Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China.
EBioMedicine. 2020 Oct;60:102993. doi: 10.1016/j.ebiom.2020.102993. Epub 2020 Sep 16.
This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS).
In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted.
Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty.
FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers.
This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).
本研究旨在探讨多囊卵巢综合征（PCOS）母亲所生女性后代神经行为发育改变的机制。
共招募了 20 名 PCOS 母亲和 32 名健康母亲（行剖宫产分娩且单胎为女性）。采用杜博维茨评分法评估婴儿。使用稳定过表达 FOS 的 Swan71 细胞系验证 FOS 对脑源性神经营养因子（BDNF）和神经生长因子（NGF）表达的调控作用。在青春期和成年期，采用 Morris 水迷宫测试 PCOS 大鼠模型中雌性第一代（F1）和第二代（F2）后代的学习和记忆能力。对雌性 F1 后代青春期海马和下丘脑的转录组进行分析。
PCOS 组女性婴儿的总评分和行为子评分均显著降低。PCOS 组胎盘绒毛中 FOS 和 NGF 蛋白水平下调。FOS 在 Swan71 细胞中对 BDNF 抑制和 NGF 增强起关键作用。与对照组相比，PCOS 雌性 F1 大鼠在青春期时的目标穿越时间更短。转录组分析显示，青春期雌性 F1 大鼠的海马和下丘脑神经元通路发生显著变化。
胎盘神经生长因子的 FOS 调节对 PCOS 母亲的女性后代的神经行为发育产生负面影响。
本研究由国家重点研发计划（2018YFC1004900 给傅启和傅伟）和国家自然科学基金（81874480 给傅启；81873837 给傅伟）资助。
