tell a woman how long it will remain so.
Because of these current deficiencies in our understanding,
there is a great need to identify the genes and proteins respon-
sible for controlling egg loss, both during ovarian development
in the foetus and postnatal life. Our laboratories have found that
preventing the natural loss of eggs early in life, by manipulating
key death pathways in the egg, can extend the fertile lifespan –
at least in mice.
We have found that two cell death-promoting proteins
called PUMA and BMF play an important role in determining
how many eggs are initially established and then maintained
in the ovary. In mice, elimination of PUMA prevents the natural
loss of eggs in the developing embryo, and consequently females
are born with twice as many eggs as normal. Interestingly, these
excess eggs are eliminated prior to adulthood by an unknown
mechanism, with loss of fertility occurring at the normal age.
In contrast, BMF-deficient mice are born with normal egg
numbers, but the rate of egg loss after birth is reduced. This
means that more eggs are maintained in the ovary throughout
reproductive life, and fertility is prolonged by approximately 2
months. While this may not seem like much, it equates to a
25% longer fertile lifespan in the mouse. In women, this would
mean extending the fertile lifespan by as many as 6 years.
While extending the length of the fertile lifespan in women
using this strategy is not feasible, our work demonstrates that
reducing egg loss early in life leads to increased egg availability
in adulthood, which confers longer fertility.
Furthermore, it has been known for many years that situa-
tions in which egg number is severely depleted, such as through
exposure to anti-cancer treatments, often lead to early loss of
fertility and menopause, but it was not clear if the converse –
increasing egg number – would lead to longer fertility. Studies
such as ours provide support for the idea that egg number does
play a significant role in controlling the fertile lifespan.
While conceptually this is a significant finding, the problem
we face is that we still have no means of determining with any
accuracy how many eggs a female has and precisely how long that
supply will last.
The long-term goal of our research, as well as many others
in the field, is to fully understand the relationship between egg
number and fertility to enable the development of accurate
ovarian reserve tests that could be used to advise women about
their future fertility.
In the meantime, delayed child birth remains a risky business.
Karla Hutt is a Senior Research Fellow at the Department of Anatomy and Developmental
Biology, Monash University. Jock Findlay is a Distinguished Scientist at the Hudson Institute
of Medical Research.JAN/FEB 2016|| 19WavebreakmediaMicro/Adobe