Seminal Plasma Lipocalin-Type Prostaglandin D Synthase: A
Potential New Marker for the Diagnosis of Obstructive Azoospermia
Samy M. Heshmat, J. Brendan Mullen, Keith A. Jarvi, Antoninus Soosaipillai,
Eleftherios P. Diamandis, Robert J. Hamilton and Kirk C. Lo*,†
From the Departments of Surgery (Division of Urology) (SMH, JBM, KAJ, EPD, RJH, KCL) and Pathology and Laboratory Medicine
(JBM, KAJ, AS, EPD), Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
Purpose: We examined the relationship between L-PGDS (lipocalin-type prostaglandin D synthase) levels in seminal plasma
and the presence or absence of obstruction in the male seminal tract.
Materials and Methods: Semen samples were collected and analyzed from 1) 10 patients with normal semen parameters,
2) 9 with obstructive azoospermia, 3) 20 after vasectomy and 4) 14 with nonobstructive azoospermia. Seminal L-PGDS was
measured using an enzyme-linked immunosorbent assay technique.
Results: We found that seminal plasma L-PGDS in the groups with obstruction was significantly lower than in any of the
other groups (p 0.001). Using a cutoff of 100 g/l all men with obstructive azoospermia had L-PGDS less than 100 g/l, while
none with normal sperm parameters did. Men with nonobstructive azoospermia had less homogeneity of L-PGDS levels,
including 29.6% with L-PGDS more than 100 g/l.
Conclusions: Our results suggest that seminal L-PGDS level can potentially be a biomarker for assessing patency in the
seminal tract in men with azoospermia. In men with azoospermia and high seminal L-PGDS (more than 100 g/l) the
diagnosis of nonobstructive azoospermia can be potentially made without biopsy. Our study shows that using semen L-PGDS
levels provides a diagnosis of nonobstructive azoospermia in almost 30% of these men.
Key Words: testis; infertility, male; prostaglandin R2 D-isomerase; azoospermia; semen
I
nfertility is a common condition, affecting up to 15% of
couples.
1
Male factor is implicated in approximately
50% of the cases.
2
Azoospermia is a clinical presentation
characterized by the absence of any spermatogenic elements
in at least 2 semen analyses. It is diagnosed in up to 5% of
men presenting for infertility investigations.
3
The etiology of azoospermia can be classified into 2 types,
including OA secondary to blockage in the sperm transport
and NOA, which is due to primary testicular failure or
secondary to hypothalamic-pituitary diseases. Patients with
OA are usually characterized by having normal testicular
volume and normal gonadotropin concentrations. However,
about 29% of men with normal FSH and normal testicular
size have defective spermatogenesis on testicular biopsy.
2
Therefore, the definitive diagnosis of obstructive azoosper-
mia can only be made by performing testicular biopsy, which
is an invasive procedure.
A biomarker that can be easily obtained from the patient
such as seminal fluid would be a less invasive alternative to
differentiate OA and NOA. We have previously studied a
number of seminal plasma proteins, such as L-PGDS,
prostate specific antigen, PepC, BRCA1-LIP and IGFBP-3.
4
Of them L-PGDS, which is mainly produced by the Sertoli’s
cells in the testis, appears to be the most promising candi-
date. L-PGDS is a secretory glycoprotein with a molecular
mass of 26 kDa. This protein was first described under the
name -trace by Clausen as a major protein present in
cerebrospinal fluid.
5
It belongs to the lipocalin superfamily,
which includes an array of extracellular transport proteins
showing high binding affinity for specific cell receptors and
small hydrophobic ligands.
6
It is now well-known that
L-PGDS is abundant in compartments beyond blood-tissue
barriers, such as in the cerebrospinal fluid,
7
aqueous hu-
mor,
8
amniotic fluid
9
and seminal fluid.
10
Its concentrations
in these body fluids is useful for diagnosing neurological
disorders,
11
and cardiovascular,
12
renal
13
and lung
14
dis-
eases. The role of L-PGDS in male reproduction is still
unclear. Most investigators believe that the major function
of L-PGDS in male fertility would be related to its capability
of providing thyroid hormones and retinoids beyond the
blood-testis barrier to developing germ cells in the seminif-
erous tubules and to maturing spermatozoa in the
epididymis.
15
Previous studies have localized L-PGDS by immunohis-
tochemical studies to the testis and epididymis, and the
epithelium of the prostate gland with the most abundant
expression in the testis, specifically in Sertoli’s cells.
4,16
Other studies have also demonstrated L-PDGS expression
in Leydig cells.
16
L-PGDS is secreted into seminal fluid,
where its concentration represents approximately 0.1% of
total secreted proteins.
16
We hypothesized that L-PGDS in
Submitted for publication July 9, 2007.
Study received approval from the Mount Sinai Hospital Research
and Ethics Board.
* Correspondence: Division of Urology, Department of Surgery,
Mount Sinai Hospital, University of Toronto, Murray Koffler Uro-
logic Wellness Centre, 60 Murray St., 6th Floor, Toronto, Ontario,
Canada, M5G 1X5 (telephone: 416-586-4613; FAX: 416-586-8354;
e-mail: klo@mtsinai.on.ca).
† Financial interest and/or other relationship with Bayer Canada.
0022-5347/08/1793-1077/0 Vol. 179, 1077-1080, March 2008
THE JOURNAL OF UROLOGY
®
Printed in U.S.A.
Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.10.070
1077