Bone Marrow Derived Cells and Alternative Pathways of Oogenesis in Adult Rodents

Abstract

Oocyte generation in adult mouse ovaries by putative germ cells (PGCs) in bone marrow and peripheral blood has recently been proposed. It, however, remains unclear whether in laboratory rodents the PGCs reside in BM or the BM cells stimulate oogenesis from ovarian stem cells. We utilized immunoperoxidase staining to localize PGCs, oocytes, and BM derived cells in ovaries of adult (age 45-60 days) control and neonatally estrogenized rat females. In controls, BM derived cells accompanied emergence of PGCs from the ovarian surface epithelium (OSE) cells. The PGCs divided symmetrically, separated, and formed primordial follicles. A proportion (50%) of adult neonatally estrogenized rats lacked OSE. They exhibited occurrence of numerous BM derived cells and appearance of PGC precursors in the medulla. In juxtaposed deep ovarian cortex the emerging PGCs exhibited distinct pseudopodia and apparently migrated toward the mid cortex, where numerous primordial follicles were found. These observations indicate that BM derived cells accompany origination of PGCs from the OSE stem cells in normal adult rat females and from the medullary precursors in the adult neonatally estrogenized rats lacking OSE. An alternative origin of PGCs from the medullary region may explain why ovaries with destructed OSE are still capable of forming new primordial follicles.

Ovarian Stem Cell Niche and Follicular Renewal in Mammals

“…Regarding the argument (2) that OSC are not essential for neo-oogenesis since the oocytes persist in ovaries lacking OSC, we demonstrated that in rat ovaries lacking OSC the oocytes originate by an alternate pathway, from medullary somatic stem cells, and primordial follicles are formed in the juxtaposed deep ovarian cortex (Bukovsky et al, 2007).…”

“…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).…”

“…Although the ''storage'' concept on the preservation of oocytes from the period of ovarian development in humans and most other mammalian species is still prevailing, the studies of follicular renewal during adulthood in humans (Bukovsky et al, 1995(Bukovsky et al, , 2004(Bukovsky et al, , 2008a and laboratory rodents (Johnson et al, 2004(Johnson et al, , 2005Bukovsky et al, 2005aBukovsky et al, , 2007Kerr et al, 2006) have awoken the curiosity of many scientists globally.…”

“…Regarding point (4), step-by-step oogenesis and follicular renewal from somatic OSC have been described in fetal and adult human and adult rat ovaries (Bukovsky et al, 1995(Bukovsky et al, , 2004(Bukovsky et al, , 2007.…”

“…Finally, regarding query (5), the mitotic division of newly formed germ cells and oogonia has been described in human and rat ovaries (Bukovsky et al, 2004(Bukovsky et al, , 2007.…”