Penteado Sandra H W, Teodorov Elizabeth, Kirsten Thiago B, Eluf Bianca P, Reis-Silva Thiago M, Acenjo Michelli K, de Melo Rafael C, Suffredini Ivana B, Bernardi Maria M
Graduate Program of Environmental and Experimental Pathology and Graduate Program Dentistry, Paulista University, UNIP, Rua Dr. Bacelar, 1212, São Paulo, SP, Brazil.
Mathematics, Computing and Cognition Center, Federal University of ABC, Av. dos Estados, 5001, Santo André 09210-971, SP, Brazil.
Eur J Pharmacol. 2014 Sep 5;738:342-51. doi: 10.1016/j.ejphar.2014.05.058. Epub 2014 Jun 11.
The present study analyzed the transgenerational effects of lipopolysaccharide (LPS; 100 μg/kg) administration on gestational day 18 (GD18) of parental generation on maternal-pups interaction of F1 and F2 generations. Also the long term behavioral effects were observed in male of F2 generation. In F1 generation, the reproductive performance, maternal behavior, maternal aggressive behavior, and general activity in the open field in adulthood were analyzed. In F2 generation, body weight at birth and at weaning, nest odor preference, and general activity in the open field and elevated plus maze in adulthood were assessed. Compared to controls, results showed that in the F1 generation, prenatal LPS exposure (1) increased the latency to full maternal behavior, but all of the females grouped the pups and presented full maternal behavior, (2) reduced the total time boxing and fighting, increased the frequency of retrieving the pups, and increased the number of bites, and (3) did not affect reproductive performance or general activity. In F2 generation, compared with controls, the LPS group exhibited (1) a decrease in body weight at weaning, (2) a decrease in nest odor preference, (3) a decrease in the percentage of time spent in the open arms, a decrease in the percentage of time spent in the center, and an increase in the time spent in the closed arms in the elevated plus maze, and (Huang et al.) no affect behavior in the open field. Prenatal LPS exposure improved maternal care in the F1 generation with regard to nursing and pup survival but did not improve the motivational parameters of maternal behavior likely because of a reduction of maternal stimulation by the pups. In the F2 generation, the reduction of nest odor preference in the pups suggests a less maternal recognition. In adulthood, these rats exhibited increased anxiety-like behavior. These data did not result from motor alterations because rats in both the F1 and F2 generations did not show alterations in open field behavior. This transfer of information across generations likely occurred through nongenetic means because the endotoxin was administered at the end of pregnancy. These results may have implications for clinical therapeutics in human disorders and evolution.
本研究分析了亲代在妊娠第18天（GD18）给予脂多糖（LPS；100μg/kg）对F1和F2代母鼠与幼崽互动的跨代影响。同时观察了F2代雄性的长期行为影响。在F1代中，分析了成年后的生殖性能、母性行为、母性攻击行为和旷场中的一般活动。在F2代中，评估了出生时和断奶时的体重、对窝气味的偏好以及成年后在旷场和高架十字迷宫中的一般活动。与对照组相比，结果显示在F1代中，产前LPS暴露（1）增加了完全母性行为的潜伏期，但所有雌性都将幼崽聚集在一起并表现出完全的母性行为，（2）减少了拳击和打斗的总时间，增加了找回幼崽的频率，并增加了咬伤次数，（3）对生殖性能或一般活动没有影响。在F2代中，与对照组相比，LPS组表现出（1）断奶时体重下降，（2）对窝气味的偏好降低，（3）在高架十字迷宫中，在开放臂中花费的时间百分比降低，在中心花费的时间百分比降低，在封闭臂中花费的时间增加，并且（黄等人）在旷场中对行为没有影响。产前LPS暴露改善了F1代在护理和幼崽存活方面的母性关怀，但可能由于幼崽对母性刺激的减少而没有改善母性行为的动机参数。在F2代中，幼崽对窝气味偏好的降低表明母性识别减少。在成年期，这些大鼠表现出焦虑样行为增加。这些数据并非由运动改变导致，因为F1和F2代的大鼠在旷场行为中均未表现出改变。这种跨代信息传递可能是通过非遗传方式发生的，因为内毒素是在妊娠末期给予的。这些结果可能对人类疾病的临床治疗和进化具有启示意义。
