Subcutaneous grafting of ovaries from newborn rabbits into adult ovariectomized mice does not result in normal folliculogenesis

Abstract

About 10% (6.1 million) of women in the United States ages 15–44 have difficulty becoming pregnant or staying pregnant. About 1/3 are fertility problems in women. Abnormal ovarian function is a major contributor. A greater understanding of ovarian function and especially follicular development would improve treatment. Follicles form when germ cells arrive in the primitive sex cords, which are derived from the coelomic epithelium. In most species, these cords fragment and the germ cells become covered by precursors of the granulosa cells. Thus primordial follicles form. Pools of these follicles are eventually recruited and undergo maturation; a series of functional and morphological transformations that lead to ovulatory follicles. In species like humans, cattle and pigs, follicles form during the embryonic phase of gestation, while maturation takes place after birth. In contrast, both phases occur postnatally in rabbits and makes them an excellent model to study folliculogenesis. Laboratory studies using non‐rodent species are logistically more difficult and even prohibitive. One alternative is ovarian grafting into immunocompromised mice. When adult ovarian tissue is transplanted from large animals into mice, some primordial follicles survive and undergo maturation. We investigated the rabbit model by transplantation of immature rabbit ovaries under the dorsal skin of adult ovariectomized NCr N ude mice (1 ovary / mouse). At 4 – 5 weeks, growth of the grafted ovaries was evident. Macroscopically, 50% of the grafts (5/10) had one or two follicle‐like structures on their surface. Histologically the structures were cysts lined by cuboidal cells and contained cells with the germ cell phenotype. In conclusion, ovaries grafted subcutaneously from newborn rabbits into ovariectomized adult mice developed cystic primordial follicles. Normal follicle formation and maturation did not occur.Support or Funding InformationMidwestern University intramural funds