ESPE Yearbook of Paediatric Endocrinology

Sci Adv. 2022; 8(16): eabn8485. PMID: 35442744https://pubmed.ncbi.nlm.nih.gov/35442744/

Brief Summary: This histologic and transcriptomic study of human and primate adrenal tissue samples provides a molecular framework to understand the fetal development of the adrenal gland.

The adrenal cortex is the major source of steroid hormones that drive a plethora of critical physiologic functions. Accordingly, developmental abnormalities in the formation of the adrenal cortex lead to various congenital and adult-onset diseases. Mammalian gonads (ovaries and testes) also produce steroid hormones, and commonalities exist between the adrenal cortex and gonads in both their steroid synthetic pathways and developmental origin. In humans, the gonads and the adrenal cortex are first recognized as morphologically distinct structures at approximately 33 days after conception [Carnegie stage (CS) 15], at which time the adrenal cortex is recognized as a condensed blastematous structure, medial to the mesonephros, referred to as the adrenal primordium (1-3). However, because of the lack of genetic tracing tools or appropriate markers to differentiate emerging gonadal and adrenocortical lineages, how and when these lineages are specified and segregated remain poorly understood in humans.

These authors provide evidence that, in contrast to mice, the adrenal cortex in humans and cynomolgus monkeys originates in a spatially, temporally, and phenotypically distinct manner from that of the gonads. Specifically, through histologic and transcriptomic analyses of early human gonadogenesis, they found that the gonad is established from the posterior coelomic epithelium (CE) at 4 to 5 weeks post-fertilization through the sequential activation of GATA4 and NR5A1, similar to mice and cynomolgus monkeys. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. They demonstrated that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. In summary, these findings reveal the distinct origin of the human and infrahuman primate adrenal cortex and gonads, and provide an example of the divergence of organ morphogenesis between species, essential insight for understanding human adrenogenesis and gonadogenesis, and a molecular framework for understanding human adrenal and gonadal disorders.

References: 1. Pignatti E, Flück CE. Adrenal cortex development and related disorders leading to adrenal insufficiency. Mol. Cell. Endocrinol. 2021; 527: 111–206. 2. Ishimoto H, Jaffe RB. Development and function of the human fetal adrenal cortex: A key component in the fetoplacental unit. Endocr. Rev. 2011; 32: 317–355. 3. Fabbri-Scallet H, de Sousa LM, Maciel-Guerra AT, Guerra-Júnior G, de Mello MP, Mutation update for the NR5A1 gene involved in DSD and infertility. Hum. Mutat. 2020; 41: 58–68.