Transcriptomics analyses reveal microgravity triggers estrogen synthesis amidst degeneration and aging in human ovarian granulosa cells.

Abstract

Advances in aerospace technology are making space travel accessible to more people. However, the space environment, especially unavoidable microgravity, poses health risks that are particularly concerning for women's reproductive endocrine health. While female estrogen secretion dysregulation represents a core concern, research on human ovarian granulosa cells, the primary site of estrogen synthesis, remains critically underdeveloped due to a scarcity of sequencing data, hindering both mechanistic investigation and intervention development. In this study, we performed transcriptomic analyses on human ovarian granulosa cells following microgravity exposure. Our analyses demonstrated that microgravity has multi-faceted effects on ovarian granulosa cells, disrupting cytoskeletal organization, mitochondrial function and Ca²⁺ transmembrane transport, as well as processes critical to follicular development and estrogen synthesis. Deconvolution analysis based on single-cell transcriptomics indicated microgravity-induced degeneration of granulosa cells, characterized by an increased proportion corresponding to primordial and primary follicular stages, although estrogen synthesis was upregulated. The data further demonstrated accelerated aging characterized by compromised DNA damage repair. Notably, anti-aging compounds including rapamycin were identified as potential countermeasures against microgravity-induced effects. Our research systematically characterizes microgravity-induced alterations in human ovarian granulosa cells, elucidates their implications for development and aging, and proposes feasible intervention strategies.