Data from: Sex-dependent effects of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) on dendritic arborization of primary mouse neurons

Early life exposures to environmental contaminants are implicated in the
pathogenesis of many neurodevelopmental disorders (NDDs). These disorders
often display sex biases, but whether environmental neurotoxicants act in
a sex-dependent manner to modify neurodevelopment is largely unknown.
Since altered dendritic morphology is associated with many NDDs, we tested
the hypothesis that male and female primary mouse neurons are
differentially susceptible to the dendrite promoting activity of
2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical
neuron-glia co-cultures were exposed to vehicle (0.1% DMSO) or PCB 95 (100
fM - 1 μM) from day in vitro 7-9. As determined by Sholl analysis, PCB 95
enhanced dendritic growth in female but not male hippocampal and cortical
neurons. In contrast, both male and female neurons responded to
bicuculline with increased dendritic complexity. Detailed morphometric
analyses confirmed that PCB 95 effects on the number and length of primary
and non-primary dendrites varied depending on sex, brain region and PCB
concentration, and that female neurons responded more consistently with
increased dendritic growth and at lower concentrations of PCB 95 than
their male counterparts. Exposure to PCB 95 did not alter cell viability
or the ratio of neurons to glia in cultures of either sex. These results
demonstrate that cultured female mouse hippocampal and cortical neurons
are more sensitive than male neurons to the dendrite promoting activity of
PCB 95, and suggest that mechanisms underlying PCB 95-induced dendritic
growth are sex-dependent. These data highlight the importance of sex in
neuronal responses to environmental neurotoxicants.

早期生命阶段暴露于环境污染物，与多种神经发育障碍（Neurodevelopmental Disorders, NDDs）的发病机制密切相关。此类障碍往往表现出性别偏倚，但环境神经毒物是否以性别依赖的方式调控神经发育，目前尚不明确。鉴于树突形态改变与诸多NDDs相关，我们验证了如下假说：雌雄原代小鼠神经元对2,2′,3,5′,6-五氯联苯（PCB 95）的树突增殖活性具有不同的易感性。
我们于体外培养第7至9天，对海马及皮层神经元-胶质细胞共培养体系施加溶剂对照（0.1%二甲基亚砜，DMSO）或浓度范围为100飞摩尔至1微摩尔的PCB 95。经Sholl分析结果显示，PCB 95可促进雌性小鼠海马及皮层神经元的树突生长，但对雄性神经元无此作用。与之相反，雌雄神经元均能对荷包牡丹碱（bicuculline）产生响应，表现为树突复杂度提升。
细致的形态计量学分析证实，PCB 95对初级及非初级树突的数量与长度的影响，会因性别、脑区以及PCB浓度的不同而存在差异；且雌性神经元的树突生长增强响应更为稳定，且可在低于雄性体系的PCB 95浓度下被诱导。PCB 95暴露并未改变两种性别培养体系的细胞活力，亦未影响神经元与胶质细胞的比例。
上述结果表明，体外培养的雌性小鼠海马及皮层神经元，对PCB 95的树突增殖活性的敏感性高于雄性神经元；同时提示PCB 95诱导的树突生长机制存在性别依赖性。本研究数据凸显了性别在神经元响应环境神经毒物过程中的重要性。