Setting the Record Straight on Data Supporting Postnatal Oogenesis in Female Mammals

Abstract

Of all the 'certainties' in mammalian female reproductive biology, the concept that a non-renewing oocyte reserve is set forth in the ovaries at birth may be the most longstanding and widely held. However, when data from our studies of oocyte apoptosis unintentionally began to contradict this theory in the latter part of 2002, we embarked on an investigation, unbiased by any pre-conceived dogmas, to determine if oocyte production persists in adult female mice. In 2004, we presented our first experimental findings in the journal Nature, which indicated that oogenesis indeed continues in adulthood. Amidst widespread skepticism, we moved forward with our studies and this year published our follow-up experiments in the journal Cell. Results from this latter body of work not only reinforced our earlier conclusions but also identified bone marrow as a surprising source of oocyte-producing germ cells in adults. Although this study has also been met with skepticism, doubts raised in commentaries on our work are largely based on inaccurate or incomplete assessments of our experimental models and results. Here we have attempted to clarify published misperceptions and misinterpretations of our data, and offer additional insights that challenge the idea of fixed endowment of oocytes at birth.

Global Deletion of Trp53 Reverts Ovarian Tumor Phenotype of the Germ Cell–Deficient White Spotting Variant (Wv) Mice

“…Oocytes recruit and become surrounded by granulosa cells to form follicles in late embryogenesis for humans and the immediate neonatal period for mice [9] . Thus, a finite population of oocytes is established at birth, although this paradigm has been challenged and the controversy has not yet been resolved [10] , [11] , [12] . Nevertheless, after birth, the majority of the oocytes in mammals are progressively lost by atresia, and only a fraction of the follicles in the ovarian reserve develop to maturity and are used in ovulation [13] , [14] .…”

Seeking the origin of female germline stem cells in the mammalian ovary

“…From this perspective, it will be critical to elucidate which are the differential molecular mechanisms that allow a PGC to escape the signalling that induces meiotic commitment and instead of oogonia characteristics induces female PGCs to adopt a gonocyte-like phenotype. It might be that the quiescent state of putative mouse FGSCs is maintained through modulation of chromatin structure, particularly by histone deacetylation, and through R126 M De Felici and F Barrios inhibition of CDK2 (Johnson et al 2005b, Lee et al 2007). In the male germ line, spermatogonial stem cells (SSCs) originating from PGCs are intrinsically pluripotent and posses both cell cycle quiescence and self-renewal capability; in SSCs, however, imprinting is already partly re-established (Davis et al 2000, Kerjean et al 2000.…”

“…Three recipients were killed 3 days after the injection, and their ovaries were fixed overnight in 4% paraformaldehyde at 4 8C. After embedding in paraffin, serial sections were cut as described in Johnson et al (2005aJohnson et al ( , 2005b. Sectioned ovaries were stained for anti-GFP with WT and TgOG2 sections in parallel in every slide.…”

New Facts About Ovarian Stem Cells: The Origin and the Fate

“…Thus, in recent years, research on the ovary and stem cells has been very challenging. In recent years, Johnson et al (28) presented some evidence about presenting of germ cells and their proliferation in the ovaries of adult mice and also their participation in the ovarian reserve after birth. A study demonstrated that 7 to 100 days after birth, no reduction occurred in the number of primordial follicles in the ovaries of mice.…”