Spatial atlas of human embryos shows kidney, adrenal and gonad development are linked

Researchers in China have built a spatially resolved atlas of the developing human urinary and reproductive tracts, and it indicates that adjacent organs influence one another's fate. The work, published in Science, was led by Guo Jingtao and Wang Xiaoyan at the Institute of Zoology, Chinese Academy of Sciences. Peking University Third Hospital and the Women and Children's Hospital at Qingdao University also took part.

Why tissue position matters

The kidney precursor (mesonephros), the adrenal primordium and the gonadal primordium all arise from the same embryonic tissue, the intermediate mesoderm, around weeks four to five of gestation. They also sit side by side. Earlier single-cell work defined the cell types inside each organ, but breaking tissue into separate cells erases information about who is next to whom. That makes it hard to test whether one organ signals to another.

The team analysed male and female embryos at Carnegie stages 15, 19 and 23, which cover gonad specification and the onset of sex differentiation. They paired Stereo-seq spatial transcriptomics with single-cell multi-omic profiling, protein imaging and human embryonic stem cell cultures. The spatial data were sorted into 33 cell types. Lineage reconstruction placed kidney-related cells on a path that separates early, while adrenal cortical cells and gonadal somatic cells stayed more alike.

Neighbours as a source of gonadal cues

At stage 15, computational analysis of cell-to-cell communication suggested that the gonadal primordium receives WNT, BMP and NCAM signals from the mesonephros and adrenal primordium. The researchers tested this in the laboratory by exposing stem-cell-derived intermediate mesoderm to BMP7, NCAM1 and the WNT activator CHIR99021. Together, the three factors raised early gonadal marker expression and moved the gene expression profile closer to that of early gonadal tissue in embryos. The authors conclude that nearby tissues can help set early gonadal identity.

A possible extra origin for supporting cells

Where the rete testis or rete ovarii forms, the team found cells expressing PAX8. These resembled mesonephric mesenchyme more than early gonadal somatic cells, pointing to a mesonephric origin. Combining pseudotime analysis, single-nucleus RNA sequencing, chromatin accessibility data, spatial mapping and immunofluorescence, the researchers identified cells showing traits of both rete cells and gonadal supporting cells.

Read alongside earlier mouse Pax8 lineage-tracing results, this hints at a non-canonical route by which mesonephros-associated rete cells could supply some supporting cells. Computational perturbation and PAX8 knockdown in cultured cells suggested that the protein helps preserve rete identity and may hold back conversion to a supporting-cell state. The authors present this as a suggestion rather than a proven lineage relationship.

Hormone-producing cells in adrenal and gonad

In the first trimester the analysis found three distinct steroid-producing populations: fetal Leydig cells in the male gonad and two states of the adrenal fetal zone, termed FZ_state I and FZ_state II.

• FZ_state I showed a strong programme for making cholesterol from scratch, marked by SREBF2.
• FZ_state II expressed the lipoprotein receptors SCARB1 and LDLR along with genes for cortisol synthesis, suggesting it draws cholesterol from circulating lipoproteins and can produce cortisol.

The authors link this to sex differentiation. Cortisol is thought to restrain androgen levels through negative feedback, which would shield female development. Male gonadal steroid-producing cells appear after stage 19 and express androgen-synthesis genes, whereas their female counterparts do not arise until puberty.

Implications and next steps

The findings portray urogenital development as an integrated process in which chemical signals, cell communication and hormones are shared across organs. For researchers, that offers a framework for asking how disturbed coordination might underlie congenital anomalies and differences of sex development. The study team has released an interactive platform so others can explore the spatial and multi-omic datasets.

Several caveats apply. The source summary does not give the number of embryos analysed, and much of the evidence for signalling and for PAX8 function rests on computational inference and cell-culture models, not on experiments in intact human embryos, which are not feasible. The rete-to-supporting-cell contribution in particular awaits direct lineage evidence in humans. The reference is Guo et al., Science (2026), DOI: 10.1126/science.aee5093.

Source: Spatial mapping reveals how human urogenital organs codevelop during organogenesis (Phys.org, 31 October 2026).

Image: AI-generated illustration.