Vaginal Progesterone Administration Subtly Influences Biomechanics and Composition of Mouse Cervix in Pregnancy

Abstract During pregnancy, the cervix provides mechanical support for the developing fetus and then dynamically remodels during late gestation to soften and enable parturition. Dysfunction of the cervix can therefore lead to preterm birth, a leading cause of neonatal morbidity and mortality. Progestational agents have been extensively studied for preterm birth prevention, yet data on their direct biomechanical impact on the cervix are limited. Therefore, this study aimed to investigate the biomechanical and compositional effects of systemic and vaginal progesterone administration on cervical tissue integrity in mice during late gestation. Pregnant mice received daily systemic or vaginal progesterone from gestational days 14–17 and were compared to vehicle controls. Cervical tissues were harvested six hours after the final treatment for structural, mechanical, and compositional assessment. Systemic progesterone treatment did not produce changes in cervical structure, mechanical properties, or extracellular matrix composition. In contrast, vaginal progesterone increased cervical tangent modulus at different stages of fatigue life. Vaginal progesterone also reduced cervical cross-sectional area and water content, while increasing collagen concentration relative to wet weight, suggesting that its biomechanical effects may be mediated through modulation of tissue hydration. These findings provide a plausible biomechanical basis for the clinical efficacy of vaginal progesterone in preventing preterm birth by preserving cervical mechanical stability and attenuating premature softening.