Programa de Pós-Graduação em Biociências Aplicadas à Saude, Universidade Federal de Alfenas (Unifal-MG), Alfenas, Brazil; Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, Brazil.
Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, Brazil.
Life Sci. 2021 Jul 15;277:119611. doi: 10.1016/j.lfs.2021.119611. Epub 2021 May 10.
We assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size.
To reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28-32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting.
Our data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring.
This study alerts the public about the negative consequences of maternal overweight in the descendants.
通过减少窝仔数，评估母体超重对未成熟雄性和雌性仔鼠行为神经发育的影响。
为了减少 Wistar 大鼠的窝仔数，将第 0 代（G0）仔鼠中剔除 12 只（6 雄 6 雌：正常窝仔，NL-G1）或 4 只（2 雄 2 雌：小窝仔，SL-G1）。在 G1 孕鼠中，超重的特征为母体行为和运动活性的评估。在 G1 仔鼠中，我们在出生后第 5 天（PND5）量化了其高频发声；在第 13 天的归巢行为测试中评估了嗅觉辨别能力；在 PND28-32（未成熟年龄）时，我们进行了以下测试：社会玩耍行为、洞板、物体识别和旷场。实验结束时，解剖海马体和前额叶皮质，通过 Western blot 定量突触素蛋白。
我们的数据表明，减少窝仔数能够诱导母体超重，而不改变仔鼠超重相关参数。SL-G2 仔鼠表现出早期社会交流、嗅觉辨别、社会玩耍行为和物体探索能力受损，同时还增加了重复和刻板运动。来自减少窝仔数的母鼠的仔鼠海马体和前额叶皮质中的突触素蛋白水平也发生了变化。总之，由窝仔减少引起的母体超重会损害行为神经发育，导致仔鼠出现类似自闭症的症状。
本研究提醒公众关注母体超重对后代的负面影响。
