cancer (http://tinyurl.com/p3qw82p) and high-grade prostate
cancer (http://tinyurl.com/ob7qcmj).
Clearly this lack of definitive causation deserves intensive
study, and provides a compelling argument for the collection
of a detailed medical history at the time of infertility assess-
ment. Such data should be integrated with long-term follow-
up of outcomes and data linkage, as occurs in Scandinavia.
There are two possible explanations for the link between
male infertility and earlier death. These explanations are linked
to the complex and sensitive nature of sperm production and
are equivalent to the clinical distinctions of primary and
secondary testicular failure.
In primary cases, the origin of the infertility is in the testis,
where sperm production occurs. Spermatogenesis is a complex
process requiring the coordinated expression of many thou-
sands of individual genes to produce a cell, the sperm, that is ulti-
mately capable of both motility and fertility.
Spermatogenesis involves three major phases:- the continuous replication of a stem cell population;
- the mixing and halving of the genetic complement during
meiosis; and - a remarkable transformation wherein round spermatid cells
are transformed into the highly specialised and streamlined
cells we all recognise as sperm.
Spermatogenesis occurs at a frenetic pace across a male’s
adult life, leading to a mind-boggling production rate of 1000
sperm per second. To achieve this,
many pathways involved in sper-
matogenesis are running at “full
throttle”. If there is a problem
with an individual gene required
for sperm production, or a
pathway is impacted by an envi-
ronmental insult, sperm produc-
tion drops off and/or sperm
quality is compromised.
Importantly, however, many of
these pathways are conserved in
other parts of the body, but only
come into play at times of biolog-
ical stress. Notable examples
include DNA repair pathways that
are absolutely essential for male fertility but also exist to protect
the rest of the body against mutations and the development of
cancers.
Indeed, spermatogenesis has been a fantastic model system
to define pathways of fundamental importance to human health,
including the first discovery of stem cells, numerous aspects of
DNA repair pathways, and many aspects of the epigenetic path-
ways that are gaining such attention recently because of their
potential to transmit “poor health” across generations.
The second potential link between male infertility and
mortality is what is clinically referred to as secondary testic-
ular failure. Simplistically, this is when ill health in another
part of the body compromises sperm output. A classic example
is when structural or functional defects in the hypothalamo-
pituitary axis lead to the shutting down of sperm production,
but many more diverse causes exist including obesity, viral infec-
tions and environmental pollution. Spermatogenesis is remark-
ably sensitive.
Regardless of the cause of infertility, the link between male
fertility and long-term health offers an opportunity for early
intervention. If we as a research community are able to flesh
out the links between particular types of male infertility and
health, the presentation of a man at an infertility clinic will
offer the opportunity to not only provide him and his partner
with the children they clearly desire, but it will be an opportunity
to predict potentially more deadly and expressive disease at a
younger and more treatable age.
The first step in this worthy pathway would be the broad
acceptance that male infertility is a both common and serious
disease that is deserving of equal importance to some of the
more high profile diseases. It should be discussed openly, with
semen analysis a standard part of any male health workup.
Moira O’Bryan is Head of the Development and Stem Cells program at the Biomedicine
Discovery Institute at Monash University. Rob McLachlan is the Director of Andrology Australia.22 | JAN/FEB 2016
Credit: Andrology Australia... low semen volume, sperm
concentration and count, and the
percentage of motile sperm within
an ejaculate was associated with
higher risk of early death.