Biomedical Engineering Reference
In-Depth Information
13.2.2 Ovarian Stem Cells in Postnatal Life?
Until less than 10 years ago, it was accepted as true that the adult mammalian ovary
did not contain self-renewing stem cells. According to this long-held dogma in
reproductive biology, females are born with a finite population of non-growing
follicles that declines with age. In 2004, Tilly's group provided evidence to challenge
this doctrine. They showed that, in adult mouse ovaries, neo-oogenesis actually takes
place from ovarian stem cells (OSCs) located in the surface epithelium of the ovary
(OSE) [
121
]. Furthermore, the same group claimed the formation of immature
oocytes after bone marrow transplantation, suggesting an extraovarian source of
OSCs [
122
,
123
]. However, later, it was stated that bone marrow cells were not
involved in oocyte formation, but that they improve the function of the ovary after
chemotherapy-induced damage [
124
,
125
]. Another report hypothesizes that a small
number of PGCs remain in the postnatal ovary, which are able to resume mitosis,
enter meiosis, and give rise to oocytes [
126
] (Fig.
13.6
).
It has been reported that, in human, the OSE shows characteristics of both
mesenchymal and epithelial cells. The mesenchymal cells in the OSE were found
to be capable of developing into OSCs by a mesenchymal-epithelial transition,
giving rise to oocytes and de novo folliculogenesis [
127
,
128
]. Even when OSE
cells were put in culture, some of the cells were able to form oocyte-like cells
[
129
]. Recently, VASA-positive cells could be purified from neonatal and adult
mouse ovaries and maintained in culture for months. The transplantation of these
cultured cells in chemotherapy-sterilized recipients led to the development of
oocytes and the production of viable offspring [
130
].
While the presence of PGC-derived stem cells in the ovary is scrutinized [
131
],
neo-oogenesis in the adult ovary remains a matter of big controversy.
13.2.3 Fertility Preservation and Restoration in Girls
In prepubertal girls ovarian tissue cryopreservation is available. The technique
involves surgical removal of the cortex containing the immature follicles. After
being dissected, the cortex is cut into thin strips and cryopreserved by slow
freezing or vitrification. Potential future use of the tissue includes autotransplan-
tation onto the remaining ovary or to a heterotopic site. The former strategy has
already led to the first pregnancies and life births [
132
]. In the latter case, the
administration of gonadotrophins is required to stimulate follicular development.
The oocytes are harvested and used for in vitro fertilization [
133
,
134
].
In analogy with testis tissue transplantation in male cancer survivors, the risk of
reintroducing malignant cells should be taken into consideration. An alternative
strategy, currently under development, is in vitro maturation of primordial follicles
[
135
]. Mouse ovarian strips and isolated follicles cultured in a 3D matrix generated
mature oocytes, which could be fertilized and yielded healthy life offspring [
136
,
137
].
