Endocrine Abstracts

JOINT1675

Introduction: Minipuberty, a transient activation of the Hypothalamic-Pituitary-Gonadal (HPG) axis in early infancy, plays a crucial role in early gonadal maturation and serves as a diagnostic window for future reproductive function. Despite its critical importance, particularly in males, the molecular mechanisms and dynamics underlying minipuberty remain poorly understood. Rodent models offer limited insights, as they lack an activity phase comparable to human minipuberty. To address this gap, we aimed to investigate cell-specific expression and chromatin accessibility dynamics in the hypothalamus, specifically the arcuate nucleus/median eminence (ARC/ME) region, using male marmosets (Callithrix jacchus) as a translational model during this critical developmental phase.

Objectives and methods: We profiled a total of 9 animals from 3 developmental stages: newborn (0–1 day), 3-week-old (during minipuberty), and 12-week-old (post-minipuberty). In addition to brain tissues, serum was collected and androgen levels were measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) to further validate the selection of these developmental stages.

Results: Single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus generated a comprehensive dataset of over 70,000 nuclei, allowing for the identification of distinct neuronal and non-neuronal populations. Analysis revealed stage-specific transcriptomic shifts across major cell types during early postnatal development, highlighting dynamic changes in hypothalamic function. We successfully profiled key HPG axis-regulating neurons, including KISS1-expressing populations, which play a central role in GnRH signaling. Additionally, hormonal measurements confirmed significant differences in androgen levels between developmental stages, supporting the physiological relevance of the selected time points.

Conclusions: These findings provide high-resolution insights into hypothalamic neuroendocrine regulation, emphasizing its role in growth and reproductive hormone dynamics during postnatal maturation. The observed stage-specific transcriptomic shifts and hormonal differences contribute to a deeper understanding of HPG axis activation and suppression, offering a framework for studying minipuberty and its implications for reproductive development.