الفهرس 
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Abstract
The present study was an endeavor for profound exploration of the beneficial effects of melatonin (MLT) against Bisphenol A (BPA) exposure in pregnant rats and the resulted influences on their first generation. Attention was specified for reproductive capacities of male and female offsprings at adulthood in addition to their metabolic performance especially the thyroid activities.
For that purpose, forty adult virgin female albino rats plus 10 adult male rats were equally divided into 5 groups (each group included 8 adult female rats plus 2 adult male rats for breeding, where all treatments were applied only for the pregnant female rats): 1) group I (control group; n=10), 2) group II (Low dose BPA; n=10, pregnant female rats received a daily dose of 25 µg BPA / kg B.w.t.), 3) group III (Low dose BPA + 10 mg MLT /kg B.w.t./day; n=10), 4) group IV (High dose BPA “250 µg BPA / kg B.w.t/ day”; n=10) and 5) group V (High dose BPA + MLT; n=10). All pregnant female rats within each group received their specific treatment with subcutaneous injection using fibroglass needle starting from the fourth day of pregnancy till full term.
After delivery, 20 albino rats (10 males and 10 females) were selected from the litters of control and both MLT groups. In both low and high BPA doses groups, because lower pregnancy rates, 12 albino rats (6 males and 6 females) were selected. Thus, the work was classified into 2 experiments: 1) experiment I for male offsprings and 2) experiment II for female offsprings. All selected rats were weighted (Initial weight) and reared under the same environmental conditions till the 60th day after birth (i.e. after the age of puberty). Then, on the 60th day, the offsprings of each group in each experiment were weighed (Final weight), subjected to blood collection and were sacrificed for tissue samples collection.
At first, the pregnancy rates in all groups were recorded and compared among groups.
In Experiment I (male offsprings), body weight gains and testicular weights were recorded. Moreover, serum analyses of Testosterone (T), triiodotyrosine (T3), malondialdehyde (MDA) and total antioxidant activities (TAC) were assessed. Also, epididymal semen were evaluated and histopathology for testes and prostate glands was demonstrated.
In experiment II (female offsprings), body weight gains, ovarian and uterine weights, estrus cycles regularity and serum levels of estrogen, T3, MDA and TAC were reported. Also, histopathology of ovarian and uterine tissues was illustrated.
Analysis of data revealed that:
It was noticed that number of pregnant rats were decreased markedly in both BPA groups in comparison to control group. In addition, the declined number of pregnancies were recovered significantly after MLT co-administration.
In experiment I (male offsprings), results of the current study indicated that neither small nor large dose of BPA had negative effects (P>0.05) on the body weight gain and testicular weights. In addition, both doses of BPA caused significant reduction of the serum levels of T of male neonates (F1) on the 60th day after birth in comparison to control group (P < 0.05). Also, it was clear that serum levels of T3 were decreased significantly (P<0.05) with 25 µg BPA but not with 250 µg BPA administration in comparison to control group. Moreover, serum level of TAC was reduced significantly whereas that of MDA was elevated markedly in both small and high BPA doses groups when compared to the control one (P<0.05). Sperm concentration was reduced significantly in 25 µg BPA - exposed rats in comparison to control ones. Also, prenatal exposure for low and high doses of BPA increased the percentage of second abnormalities in comparison to control group (P < 0.05). Although, the percentages of primary abnormalities were similar in all treatments. Furthermore, histopathological findings displayed that prenatal BPA administration either at low or high dose induced marked degenerative changes in both testicular and prostatic tissues.
On the other side, MLT co-administration with both doses of BPA didn’t induce any effects (P>0.05) on the body weight gain and testicular weights. However, prenatal MLT co-administration was found to have positive effects against BPA exposure either at low or high dose as it convalesced significantly the lower levels of T toward control values (P < 0.05). Also, treatment with 250 µg BPA + MLT increased significantly the serum levels of T3 when compared to either 250 µg BPA or control groups (P < 0.05). However, BPA 25 µg + MLT enhanced significantly the serum level of T3 greater than 25 µg BPA group and amended it to the control values. In addition, the oxidative stress provoked by small and high BPA doses administration was ameliorated impressively after MLT co-administration (P < 0.05). Moreover, MLT induced a significant increase in sperm concentration and marked decrease of the percentage of second abnormalities in comparison to control and BPA groups (P < 0.05). The histopathological findings illustrated that, MLT co-administration succeeded markedly in relieving the deteriorating changes of testes and prostate glands observed with both doses of BPA.
In experiment II (female offsprings), the data of the current study clarified that neither small nor large dose of BPA had negative effects on the Body weight gain and uterine weights of female offsprings when compared with control group (P>0.05). However, the ovarian weights were increased significantly (P < 0.05) with 250 µg BPA but slightly with 25 µg BPA when compared with control group. Moreover, both doses of BPA reduced significantly the percentages of females with regular cyclicity. In addition, there was a significant increase in serum level of estrogen hormone at estrus phase with administration of both BPA doses when compared to control group (P < 0.05). In addition, serum T3 were decreased significantly in both BPA groups in comparison to the control group (P < 0.001). Further, serum levels of MDA were elevated and that of TAC were reduced significantly with either small or high dose of BPA when compared to control one (P < 0.05). Histopathological evaluation revealed that small and high doses of BPA induced many degenerative changes in the ovarian and uterine tissues.
On the contrary, values of body weight gain, ovarian and uterine weights were similar to control ones after MLT co-administration. Moreover, the percentages of rats with regular cyclicity have been improved noticeably after MLT co- administration. Co-administration of MLT with both doses of BPA succeeded in significant modulation of the elevated serum levels of estrogen and kept them near the control values when compared with BPA groups (P < 0.05). In addition, MLT co-administration was potent enough to reverse the action of BPA and exhibited significant improvement in the levels of T3 greater than both BPA groups (P < 0.001) but didn’t recover them to the control level. MLT achieved significant improvement in the serum level of TAC and MDA when compared with BPA - exposed groups. Furthermore, MLT co–administration ameliorated greatly the deteriorating effects of BPA on both ovarian and uterine tissues.
from the findings of the current study, it could be concluded that MLT might be considered as an optimistic treatment against in utero exposure of pregnant rats for either low or high BPA dose on the reproductive capacity and thyroid activity of their male and female offsprings.