Striking Changes in the Structure and Organization of Rat Fetal Membranes Precede Parturition1

Abstract

Premature rupture of fetal membranes can harm infant and mother. It is unclear whether structural changes predispose these membranes to breaking. We thus assessed rat visceral yolk sac placenta (VYSP) and amnion by light and by transmission electron microscopy on Days 18-21 of gestation. Light microscope sections were stained for connective tissue (extracellular matrix) components: collagen, glycoprotein, and glycosaminoglycans/proteoglycans. Some tissue was incubated with chondroitinase ABC. We observed that fetal membranes became increasingly fragile, rupturing readily on Day 21. On Days 18-20, the two epithelial layers of the capsular VYSP were separated by a well-developed, well-vascularized connective tissue layer that stained intensely for all matrix components studied; on Day 21, the connective tissue layer was thinner, moderately stained, and less vascularized. On Days 18-20, the two cellular layers of the amnion were separated by a narrow, compact connective tissue layer that stained modestly for all matrix components; on Day 21, this area was widened and stained faintly. Transmission electron microscopy showed that collagen fibrils of the amnion were abundant, closely packed, and well organized on Days 18-20, whereas on Day 21 they were few in number, widely spaced, and disorganized. Similar changes were present after incubation with chondroitinase ABC. In addition, amniotic epithelial cells were moribund and delaminating, basal laminae were deteriorating or absent, and few cells were at the outer surface of the amnion. All changes preceded parturition. We conclude that the structural integrity of rat fetal membranes is impaired before birth through the loss of connective tissue components and cells, changes that presumably underlie membrane rupture. Lastly, the similarity of structural changes in rat and human fetal membranes point to the potential usefulness of the rat model.

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…Although animal data document homogeneous weakening of the FM over the entire surface with increasing gestation (Lei et al, , 1997Paavola et al, 1995;Parry et al, 1998), attempts to demonstrate similar gestational changes in human FM were unsuccessful (Manabe et al, 1991). Studies in which whole FM or randomly selected pieces were sampled showed high variability and no definite pattern of remodeling and apoptosis.…”

Term Human Fetal Membranes Have a Weak Zone Overlying the Lower Uterine Pole and Cervix Before Onset of Labor1

“…Recent 1 data in the rat model suggest that the amnion, the component of the fetal membrane (FM) with the major tissue strength, undergoes collagen remodeling as gestation progresses [2,3]. Apoptosis has also been observed in rat amnion following end-gestational remodeling [3,4]. As a result of remodeling and apoptosis, the FM is postulated to weaken and be more susceptible to tearing near the end of gestation [3, 4,].…”

A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

“…During labor, the membranes usually rupture, a process that has been attributed frequently to mechanical forces (1). Recently, we characterized the histological and ultrastructural features of the rat fetal membranes, the amnion and visceral yolk sac placenta, at the end of pregnancy and discovered striking changes in the cells comprising the membranes as well as the extracellular matrix before the onset of active labor (2). These structural changes were particularly marked in the amnion and included delamination of amnion epithelial cells from the amnion basement membrane, ultrastructural signs of apoptosis, and a dramatic loss of fibrillar collagen from the amnion matrix.…”

“…The goals of this study were to determine if cells of the amnion display characteristic biochemical features of apoptosis at term, including nuclear DNA fragmentation (3) and degradation of ribosomal RNA (4), and if these changes are associated with the activation of collagenolytic enzymes that degrade the primary amnion fibrillar collagen, type I collagen (2,5).…”