RRBS, RNA-seq of placenta in women with PCOS and RNA-seq of hippocampus and hypothalamus in femal rats born to PCOS rats.

Polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism, irregular ovulation and polycystic ovaries. In the present study, we utilized integrated analysis of whole transcriptome and DNA methylome by reduced representation bisulfite sequencing (RRBS) and RNA sequencing (RNA-seq) of the fetal side of placenta in women with PCOS. A cluster of neural function related genes, such as LIN7A and MAP1B, were identified with integrative analysis of methylome and transcriptome. Inflammatory disease and response process were spotlighted with GO enrichments analysis of differentially transcriptional gene cluster in PCOS, and the cellular growth and the development and function of nervous and endocrine system were also closely related to PCOS. With respect to neural function, the enriched GO terms in differential expressed gene cluster of PCOS group involved brain development, the proliferation and differentiation of neural precursor cell, neuron and neuroblast. Consistently, the enriched GO terms in differential methylated gene cluster of PCOS group were associated with neuropeptide and synaptic transmission, as well as cognition and learning or memory. As the gene expression changes in hypothalamus and hippocampus probably result in long standing neurobehavioural consequences in rodents, we conducted a global analysis of transcriptomic data of F1 pubertal female rats born to PCOS rats. Overall design: RRBS and RNA-seq were performed on fetal side of placentae in women with PCOS and corresponding controls (n=3 in each group). RNA-seq was performed on hippocampus and hypothalamus in femal rats born to PCOS rats (n=3 in each group).