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Do germ line stem cells exists or is the number of eggs in women limited?

Almost one year ago Facebook and Apple announced that they will cover the cost of egg freezing for their female employees [1]. Egg freezing is seen as a way to improve the success of a potential future in-vitro fertilization (IVF) procedure by using an egg that is years, even decades, younger than the mother. However, this approach is based on a not yet solid assumption: That a woman’s eggs are produced during fetal development and, as direct consequence, gain in age (and loose in fertility) with the woman that carries them [2, 3]. The age of first-time parents is rising in our time, which entails growth of the IVF industry that seeks to ensure fertility of women that are rather at the end of their reproductive age [4].

What if IVF could be circumvented by letting the body generate new eggs? This process would require appropriate stem cells that are able to divide. Whether such cells exist is still a matter of debate. In 2005 the group of Jonathan L. Tilly identified bone marrow transplantation as source for stem cells that restore fertility in sterilized mice [5]. The same group claimed to have identified actively dividing germ cells in the ovaries of reproductive age women, that were capable to develop into eggs [6].

The hoped-for natural substitute of IVF seemed found at last, but was soon challenged by Zhang et al., who could disprove the existence of dividing stem cell precurors in mice [7]. In fact another paper confirmed that mouse oogenesis originates from cells that are already formed at birth [8]. Thus the debate remains open, with some scientists claiming that “absence of evidence is not evidence of absence” [9]. Current evidence arguing for or against non-renewable ovary stores in mammals is reviewed in [10].

Felix Spenkuch

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[1] (called at 8.07.2015)

[2] S. Zuckerman (1951) The number of oocytes in the mature ovary. Recent Prog. Horm. Res. 6, 63-108.

[3] S. Zuckerman, T. G. Baker (1977) The development of the ovary and the process of oogenesis. The Ovary, Academic Press, New York, 41-67.

[4] (called at 8.07.2015)

[5] J. Johnson et al. (2005) Oocyte Gerneration in Adult Mammalian Ovaries by Putative Germ Cells in Bone Marow and Peripheral Blood. Cell. 122, 303-315.

[6] Y. A. R. White et al. (2012) Oocyte formation in mitotically active germ cells purified from ovaries of reproductive-age women. Nature Medicine, 18, 413-421.

[7] Zhang et al. (2012) Experimental evidence showing that no mitotically active female germline progenitors exits in postnatal mopuse ovaries. Proc Natl Acad Sci USA, 109, 12580-12858.

[8] Lei Lie and A. C. Spradling (2013) Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc Natl Acad Sci USA, 8585-8590.

[9] D. Bhatiya et a. (2013) Ovarian stem cells: absence of evidence is not evidence of absence. J Ovarian Res, 6:65.

[10] C. B. Hanna, J. D. Hennebold (2014) Fertility and Sterility, 101, 20-30.