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How to Scramble 50 Years of Reproductive Science

Rightly or wrongly, some women feel that pursuing a career conflicts with their desire to have children. Those years when their careers could be soaring coincide with what may be their last chance to conceive.

The belief that the female sex cell (oogonium) is non-renewable has plagued professional women and delighted IVF physicians over the last 30 years. Recent evidence suggests a revolutionary paradigm shift may be about to unfold in our understanding, teaching and application of reproductive physiology.

In 2004, a study published in Nature set out to disprove the longstanding belief that the human female is born with a finite number of eggs. Female mice were found to possess rare oogonial stem cells (OSCs) capable of producing mature eggs in much the same way as sperm stores are replenished in the male testes. This study flew in the face of more than 50 years of acceptance that the neonatal ovarian reserve is on a one-way trip to the menopause.

Corroborative evidence for these findings was released in 2009 and 2010 when isolated OSCs were found to multiply when stored in the appropriate in vitro (isolated from the body) conditions for a number of months. Furthermore, these OSCs were capable of producing new oocytes without external stimulation. Transfer of these in vitro oocytes into mice sterilised by chemotherapy resulted in normal oocyte maturation, fertilisation and the birth of live offspring.

While the mouse model continues to be critical for scientific advancement, fate would also have it the little mouse  laid the foundations for greater study of human female OSCs. In March 2012, American and Japanese scientists published a study in Nature Medicine which confirmed the presence of proliferating stem cells in human ovaries.

To prove that new oocytes can arise from human OSCs, tissue grafts (xenografts) were taken from human ovaries and transferred to female mice. The grafts were assessed 7 to 14 days later for positive expression of a special Green Fluorescent Protein (GFP) when exposed to ultraviolet light. GFP expression was observed in xenografted OSCs which confirmed that mitotic activity was observable in generated oocytes.

The potential for this new evidence to reverse the aging of human ovaries, may offer women who are rendered infertile through medical treatment or age another chance to conceive biologically. This prospect would have been unthinkable a decade ago when the options available for infertile women were limited to adoption or the receipt of a donor egg. There’s hope that further advances in this field may lead to a future where age is no longer a determining factor in human conception.

Oliver Timms

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