Brain-synthesized oestrogens regulate cortical migration in a sexually divergent manner.
Brain-synthesized oestrogens regulate cortical migration in a sexually divergent manner.
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大脑合成的雌激素以性别不同的方式调节皮质迁移。
DOI：
10.1111/ejn.14755
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sellers KJ
中科院分区：
文献类型：
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作者：
Sellers KJ
雌激素在大脑发育中发挥着重要作用，它们参与控制各种细胞过程。多项证据表明雌激素可以在大脑内局部合成。研究表明，芳香酶（负责将雄激素转化为雌激素的酶）在男性和女性皮质的早期发育过程中表达。此外，已在多个物种的胎儿脑组织中检测到 17β-雌二醇。 17β-雌二醇调节神经祖细胞增殖以及早期神经元形态的发育。然而，本地来源的雌激素在调节皮质迁移方面发挥什么作用以及这些作用在男性和女性中是否相同尚不清楚。在这里，我们研究了胚胎第 14.5 天 (E) 和出生后第 0 天 (P0) 之间编码芳香酶的 Cyp19a1 的敲低表达对皮质内神经迁移的影响。芳香酶在两性小鼠的发育中皮层中都有表达，但雄性小鼠的水平显着高于雌性小鼠。在基础条件下，雄性和雌性小鼠的皮质迁移没有观察到明显差异。然而，Cyp19a1 的敲除导致 P0 雄性小鼠皮质板内细胞的增加，同时室下区/室区的细胞减少。有趣的是，在女性中观察到相反的效果，迁移到皮质板的细胞显着减少。总之，这些发现表明，脑源性雌激素通过男性和女性的不同机制调节径向迁移。
Oestrogens play an important role in brain development where they have been implicated in controlling various cellular processes. Several lines of evidence have been presented showing that oestrogens can be synthesized locally within the brain. Studies have demonstrated that aromatase, the enzyme responsible for the conversion of androgens to oestrogens, is expressed during early development in both male and female cortices. Furthermore, 17β‐oestradiol has been measured in foetal brain tissue from multiple species. 17β‐oestradiol regulates neural progenitor proliferation as well as the development of early neuronal morphology. However, what role locally derived oestrogens play in regulating cortical migration and, moreover, whether these effects are the same in males and females are unknown. Here, we investigated the impact of knockdown expression ofCyp19a1, which encodes aromatase, between embryonic day (E) 14.5 and postnatal day 0 (P0) had on neural migration within the cortex. Aromatase was expressed in the developing cortex of both sexes, but at significantly higher levels in male than female mice. Under basal conditions, no obvious differences in cortical migration between male and female mice were observed. However, knockdown ofCyp19a1resulted in an increase in cells within the cortical plate, and a concurrent decrease in the subventricular zone/ventricular zone in P0 male mice. Interestingly, the opposite effect was observed in females, who displayed a significant reduction in cells migrating to the cortical plate. Together, these findings indicate that brain‐derived oestrogens regulate radial migration through distinct mechanisms in males and females.