BACKGROUND Steroid sulfatase (STS) cleaves sulfate groups from steroid hormones; its expression/activity increases in late pregnancy and into the postpartum period. STS-deficient human and mouse mothers display elevated psychopathology and abnormal behaviour respectively; in mice, these effects can be partially normalised by antipsychotic (ziprasidone) administration. METHODOLOGY We compared brain gene expression in new mouse mothers administered the STS inhibitor 667-Coumate, or vehicle; significant changes were followed-up with pathway analysis and quantitative polymerase chain reaction (qPCR). Finally, the effects of combined 667-Coumate and ziprasidone administration on expression of the most robustly differentially-expressed genes were examined. RESULTS Surprisingly, no between-group gene expression changes were detected at a False Discovery Rate (FDR)-corrected p<0.1. 1,081 unique expression changes were detected at p<0.05, two top hits were verified by qPCR, and pathway analysis indicated enrichment of genes involved in olfactory transduction. The expression of Stoml3 and Cyp2g1 was unaffected by ziprasidone administration. CONCLUSIONS Postpartum behavioural abnormalities in STS-deficient mothers are likely to be the culmination of many small gene expression changes. Our data are consistent with the idea that olfactory function is key to maternal behaviour in mice, and suggest that aberrant expression of olfactory system genes may underlie abnormal maternal behaviour in STS-deficient women.

中文翻译：

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产后情绪障碍新型小鼠模型中的脑基因表达。

背景类固醇硫酸酯酶（STS）从类固醇激素中裂解硫酸基团；其表达/活性在妊娠晚期和产后期增加。缺乏STS的人类和小鼠母亲分别表现出较高的精神病理学和异常行为；在小鼠中，这些效应可以通过服用抗精神病药物（齐拉西酮）部分恢复正常。方法学 我们比较了给予 STS 抑制剂 667-Coumate 或媒介物的新小鼠母亲的大脑基因表达。通过途径分析和定量聚合酶链反应（qPCR）跟踪显着变化。最后，检查了 667-Coumate 和齐拉西酮联合给药对最稳健差异表达基因表达的影响。结果令人惊讶的是，在错误发现率 (FDR) 校正 p<0.1 下，没有检测到组间基因表达变化。在 p<0.05 下检测到 1,081 个独特的表达变化，通过 qPCR 验证了两个热门命中，通路分析表明参与嗅觉转导的基因富集。Stoml3和Cyp2g1的表达不受齐拉西酮给药的影响。结论 STS 缺陷母亲的产后行为异常可能是许多小基因表达变化的结果。我们的数据与嗅觉功能是小鼠母性行为关键的观点一致，并表明嗅觉系统基因的异常表达可能是 STS 缺陷女性母性行为异常的基础。