A mouse model engineered to spatiotemporally control Cre expression in progesterone receptor positive cells†

Area of Science:

• Reproductive Biology
• Genetics and Genomics
• Developmental Biology

Background:

• The Cre/loxP system enables site-specific genetic manipulation in mice.
• The PgrCre mouse model allows gene ablation in progesterone receptor (Pgr)-positive uterine cells but lacks temporal control.
• Existing models are limited for studying Pgr function in a time-specific manner.

Purpose of the Study:

• To develop and characterize an inducible PgriCreERT2 mouse model for spatiotemporally controlled gene ablation in Pgr-positive uterine cells.
• To investigate the role of Pgr in uterine function and fertility using tamoxifen-inducible gene manipulation.
• To establish a tool for precise investigation of uterine biology.

Main Methods:

• Generation and characterization of the inducible PgriCreERT2 mouse model.
• Crossing PgriCreERT2 mice with reporter mice (Rosa26-CAG-LSL-Sun1-sfGFP-myc) to confirm tamoxifen-dependent recombination.
• Crossing PgriCreERT2 mice with Pgrflox/flox mice to achieve tamoxifen-induced Pgr ablation.
• Assessing fertility and uterine function in tamoxifen-treated PgriCreERT2/Pgr:flox mice.

Main Results:

• Tamoxifen treatment induced recombination in uterine stromal fibroblasts and epithelial cells.
• Abating Pgr expression in PgriCreERT2/Pgr:flox mice led to implantation failure and dysregulated uterine cell proliferation.
• Treated mice showed loss of decidualization response, ovulation, and embryo transport were unaffected.
• A significant portion of treated mice became infertile, with reduced litter sizes.

Conclusions:

• The inducible PgriCreERT2 mouse model provides spatiotemporal control for gene ablation in Pgr-positive uterine cells.
• Pgr is crucial for uterine receptivity, implantation, and decidualization.
• This model is a valuable tool for studying uterine biology and reproductive processes.