I periodically indulge myself in the personal lives of the Seattle Grace Hospital staff on Grey’s Anatomy. I am particularly fond of the character Dr. Addison Montgomery, world-class neo-natal surgeon. After enduring some juicy relationship drama, Addison decides to have a baby, which sends her on a journey to California where she visits a fertility specialist, a journey I have followed in the spin-off series Private Practice. Sadly, Addison is unable to get pregnant and much of her storyline focuses on her trials and disappointments as she undergoes fertility treatments and adoption application.
While some of Dr. Montgomery’s medical dilemmas are a bit far-fetched, her infertility story is becoming more common in the real world as infertility rates increase. A study published earlier this year in Human Reproduction reported a dramatic increase in the prevalence of infertility, from 5.4% in 1984 to 8.5% in 1992 and then up to 15.7% in 2009.
When it comes to female fertility, it was long thought that women are born with a finite number of ovarian follicles (the structures that contain maturing oocytes, or eggs). But last February, a study in Nature Medicine challenged this dogma with the first report of a human ovarian stem cell, a stem cell harbouring the potential to produce mature oocytes.
The ability to generate mature oocytes from stem cell sources has the potential to revolutionize assisted reproductive technologies. And this month, another advance towards this vision was published in Science, the generation of functional oocytes from mouse pluripotent stem cells.
Proof that an oocyte is capable of generating viable and fertile offspring is required for an oocyte to be labeled as functional. While the reported procedure is by no means straightforward, the end result is indeed functional oocytes.
The recipe for pluripotent stem cell-derived oocytes is as follows: Differentiate pluripotent stem cells into primordial germ cell-like cells (germ cell progenitors) and culture one part primordial germ cell-like cells with one part embryonic ovarian cells for three days. To create fertile offspring: Transplant cell mixture into a mouse ovary for 4½ weeks. Remove oocyte-like cells derived from pluripotent stem cells and perform in vitro maturation and fertilization. Following embryo transfer to foster mothers, newborn (mouse) pups are generated at an efficiency of ~4% (wild-type embryos generate newborn pups at an efficiency of ~17%).
While the use of embryonic ovarian tissue will make this difficult for human pluripotent stem cell application, studying this culture system in the mouse could identify which signals are required from embryonic tissue, critical knowledge that could allow researchers to try to mimic these signals with growth factors and small molecules in order to generate functional oocytes from human pluripotent stem cells.
As more women put off starting a family to pursue higher education and establish careers, the combination of advanced maternal age (the age at which a woman bears her first child) with an increase in infertility is making it difficult for many women to bear children. While putting off child rearing, some women may keep the comfort of assisted reproductive technologies in the back of their mind, however, the success rate of assisted conception also dramatically decreases with age.
The discoveries of ovarian stem cells and the ability to generate functional oocytes from pluripotent stem cells provide powerful tools for understanding female reproductive biology and may even one day allow more women to start families.
Angela C. H. McDonald
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