A Transcriptomic Atlas of Primate Ovarian Aging in Single Cells
Summary
In the examination of the enigmatic process of ovarian aging and its influence on female fertility, researchers analyzed the unique cellular compositions and behaviors in ovaries from young and mature non-human primates. Their analysis divulged seven diverse cell classifications, including a variety of ovarian somatic cells and oocytes, each exhibiting unique genetic expressions. A detailed study of these expressions highlighted progressive alterations associated with aging, specifically pinpointing oxidative damage in initial-stage oocytes and granulosa cells due to impaired antioxidant signaling. The enhanced presence of reactive oxygen species and apoptotic activities was also noted in the granulosa cells of aged females. Such findings offer enriched insights and pave avenues for diagnosing and treating age-linked ovarian complications.
Fig.1 Graphical abstract1.
Research Criteria
The study aimed to understand the molecular mechanisms of ovarian aging and female age-related fertility decline. The researchers surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures. They further dissected the gene-expression dynamics of oocytes and analyzed cell-type-specific aging-associated transcriptional changes.
Fig.2 Experimental design1.
Sample Type
The samples used were ovaries from young (4-5 years old) and aged (18-20 years old) cynomolgus monkeys. The aged monkeys were in the period of pre-menopause or peri-menopause, making them suitable for studying ovarian aging.
Result—The Single Cell Transcriptome Profiling of Monkey Ovaries Revealed Various Ovarian Cell Types and Gene Expression Signatures
In an intricate exploration of the cynomolgus monkey's ovarian cellular landscape, researchers employed single-cell RNA sequencing to discern the nuanced gene expression patterns inherent to ovarian aging. By meticulously segmenting the ovary into cortex and medulla, and subsequently subjecting it to rigorous enzymatic digestion, they garnered high-fidelity transcriptomes from a collection of 2,601 cells, encompassing both oocytes and somatic cells. Leveraging the SCENIC analysis, they astutely identified seven predominant cell types, elucidating that the distribution of these cellular types remained consistent across varying age groups, thereby negating any age-induced biases. This comprehensive profiling illuminated pivotal transcriptional regulators, such as FIGLA for oocytes and NR5A2 for granulosa cells. Furthermore, the study unveiled novel markers for oocytes, including LMOD3, RBM46, and NETO1, enriching the understanding of oocyte differentiation. Granulosa cells, stromal cells, and other somatic cells were also meticulously characterized, each revealing distinct gene expression signatures. This seminal work, thus, offers an enriched tableau of the monkey ovarian cellular milieu, delineating both established and novel markers, and underscoring the intricate dance of gene expression that underpins ovarian function.
Fig.3 Single Cell RNA-seq analysis of monkey ovaries identifies distinct ovarian cell subpopulations with transcriptional signatures1.
Result—Signatures of Gene Expression in Four Oocyte Subtypes at Sequential and Stepwise Developmental Stages
Delving into the complexities of oocyte gene-expression during folliculogenesis, researchers identified four unique oocyte subtypes, labeled C1 to C4. Through principal component analysis, it became evident that these subtypes represent a methodical developmental progression. Essential genes for follicular development, such as ZP1, BMP15, and GDF9, showed an incremental upregulation from C1 to C4. In contrast, genes like ATP6 and COX2, typically linked with primordial follicles, manifested a decreasing expression trend. Such patterns suggest that the oocyte subtypes, from C1 to C4, correspond respectively to primordial, primary, secondary, and antral follicles. A Gene Ontology (GO) analysis further demystified the predominant biological processes at each stage, with findings like the "electron transport chain" being enriched in subtype C1 and "meiosis I" in subtype C4. The research also highlighted the evolving expression of meiosis-related genes, emphasizing their increasing prominence as follicles transition from primordial to antral stages. This meticulous study provides profound insights into the nuanced gene-expression programs and stage-specific transcriptional networks integral to folliculogenesis.
Fig.4 Oocyte subtypes' dynamic gene expression patterns at different developmental stages1.
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Reference
- Wang, Si, et al. "Single-cell transcriptomic atlas of primate ovarian aging." Cell 180.3 (2020): 585-600.
