| Objective:(1) To investigate whether the reference dose of BPA ingested chronically by male rats before conception would affect spatial memory and hippocampal acetylcholinesterase (AChE) in themselves and their adult offspring.(2) soy phytoestrogen genistein (GEN), a natural EDC, has a protective effect against cognitive decline and metabolic disease. To investigate the combinational effect of BPA and a high-fat diet (HFD) on male rats’ spatial memory performance and whether this could be mitigated by GEN.Methods:Part one:Twenty-two60days old male Wistar rats (F0) were randomly assigned to a control or BPA group (n=11, each), receiving corn oil vehicle or50μg/kg bw/day BPA in corn oil for10weeks before being mated with non-exposed females in estrus. After about two weeks from the mating, all F0rats were introduced to the Morris Water Maze (MWM) test for one week then were sacrificed for testing their hippocampal AChE activities and serum free BPA levels. Their offspring (F1) received no treatment until behavioral testing at the age of PND56for the MWM and hippocampal AChE by using the same methods as their fathers. Food intake and body weight of all animals were routinely recorded.Part two:Seventy-two sixty-day-old male Wistar rats were randomly fed either a control diet (CD) or HFD and also received daily oral doses of either0,50μg/kg bw/day BPA and/or0,10mg/kg bw/day GEN for20weeks. Their spatial memory functions were then assessed in the MWM.Results:Part one:(1) There was no significant difference between F0control and BPA male rats in daily food consumption and body weight.(2) There was no significant significant difference between F0control and BPA dams in daily food consumption and body weight.(3) There was no significant difference between control and BPA pups for sex ratio and litters’ weight. From postnatal day (PND)0to PND55, all male pups had more daily food consumption [F (9,324)=60.99, P<0.01] and higher body weight [F (9,324)=60.99, P<0.01] compared to the females in the same-treatment group. No difference was observed between different treatment groups within the same sex.(4) WMW in F0rats:BPA rats swam longer distance [F (1,20)=7.39, P=0.01] and spent more time [F (1,20)=5.88, P=0.03] with faster swimming velocity [F (1,20)=6.25, P=0.02] to find a hidden platform than did the control counterparts, they also made fewer platform contact accuracies [t(20)=4.57, P<0.01] and the duration was shorter in the platform quadrant [t (20)=4.41, P<0.01] relative to the controls.(5) Hippocampal AChE activities in F0rats:BPA group exhibited decreased AChE activity in the hippocampus relative to the controls [t (20) =2.71, P=0.01].(6) WMW in F1rats:F1offspring of both sexes from BPA fathers swam greater distance [F (1,36)=51.73, P<0.01] and needed more time [F (1,36)=25.07, P<0.01] in finding a hidden platform than did the control offspring. F1BPA females escaped significantly faster [F (1,18)=4.99, P=0.03], had less platform crossings (t(18)=3.71, P<0.01)and shorter duration [t(18)=2.78, P=0.01] in the target quadrant (P<0.05) than the same sex controls. A sex difference emerged in the form of a small but statistically significant male advantage among F1BPA offspring in the measures of platform crossing [t (18)=3.21, P<0.01] and duration in the target quadrant [t(18)=2.78, P=0.01](both BPA females<BPA males).(7) Hippocampal AChE activities in F1rats:A typical sex difference was confirmed in control but not BPA offspring (control female> control male, t (18)=2.42, P=0.02).(8) The serum level of free BPA was1.88±0.34ng/ml in F0control rats, and12.71±2.35ng/ml in F0BPA rats, which was within the normal range of humans.Part two:Among CD rats:BPA and BPA+GEN rats produced comparably larger swimming distance, longer latency and shorter duration in the target quadrant, while GEN rats did normal in these parameters (for swimming distance:F (3,32)=8.27, P <0.01, for latency:F (3,32)=5.88, P<0.01), and all of these treatment groups had higher swimming speed, when compared to control vehicle rats [F (3,32)=3.41, P=0.03]. All HFD rats showed equivalent larger swimming distance, longer latency while shorter duration in the target quadrant relative to control vehicle rats (all P<0.01). They also exhibited increased swimming velocity except in the case of GEN (both P=0.02).Conclusions:These data provide new evidence that paternal BPA exposure, at the reference dose, may induce spatial memory deficit not only in directly exposed fathers but also their unexposed offspring with transgenerational alterations in a sex-specific manner. HFD and BPA displayed similar potency to produce spatial memory deficits and higher swimming speed in adult male rats, without combinational effect; GEN alone had no effect on the response to BPA, but when co-supplemented with HFD, enhanced swimming activity more than memory. |
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