We have previously reported that prenatal alcohol exposure (PAE) in the 2nd trimester-equivalent of gestation is associated with increased N-methyl-d-aspartate (NMDA)-induced generalized tonic-clonic seizures (GTCSs) prevalence in postpartum developing rats. Whether the 1st trimester-equivalent of gestation is also a vulnerable period for developing GTCSs following PAE is unknown. Here, we investigated the effects of a single episode of PAE at embryonic day 8 (E8, in the 1st trimester-equivalent) or E18 (in the 2nd trimester-equivalent) on NMDA-induced seizures in developing rats at postnatal day 7 (P7, the equivalent of preterm newborns) and P15 (the equivalent of term infants). Pregnant Sprague-Dawley rats were given a single oral dose of ethanol (5 g/kg body weight) at E8 or E18 and the postpartum rats were tested for the susceptibility to NMDA-induced seizures at either P7 or P15. NMDA-induced seizures consisted of wild running-like behavior (WRLB), flexion seizures (FSs), clonic seizures (CSs), GTCSs, and tonic seizures (TSs); these seizures were observed in both control-treated and PAE-treated, male and female, P7 and P15 rats. Quantification reveals that the overall prevalence of CSs, GTCSs and TSs occurrence were significantly increased in the E18-PAE group compared to E8-PAE group, adjusting for sex and postnatal day. Furthermore, the overall prevalence of FSs and TSs occurrence was significantly increased in PAE-treated males compared to females, adjusting for embryonic stage and postnatal day. The overall prevalence of WRLB and FSs occurrence was also increased in PAE-P7 rats compared to PAE-P15 rats, adjusting for sex and embryonic stage. We conclude that the susceptibility to develop GTCSs was higher when PAE occurred in the 2nd rather than in the 1st trimester-equivalent of gestation.

中文翻译：

---

孕中期的产前酒精暴露会增加发育中大鼠的癫痫发作敏感性。

我们先前曾报道过，妊娠第二个孕期中的产前酒精暴露（PAE）与产后发育中大鼠N-甲基-d-天冬氨酸（NMDA）引起的全身性强直阵挛性癫痫发作（GTCSs）患病率增加有关。尚不清楚妊娠前三个月的妊娠是否也是PAE后发展GTCS的脆弱时期。在这里，我们调查了在出生后第7天，胚胎发育第8天（E8，在孕中期的当量）或E18（在孕中期，当量的第二代）单次PAE对NMDA诱发的癫痫发作的影响（P7） ，相当于早产儿）和P15（相当于早产儿）。在E8或E18给予怀孕的Sprague-Dawley大鼠单次口服乙醇（5 g / kg体重），并在P7或P15对产后大鼠进行NMDA诱发的癫痫发作的敏感性测试。NMDA诱发的癫痫发作包括野外奔跑行为（WRLB），屈曲性癫痫发作（FSs），阵挛性癫痫发作（CSs），GTCS和滋补性癫痫发作（TSs）。在对照和PAE处理的雄性和雌性P7和P15大鼠中均观察到了这些癫痫发作。定量分析显示，与E8-PAE组相比，E18-PAE组CS，GTCS和TS发生的总体患病率显着增加，并根据性别和产后天数进行了调整。此外，与胚胎期相比，PAE治疗的雄性与雌性相比，FS和TS发生的总体患病率显着增加。与PAE-P15大鼠相比，PAE-P7大鼠的WRLB和FSs发生的总体患病率也有所增加，并调整了性别和胚胎阶段。我们得出的结论是，当PAE发生在妊娠的第2个月而不是妊娠的第3个月时，发生GTCS的敏感性更高。