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.
"The OSC niche in adult ovaries consists of MDC, including primitive (CD14 þ ) and activated (HLA-DR þ ) ones, and T cells assisting AD of OSC developing from ovarian TA. In contrast to testis exhibiting continuous gametogenesis, the development of new secondary germ cells is reserved for a limited period during each cycle, since it requires high levels of circulating estradiol and LH only available during the periovulatory period (Bukovsky et al., 2005a). The difference between fetal and adult stem cell niche is the following: To form primordial follicles in fetal ovaries , the germ cells are migrating themselves a relatively short distance between the ovarian surface and adjacent cortex, where numerous granulosa cells are available. "
[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 · 1.54 Impact Factor
"In contrast, during ovarian stimulation for ART these follicles are rescued, but their oocytes may be already intrinsically abnormal (Kovalevsky & Patrizio 2005; Patrizio et al., 2007). The ability to reinitiate the meiotic process and undergo preimplantation development is also progressively determined during the antral phase (Bukovsky et al., 2005). These changes involve both the nuclear and cytoplasmic compartments, but the underlying molecular dynamics are still poorly understood. "
[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.
that during asymmetric division the emerging germ cells daughters (red
asterisks) are substantially larger than OSC daughter cells (yellow asterisks). The activated (HLA-DR+) MDC are associated with growing (gf and arrowheads,
panel G) but not resting primordial follicles (pf) [36,70]. "
[Show abstract][Hide abstract] ABSTRACT: The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.
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