Progesterone receptor isoform PGR-A in female fertility

The short PGR-A isoform lacks a 164 amino acid N-terminal region present in PGR-B that markedly enhances its transcriptional activity. Isoform-specific mutants inactivating either PGR-A (PRAKO) or PGR-B (PRBKO) indicated that PGR-A is specifically essential for female fertility.

This study revises that interpretation by showing that an inadvertent frame-shift mutation in the PRAKO caused ablation of both isoforms, instead of the intended PGR-A isoform-specific null mutation. A true PGR-A specific mutant generated through CRISPR-Cas9 editing with a complete lack of PGR-A, but retained expression of PGR-B showed a phenotype indistinguishable from wild type as previously shown for PRBKO females. Thus, the distinct function of PGR isoforms is more nuanced than previously appreciated.