the oviduct.
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