The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

Abstract

Controversy still exists regarding the involvement of relaxin (RLX) in cervical reorganization throughout parturition in the human, despite its well-known role in facilitating extensive extracellular matrix (ECM) remodeling in diverse organs. Therefore, the aim of the present study was to examine the influence of RLX and estrogen (E2) on the cervical tissue of the common marmoset monkey. Two experimental designs were used: 1) in vivo analysis of the intracervical diameter under locally applied RLX and 2) ovariectomized (ov) marmosets were treated systemically with either recombinant human (rh) RLX, E2 or rhRLXCE2 to examine their action on the cervix. In vivo-locally applied rhRLX induced a distinct and significant widening of the cervix (before: 4.8G1.1 mm versus after: 5.7G0.9 mm in diameter; P!0.030, MVGS.E.M.). This widening effect was most pronounced in animals without previous pregnancies. In vitro investigation of cervical tissue showed significantly increased wet weights after all three hormone treatments (E2: 0.27G0.07 g, RLX: 0.25G0.04 g, E2C RLX: 0.30G0.11 g; all P!0.05; MVGS.E.M.) versus controls (0.10G0.04 g). Furthermore, morphological changes such as loosening of the connective tissue structure and decline in collagen content, an increase in the number of eosinophils, increased the expression of matrix metalloproteinases (MMP1) and MMP2, as well as gene and protein expression of the RLX receptor RXFP1 could be detected in the cervical tissue after all hormone treatments, compared with controls. In summary, RLX has a potent widening effect on the cervix of the common marmoset monkey. Although E2 is not required for this RLX effect, a combined application of E2 and RLX induced the most prominent cervical ripening.

Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

“…However, experiments with human cervical tissue are challenging because it is difficult to obtain sufficient cervical tissue during pregnancy [55]. Animal models, including the mouse, rat, primate, and guinea pig [29,[56][57][58][59][60] have been important for our current understanding of cervical remodeling. However, key differences exist between animal and human pregnancy.…”

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

“…Human cervical biopsy specimens have been obtained from patients in preterm and term labor, preterm and term nonlabor and nonpregnant patients after a hysterectomy to describe the cervical extracellular matrix and its relationship to abnormal labor [2][3][4][5][6][7][8][9][10][11][12][13]15,16,18,25,28,[46][47][48]. Animal studies have also provided insight into the changes in extracellular matrix that occur in the uterine cervix during pregnancy [17,[19][20][21][22]28,33,34,36,[49][50][51][52][53][54]. Studies of cervical biopsy tissue have been conducted in pregnant women as early as 1960 [18].…”

Cervical Tissue Engineering Using Silk Scaffolds and Human Cervical Cells

“…19,25 However, our prior work was limited because it was difficult to obtain cervical tissue from pregnancy of sufficient size to permit both biochemical and mechanical characterization. Many animal models (mouse, 28 rat, 29 primate, 30 rabbit, 31 and guinea pig 32 ) have been investigated to study the cervix during pregnancy, but cervical remodeling in animal models may not reflect changes in the human cervix. Therefore, a tissue engineering model using human cells may permit studies previously unavailable using conventional model systems.…”