[Dioxin-l] Effects of Polychlorinated Biphenyls on the Uterus

[Joseph R Parrish Jr]

SBRP "Research Brief" - Number 62

Title:  Understanding the Effects of Polychlorinated Biphenyls on the
Uterus

Regulation of uterine contractility is vital to successful reproduction.
During a full-term pregnancy, the uterus remains relatively inactive from=

conception until the initiation of labor -- a period of about 280 days fo=
r
humans.  As the time of delivery approaches, the uterus becomes highly
active with muscular contractions that increase in frequency and intensit=
y
until the fetus is forced out of the womb.  =


Fine-tuned control of uterine contractions is imperative not only for an
effective labor at the end of pregnancy, but also for preventing prematur=
e
labor.  However, for reasons that are poorly understood, the regulation o=
f
uterine contractions appears to be susceptible to interference by certain=

environmental contaminants.    =


Some studies suggest that polychlorinated biphenyls (PCBs), a group of
widespread, persistent environmental contaminants, may disrupt the natura=
l
termination of pregnancy by stimulating premature uterine contractions.
Both
PCB mixtures and individual congeners can stimulate contractions in
isolated
segments of uterus.   Yet the cellular and molecular events underlying th=
is
form of reproductive toxicity are relatively unknown.  =


Researchers at the University of Michigan -- a partner in the Michigan
State
University Superfund Basic Research Program -- recently elucidated a
possible mechanism for PCB-induced uterine contractions.  In a series of
experiments they discovered that the PCB mixture Aroclor 1242 can affect
several cellular events known to be involved in the development of
contractions in uterine muscle cells.  =


In one set of studies, Aroclor 1242 increased levels of the cellular
messenger arachidonic acid in cultured uterine muscle cells.  Enzyme
inhibition experiments revealed that this activity was mediated by an
enzyme
known as phospholipase A2.  Thus, the Aroclor 1242-induced release of
arachidonic acid likely occurred through activation of phospholipid cell
signaling pathways. Other experiments showed that Aroclor 1242 both
increased the influx of intracellular calcium and activated
voltage-operated
calcium channels in uterine muscle cells, a significant finding because
calcium is an essential stimulus for initiating uterine muscular
contractions.  Based on these findings, the scientists report "it is
possible that arachidonic acid liberated by Aroclor 1242 activates
voltage-operated calcium channels of [uterine muscle cells] and thus
stimulates uterine muscle contraction." =


PCBs have been associated with spontaneous abortion and shortened gestati=
on
length in women, wildlife and laboratory animals exposed to these
industrial
chemicals.  Because premature birth is a considerable health problem in
this
country -- it accounts for 75% of newborn deaths not related to
malformations -- it is important to determine how and to what extent PCBs=

may disrupt normal uterine functioning .  The mechanistic understanding
acquired in these studies is providing much needed insight into
reproductive
risks that may arise from PCB exposures.  =

_______________________________________________________________

For more information please contact:    =


Rita Loch-Caruso, Ph.D.
Toxicology Program =

Department of Environmental & Industrial Health
University of Michigan
1420 Washington Heights
Ann Arbor, MI  48109
Phone: (734) 936-1256
Email: rlc@umich.edu

To learn more about this research please refer to the following sources: =


Bae, J., M. Peters-Golden, and R. Loch-Caruso. 1999. Stimulation of
pregnant
rat uterine contraction by the polychlorinated biphenyl (PCB) mixture
Aroclor 1242 may be mediated by arachidonic acid release through activati=
on
of phospholipase A2 enzymes. J Pharmacol Exp Ther 289: 1112-1120.

Bae, J., E.L. Stuenkel, R. Loch-Caruso. 1999.  Stimulation of oscillatory=

uterine contraction by the PCB mixture aroclor 1242 may involve increased=

[Ca2+](i) through voltage-operated calcium channels. Toxicol Appl Pharm
155:
(3) 261-272.

______________________________________________________________

As always, your feedback is welcomed.

Beth Anderson
Program Analyst
Superfund Basic Research Program
National Institute of Environmental Health Sciences
tainer@niehs.nih.gov
-