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The present study was planned to investigate the
impact of CIH on female fertility and evaluate the
adaptogenic activity of L-arginine supplementation and its
anti-stress effect on female fertility.
The study was performed on 48 adult female albino rats,
divided into the following groups:
group I: Control group (n=16), rats were housed (4
rats/cage) in room air. Also rats received distilled water
(the solvent of L-arginine), 5 days/week for 12 weeks by
group II: Hypoxic group (n=16), rats were subjected to
hypoxia for 8 hours/day, 5 days/week for 12 weeks.
Also rats received distilled water (the solvent of Larginine) 30 min prior to exposure to hypoxia, 5
days/week for 12 weeks by oral gavage.
group III: Hypoxic-supplemented group (n=16), rats
were supplemented with L-arginine by oral gavage in a
dose of 100 mg/kg body weight 30 min prior to
exposure to hypoxia, 5 days/week for 12 weeks. All the studied groups were subjected to:
Body weight measurement every two weeks for 12
Determination of phases of estrous cycle by vaginal
Ovarian weight measurement and determination of
Measurement of haematocrit value.
Determination of plasma levels of progesterone and
Evaluation of oxidative stress by measuring MDA
level in the ovarian tissue.
Evaluation of anti-oxidative capacity by measuring
CAT enzyme activity in the ovarian tissue.
Evaluation of apoptosis at germinal cell level by
measuring the caspase-3 enzyme level in the ovarian
Examination of histopathological changes in the
The study revealed that the exposure to CIH
significantly resulted in increased HV, decreased body
weight and increased ovarian tissue MDA level that was
associated with decreased CAT enzyme activity. Asignificant increase in LH plasma levels was observed in
both rats with regular cycle and those with irregular cycle.
Also there was a higher rate of mortality and increased
incidence of rats with irregular cycle among hypoxic group
compared to the control group.
Histopathological examination of ovarian sections
from rats exposed to CIH showed alterations and changes
indicating hypoxic stress compared to their matching
controls. At the same time, the immunohistochemical study
showed an increase in the expression of caspase-3 enzyme
in ovarian tissue of the hypoxic group.
On the other hand pretreatment with L-arginine
showed an improvement in most of the parameters
investigated in this study compared to the hypoxic group as
shown by the significant increase in body weight, decrease
in MDA level, decrease in LH hormone levels in addition
to lower incidence of cycle irregularity and rate of
mortality. There was also improvement in histopathological
picture as well as lowered caspase-3 enzyme expression in
the ovarian tissue.
This improvement could be explained by the role of
L-arginine, the endogenous precursor of NO, as antioxidant and anti-apoptotic in addition to its anti-inflammatory