Oogenesis in Adult Mammals, Including Humans: A Review

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.

Ovarian Stem Cell Niche and Follicular Renewal in Mammals

“…In fetal ovaries, with the support of the immune system related cells, secondary germ cells arise from the somatic OSC. The OSC have been implicated in the formation of oocytes (Allen, 1923;Evans and Swezy, 1931;Everett, 1943;Bukovsky et al, 1995;Bukovsky et al, 2004;Bukovsky et al, 2007), and it also has been suggested that they are a source of granulosa cells (Brambell, 1927;Motta et al, 1980;Bukovsky et al, 1995;Bukovsky et al, 2004;Bukovsky et al, 2005a). As already indicated, numerous small germ cells (10 lm in diameter) are present in OSC layer of human fetal ovaries from 7 to 24 weeks of intrauterine life (Motta and Makabe, 1986).…”

“…1C) entering the rete channels (black and dotted arrowheads, Fig. 1D) are committed by interaction (white arrowhead) with resident memory cells (asterisk; Bukovsky et al, 2005a). Such committed cells (c and cT, Fig.…”

“…One possibility is that such nurse cells in germline cysts help provide oocytes with mitochondria (Pepling and Spradling, 1998). It has been proposed that mitochondria (Bukovsky et al, 2005a). With the onset of secondary germ cell production from the OSC, the primordial germ cells degenerate (X, panel C).…”

“…1C) can migrate (arched arrow) into the OSC layer and exhibit cellular signals (CS) triggering AD of OSC and symmetric division (SD) of secondary germ cells (see below). Emergence of secondary germ cells also requires appropriate hormonal signaling (HS) by hCG and estradiol (Bukovsky et al, 2005a). Emerging secondary germ cells (sgc, panel C) exhibit an ameboid shape and enter the ovarian cortex, where they differentiate into oocytes and meiocytes.…”

“…The egg and follicular renewal apparently ceases after PRP termination due to the alteration of the immune system components in OSC niche (Bukovsky et al, 2005a) associated with early stages of the immune system aging after 35 years of age (Mathe, 1997;, and the remaining eggs are stored until exhausted by a continuing ovarian function (Bukovsky et al, 2004). Much of OSC research has been focused on germ cells, but evidence for stem cell biology with regards to granulosa cells is scant (Chang et al, 2009).…”