Single-Cell Transcriptomic Analysis of the Potential Mechanisms of Follicular Development in Stra8-Deficient Mice

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genetics

Background:

• Follicle development is crucial for mammalian reproduction and fertility.
• Stra8 is a key regulator of meiosis initiation, but its complete role is unclear.
• Oocyte-like cells appear in Stra8-deficient mice, necessitating further investigation.

Purpose of the Study:

• To construct a transcriptional atlas of ovarian cells in wild-type and Stra8-deficient mice.
• To elucidate the molecular mechanisms underlying impaired folliculogenesis in Stra8 deficiency.
• To identify novel regulatory factors involved in early ovarian development.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of ovarian cells from embryonic stages E14.5 and E16.5.
• Transcriptional profiling of wild-type and Stra8-deficient mouse models.
• RNA interference (RNAi) analysis to validate gene function.

Main Results:

• scRNA-seq identified 14,755 cells across six major types, revealing heterogeneity between genotypes.
• Stra8 deficiency downregulated meiosis genes (e.g., Pigp, Tex12, Sycp3) and upregulated apoptosis genes (e.g., Fos, Jun, Actb).
• Elevated Sub1 and Stk31 expression in Stra8-deficient mice suggests their role in primordial follicle-like cell formation; Mdk-Sdc1 signaling disruption impacts PI3K/AKT pathway.

Conclusions:

• Stra8 plays a complex role in ovarian function, essential for proper meiosis and germ cell differentiation.
• Disruption of Stra8 impacts folliculogenesis by altering gene expression, promoting apoptosis, and affecting cell signaling.
• Sub1 and Stk31 emerge as potential regulators in primordial follicle development, warranting further study.