Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
Division of Health Sciences, Department of Medical Sciences, University of Guanajuato, Leon Campus, Leon, Gto., Mexico.
PLoS One. 2024 Mar 21;19(3):e0300141. doi: 10.1371/journal.pone.0300141. eCollection 2024.
Arachidonic acid (AA) is involved in inflammation and plays a role in growth and brain development in infants. We previously showed that exposure of mouse sires to AA for three consecutive generations induces a cumulative change in fatty acid (FA) involved in inflammation and an increase in body and liver weight in the offspring. Here, we tested the hypothesis that paternal AA exposure changes the progeny's behavioral response to a proinflammatory insult, and asked whether tissue-specific FA are associated with that response. Male BALB/c mice were supplemented daily with three doses of AA for 10 days and crossed to non-supplemented females (n = 3/dose). Two-month-old unsupplemented male and female offspring (n = 6/paternal AA dose) were exposed to Gram-negative bacteria-derived lipopolysaccharides (LPS) or saline control two hours prior to open field test (OFT) behavioral analysis and subsequent sacrifice. We probed for significant effects of paternal AA exposure on: OFT behaviors; individual FA content of blood, hypothalamus and hypothalamus-free brain; hypothalamic expression profile of genes related to inflammation (Tnfa, Il1b, Cox1, Cox2) and FA synthesis (Scd1, Elovl6). All parameters were affected by paternal AA supplementation in a sex-specific manner. Paternal AA primed the progeny for behavior associated with increased anxiety, with a marked sex dimorphism: high AA doses acted as surrogate of LPS in males, realigning a number of OFT behaviors that in females were differential between saline and LPS groups. Progeny hypothalamic Scd1, a FA metabolism enzyme with documented pro-inflammatory activity, showed a similar pattern of differential expression between saline and LPS groups at high paternal AA dose in females, that was blunted in males. Progeny FA generally were not affected by LPS, but displayed non-linear associations with paternal AA doses. In conclusion, we document that paternal exposure to AA exerts long-term behavioral and biochemical effects in the progeny in a sex-specific manner.
花生四烯酸（AA）参与炎症反应，并在婴儿的生长和大脑发育中发挥作用。我们之前的研究表明，雄性小鼠连续三代暴露于 AA 会导致参与炎症的脂肪酸（FA）发生累积性变化，并导致后代的体重和肝脏重量增加。在这里，我们检验了这样一种假设，即雄性亲代 AA 暴露会改变后代对促炎刺激的行为反应，并探讨组织特异性 FA 是否与这种反应相关。雄性 BALB/c 小鼠每天接受三剂 AA 补充 10 天，并与未补充的雌性小鼠交配（n = 3/剂量）。2 个月大的未补充雄性和雌性后代（n = 6/雄性亲代 AA 剂量）在进行开放式场测试（OFT）行为分析和随后的安乐死之前两小时接受革兰氏阴性细菌衍生的脂多糖（LPS）或盐水对照处理。我们探测了雄性亲代 AA 暴露对以下方面的显著影响：OFT 行为；血液、下丘脑和无下丘脑大脑的个体 FA 含量；与炎症相关的基因（Tnfa、Il1b、Cox1、Cox2）和 FA 合成（Scd1、Elovl6）在下丘脑的表达谱。所有参数均以性别特异性方式受到雄性亲代 AA 补充的影响。雄性亲代 AA 使后代产生与焦虑增加相关的行为，具有明显的性别二态性：高 AA 剂量在雄性中充当 LPS 的替代物，调整了一些 OFT 行为，而在雌性中，这些行为在 LPS 和盐水组之间存在差异。后代下丘脑 Scd1 是一种具有已知促炎活性的 FA 代谢酶，在雌性高雄性亲代 AA 剂量下，与 LPS 组之间表现出类似的差异表达模式，而在雄性中则减弱。后代 FA 通常不受 LPS 影响，但与雄性亲代 AA 剂量呈非线性关联。总之，我们证明了雄性亲代暴露于 AA 会以性别特异性方式对后代产生长期的行为和生化影响。
