The swelling behavior of the mouse cervix: Changing kinetics with osmolarity and the role of hyaluronan in pregnancy

The cervical remodeling process during pregnancy is characterized by progressive compositional and structural changes in the tissues extra-cellular matrix (ECM). Appropriately timed remodeling is critical for healthy gestation and prevention of premature cervical softening leading to preterm birth (PTB). Modification of the ECM glycosaminoglycans (GAGs) content with advancing pregnancy, especially the non-sulfated GAG hyaluronan (HA), is a fundamental change associated with cervical remodeling. While GAGs have numerous physiological roles, the mechanical consequence of evolving GAG content on cervical structure-function behavior remains an open question. Additionally, an understanding of cervical swelling properties, postulated to be regulated in part by GAGs, is required for the appropriate definition of a reference configuration for mechanical tests and to enhance biological understanding. To investigate cervical swelling, osmotic loading tests are conducted on isolated wild type mouse cervices throughout pregnancy. These tests are performed in various osmolarity solutions to assess the influence of the media on swelling kinetics. A genetically altered strain of mice with depletion of cervical HA is also tested to elucidate the contribution of HA to tissue swelling. Results show ex vivo cervical swelling is significant with volume changes ranging from 20 to 100% after 3h of free swelling. The swelling kinetics depend highly on osmolarity of the media and is altered with advancing pregnancy. The contribution of HA to swelling is only significant in hypo-osmotic solution when HA cervical content is high at the end of pregnancy. In summary, it is critical to account for swelling deformation mechanisms after excision in mechanical experiments. STATEMENT OF SIGNIFICANCE: The cervical extracellular matrix (ECM) undergoes drastic changes to fulfill the functional change of the cervix during pregnancy. Inappropriate timing for this transformation can result in preterm birth, a severe clinical challenge. One of the fundamental changes of the cervical ECM is the significant modification of the glycosaminoglycan content, especially hyaluronan (HA), which is thought to contribute significantly to the swelling and mechanical properties of the cervix. This study aims to measure the swelling kinetics of cervical tissue during pregnancy and to investigate the role of HA in these swelling tendencies. Results show the significant swelling of cervical tissue, which evolves as pregnancy progresses, highlighting a key material property feature of the remodeled cervix. Using a mouse strain with a cervical HA depletion, this work shows HA contributes to the swelling trends of late-term cervical tissue, in a hypo-osmotic solution.