11 / 25
PCOS 2018
Journal of Clinical and Molecular Endocrinology
ISSN: 2572-5432
Page 39
June 07-08, 2018
London, UK
4
th
World Congress on
Polycystic Ovarian
Syndrome
P
olycystic ovary syndrome (PCOS) is the number one cause of
female infertility. Some mouse models are available to study
it. These models are generated by different methods (mainly via
administration of dihydrotestosterone) because its origin is not
fully understood. A genetic cause has not been confirmed yet. Via
insertional mutagenesis, we identified a new gene (
Gm10800
),
which when disrupted in mice appears to phenocopy human
PCOS. We are currently characterizing this transgenic mouse
model (G4), have validated it as a PCOS model, studying the link
between
Gm10800
and the observed phenotypes (obesity and
sub-fertility). The main features of this model are: 1. Obesity with
associated abnormalities such as glucose and insulin intolerance,
polyphagia, high leptin levels, and lipid deposition in the ovaries.
2. Sub-fertility associated with cysts in the ovaries, di-estrous
arrest, high percentage of non-viable oocytes, and high levels of
LH, estrogen and testosterone. The gene disrupted by transgenic
insertion (
Gm10800
) appears to be the mouse ortholog of a
human gene known as PIRO
(progranulin-induced receptor-like
gene during osteoclastogenesis)
. There is a single paper that
discusses this gene, suggesting a role for it in the formation of
osteoclasts. In accordance with this, our preliminary micro-CT
analyses of bone mass density show that transgenic mice have
greater bone mass than controls. Ongoing work is aimed at
determining how
Gm10800/PIRO
contributes to the observed
phenotypes. In conclusion, the G4 mouse model points to a direct
link between PCOS and a gene for the first time. It’s also the most
representative model of PCOS currently available. This makes it
an extremely valuable model to better understand the disease
and the mechanism of action of some existing medication for
it like metformin. It also gives us a precious chance to test new
drugs on this model like endoplasmic reticulum stress inhibitors
that are already in the drug market for other diseases, like TUDCA
(Tauroursodeoxycholic acid).
tefasiena@gmail.comG4, a new transgenic mouse model for polycystic ovaries
syndrome
Mostafa Esmael
UQAM, Canada
J Clin Mol Endocrinol 2018, Volume 3
DOI: 10.21767/2572-5432-C1-003