Oogenesis in adult mammals, including humans
ABSTRACT The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries may cause an accumulation of spontaneously arising or environmentally induced genetic alterations of oocytes, and that may be why aging females have a much higher chance of having oocytes with more mutations in persisting primary follicles.
- SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
ABSTRACT: Stem cell niche consists of perivascular compartment, which connects the stem cells to the immune and vascular systems. During embryonic period, extragonadal primordial germ cells colonize coelomic epithelium of developing gonads. Subsequently, ovarian stem cells (OSC) produce secondary germ cells under the influence of OSC niche, including immune system-related cells and hormonal signaling. The OSC in fetal and adult human ovaries serve as a source of germ and granulosa cells. Lack of either granulosa or germ cell niche will result in premature ovarian failure in spite of the presence of OSC. During perinatal period, the OSC transdifferentiate into fibroblast-like cells forming the ovarian tunica albuginea resistant to environmental threats. They represent mesenchymal precursors of epithelial OSC during adulthood. The follicular renewal during the prime reproductive period (PRP) ensures that there are fresh eggs available for a healthy progeny. End of PRP is followed by exponentially growing fetal genetic abnormalities. The OSC are present in adult, aging, and postmenopausal ovaries, and differentiate in vitro into new oocytes. During in vitro development of large isolated oocytes reaching 200 μm in diameter, an ancestral mechanism of premeiotic nurse cells, which operates during oogenesis in developing ovaries from invertebrates to mammalian species, is utilized. In vitro developed eggs could be used for autologous IVF treatment of premature ovarian failure. Such eggs are also capable to produce parthenogenetic embryos like some cultured follicular oocytes. The parthenotes produce embryonic stem cells derived from inner cell mass, and these cells can serve as autologous pluripotent stem cells.The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 08/2011; 294(8):1284-306. DOI:10.1002/ar.21422 · 1.53 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of the study was to examine whether oocyte yield could be an indicator of morphological oocyte quality and biological competency in patients younger than 36 years undergoing controlled ovarian stimulation (COS). Three hundred and thirty-five intracytoplasmic sperm injection (ICSI) procedures were arbitrarily subdivided into five groups according to the number of retrieved oocytes. Patients' demographic characteristics and treatment success were compared among the groups. The influence of the morphological oocyte abnormalities on outcomes was also investigated. The proportion of oocytes that gave rise to viable embryos and high-quality embryos decreased significantly according to oocyte yield. Similarly, the number of foetal heartbeat per retrieved oocyte in fresh embryo transfer cycles was higher in patients with fewer oocytes collected. Finally, a negative correlation was observed between the occurrence of intracytoplasmic oocyte dysmorphisms and the number of foetal heartbeat per oocyte. High oocyte yield may be considered an indicator of low oocyte biological efficiency and intracytoplasmic dysmorphisms may contribute to this biological wastage suggesting that protocols of minimal or mild stimulation should be used.
- [Show abstract] [Hide abstract]
ABSTRACT: A year ago, reproductive biologists and general public were astonished with evidence reported by Johnson et al. in Nature 428:145 that mammalian ovaries possess persisting large germline stem cells, which allegedly enable follicular renewal in adult females. Recently, the same research group declared such view obscure, and reported that mammalian oocytes originate from putative germ cells in bone marrow and are distributed by peripheral blood to the ovaries (Cell 122:303). While neglecting available data on the germ cell origin from the ovarian surface epithelium (OSE) in adult mouse and human females and complexity of follicular renewal in humans, the authors widely extrapolated their observations on formation of allogeneic oocytes after bone marrow (or blood) transplantation in ovaries of adult mice treated with cytostatics to clinical implications in the public media. Yet, the resulting outcome that such allogeneic oocytes may enable the propagation of ovarian cycles is a poor alleviation for the women with ovarian infertility. Women lacking primary follicles, or carrying follicles with low quality eggs persisting in aging ovaries, are not concerned about the lack of menstrual cycles or ovarian steroids, but about virtually no chance of having genetically related children. Johnson et al. also reported that the germ cell formation in bone marrow disappears in ovariectomized mice. Such observation, however, raises solid doubts on the bone marrow origin of oocytes. Since germ cells developing from the OSE cells of adult human ovaries during periodical follicular renewal are known to enter blood vessels in order to enable formation of primary follicles at distant ovarian sites, they also contaminate peripheral blood and hence bone marrow. Better knowledge on the complexity of follicular renewal in humans and exploration of a potential of human OSE cells to produce new oocytes in vitro are essential for novel approaches to the autologous treatment of premature ovarian failure and age induced ovarian infertility.Reproductive Biology and Endocrinology 02/2005; 3:36. DOI:10.1186/1477-7827-3-36 · 2.41 Impact Factor