Premature menopause
Premature menopause or premature ovarian failure (POF), is defined as
menopause occurring in women under the age of 40. POF is a common disorder, and
occurs in about 1-2% of women, in some as early as their late teens and twenties. The
cause of most cases of POF is unknown. A number of families exist where there is
an inherited predisposition to POF that would suggest that there is an inherited
defective gene. We wish to determine the molecular defects in families that have
led to the development of premature menopause. We have previously found mutations
in two genes in woman with POF, in the inhibin alpha gene, and the FOXL2 gene.
We are also looking at other genes that are likely to be strong candidates for the
development of POF. Ascertainment of the molecular basis of POF would provide a
better understanding of the reproductive processes involved. It would form the basis
for a genetic test for other family members at risk of developing POF. Affected
women could then make informed reproductive choices, in particular with respect
to the timing of child-bearing. The most immediate concern for women with POF are
the menopausal symptoms they experience, coupled with the psychological implications
of these symptoms. However, longterm there are concerns about a greater risk of
osteoporosis and cardiovascular disease. Eventually, an understanding of the genetic
defect may allow us to return fertility to some of these women by replacing the
defective molecule.
Dr Shelling set up the New Zealand Premature Menopause Support Group and continues to be involved in
the group. He is also a patron of the UK based Daisy Network Premature Menopause Support Group.
New
Zealand Premature Menopause Support Group
Antisperm antibodies and male
infertility
Sperm antibodies can be found in up to 25% of infertile couples but are also found
in approximately 10% of normal fertile couples. Thus, it is difficult to determine
the contribution that these antibodies make to infertility. Part of the reason for
this confusion is the poor quality of existing diagnostic tests for sperm antibodies.
In collaboration with Dr Larry Chamley (Department of Obstetrics and Gynaecology)
we have recently identified SPRASA, which is a highly conserved sperm protein that
is the target of antisperm antibodies from infertile men.
We believe SPRASA has an essential role in fertilisation that is blocked by some
antisperm antibodies. The function of SPRASA is unknown but its localisation on
sperm, as well as similarities to other known proteins suggests that SPRASA may
be involved in the binding of sperm to oocytes. We are focused on identifying the
function of SPRASA in fertility. This will allow us to determine whether SPRASA
may be a target for the manipulation of reproductive function for the purposes of
contraception or fertility enhancement.
