Fig. 5: Disruptions to reproductive tract development.
From: Spatiotemporal cellular map of the developing human reproductive tract
a, Heatmap showing the z score enrichment of targets of clinically approved drugs (x axis) that specifically affect the epithelial compartment of early (≤10 PCW) reproductive tract organs among reproductive-specific cell types (y axis) identified in our scRNA-seq dataset through drug2cell predictions. The colour of each drug represents its ATC code (details in Extended Data Fig. 9e). b, Schematic of the experimental design for uterine epithelial organoid derivation and exposure to the endocrine-disrupting chemicals BPA and BBP. Dimethyl sulfoxide (DMSO) was used as the control. c, Dot plot showing the predicted probability from each epithelial in vivo cell type (x axis) of the uterovaginal canal from which the organoids were derived and the non-ciliated and ciliated cells of the control organoids (y axis). d, Immunofluorescence staining of representative uterine epithelial organoids derived from a 17 PCW female fetus (Hrv277 line) at day 4 following exposure to BPA, BBP or vehicle (DMSO; Control) for EPCAM (magenta, epithelial cell marker), ZO-1 (cyan, tight junction protein indicating apicobasal polarity) and F-actin (white, cytoskeletal filament) (n = 2 biologically independent samples). Scale bars, 100 μm. e, Bar plot showing the proportion of ciliated and non-ciliated cells in fetal-derived uterine epithelial organoids treated with vehicle control (n = 21,905 cells) or BBP (n= 23,338 cells). f, Volcano plot showing the log fold change (x axis) and adjusted P value (y axis) of the differential expression of genes (adjusted P = 0.05, |log[FC] | > 0.5) between differentially abundant neighbourhoods in the BBP-exposed condition and all other neighbourhoods in non-ciliated G1 cells. Genes in bold are also upregulated by BPA. Illustrations in b created by A. García.
