Abstract Pregnancy loss associated with excessive prostaglandin signaling and decidual injury remains a major clinical challenge, and few therapies directly stabilize the progesterone-dependent uterine environment. We tested whether allylestrenol (AL), an orally active progesterone receptor (PR) agonist, can protect against misoprostol (MSP)–induced pregnancy disruption in mice. In a GD7.5 MSP abortion model, AL co-treatment markedly reduced embryo resorptions and restored pregnancy success toward control levels. Histological examination of implantation-site decidua showed that MSP induced substantial epithelial and structural disruption, whereas AL largely preserved uterine architecture. Immunohistochemistry revealed that MSP downregulated PR and increased the inflammatory mediators COX-2 and IL-6, while shifting the BAX/BCL-2 balance toward a pro-apoptotic profile. AL reversed these molecular changes, restoring PR expression, attenuating COX-2 and IL-6 staining, and normalizing the BAX/BCL-2 ratio. Transcriptomic profiling supported these observations: RNA-seq demonstrated that MSP induced broad upregulation of inflammatory and apoptotic genes (including Il6, Il1b, Ccl4, and Bbc3) and downregulation of progesterone-responsive survival genes (Pgr, Stat6, Bcl2), whereas AL + MSP samples clustered closer to controls and showed partial restoration of these gene-expression patterns. Collectively, these data indicate that AL mitigates MSP-induced pregnancy loss by preserving PR signaling and limiting inflammatory and apoptotic responses in the decidua, supporting its potential as a progestin-based strategy for conditions in which pathological prostaglandin activity contributes to miscarriage.
Long et al. (Mon,) studied this question.
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