Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: II. Effects of DES on development

Abstract

The effects of diethylstilbestrol (DES) treatment on myometrial development from the prenatal to adult period were examined in rats and mice by histologic and immunocytochemical methods using anti-actin, -vimentin, and -laminin to assess cytodifferentiation of smooth muscle and fibroblastic cells, and by morphometric procedures to assess quantitatively the effect of DES on the expression of cellular orientation in the emerging inner circular myometrial layer. Neonatal rats and mice were treated with DES from day 0 (day of birth) to day 2 with dosages known to perturb myometrial development. Neonatal treatment with DES increased the degree of circular orientation within the uterine mesenchyme, an effect detectable following as little as 24 hr of DES treatment. This effect on spatial organization of the mesenchyme was followed by an increase in the thickness of the actin-positive middle layer (prospective circular myometrium) of uterine mesenchyme during days 3-15; from day 15 onward, however, the circular myometrial layer began to fragment into irregular bundles of smooth muscle, and the longitudinal myometrial layer became thinner and more irregularly organized than controls. Vimentin localization in rats treated with DES neonatally was more intense than in controls within the circularly orientated uterine mesenchyme at 5 days. By 60 days the circular and longitudinal myometrial layers of DES-treated animals showed strands and bundles of vimentin-positive cells, which were not present in controls. Both rats and mice show comparable effects of DES treatment.

Effects of Neonatal Diethylstilbestrol (DES) Exposure on Morphology and Growth Patterns of Endometrial Epithelial Cells in CD-1 Mice

“…Squamous metaplasia, representing an altered cellular phenotype in response to hormones at puberty (18), was not observed, probably because of the young age of the DES-exposed animals in this study. The mesenchymal tissues of the uterus exposed neonatally to DES also displayed obvious effects of DES exposure, such as disorganization of stromal and myometrial layers by the eighth day of age and subsequent stromal fibrosis, which has also been previously reported (6 (5). Programmed cell death is considered to be a genetically encoded process of active selfdestruction of cells (7), and it plays an important role in maintaining homeostasis by eliminating excessive and/or abnormal cells in tissues; it is also essential for the control of cell proliferation and/or differentiation at the developmental stage (5).…”

Fetal and early postnatal environmental exposures and reproductive health effects in the female

“…In contrast to humans, in which reproductive tract development occurs primarily in utero, the majority of rodent uterine differentiation and maturation occurs postnatally (61). At birth, the rat uterus is comprised of the luminal epithelial layer of the endometrium and a randomly ordered, undifferentiated uterine mesenchyme.…”

Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium

“…In rodents (as in most mammals, but not humans [33]), the myometrium can be divided into two distinct layers of smooth muscle: the inner circular layer and the outer longitudinal layer [34]. Our experimental data indicate downregulation of Cx45 expression in the rat as labour approaches, in contrast to Cx43 expression where no change at the end of pregnancy appears to be evident.…”