Mechanical stretch regulates hypertrophic phenotype of the myometrium during pregnancy

Abstract

The adaptive growth of the uterus is a critical event that involves changes in cellular phenotypes throughout pregnancy. In early pregnancy, uterine growth is due to hyperplasia of uterine smooth muscle cells (SMCs) within the myometrium; however, the major component of myometrial growth occurs after mid-gestation. This study sought to test the hypothesis that increase in myometrial growth seen during late pregnancy is due to SMC hypertrophy caused by mechanical stretch of uterine tissue by a growing fetus(es) by providing direct measurements of individual SMC size. We employed a stereological approach to calculate the average cell volumes of uterine myocytes through diameter measurements using the Stereoinvestigator statistical software. Uterine tissues were collected from nonpregnant Wistar rats, as well as from gravid and nongravid horns of unilaterally pregnant animals on gestational days (d) 8 (early gestation), 14 (mid-gestation), 19 (late gestation), 22 (term), and 4 days post partum. Anti-caveolin-1 immunostaining was used to clearly delineate SMC boundaries. The stereological analysis revealed that the dramatic increase in myometrial growth seen during late gestation (d19-22) is due to a threefold increase in the size of uterine myocytes. A significant increase in SMC volumes was detected in the gravid uterine horn as compared with the corresponding empty horn of unilateral term pregnant animals (day 22, mean cell volume 1114 vs 361 mm 3 , P!0.05), indicating the effect of uterine occupancy. The restriction of the hypertrophy to cells within the gravid horn suggests that it may be a response to the biological mechanical stretch of uterine walls by the growing fetus(es) and placenta(s).

Current versus future reproduction and longevity: a re-evaluation of predictions and mechanisms

“…Most studies designed to evaluate the mechanisms responsible for trade-offs between reproduction and longevity have either compared reproductive and non-reproductive animals or animals with varying levels of reproductive performance (Speakman and Garratt, 2014;Blount et al, 2015), and samples have largely been collected during the reproductive event for reproductive animals (Speakman and Garratt, 2014;Blount et al, 2015). Although negative consequences of reproduction may be initiated during this period, reproduction is typically a period of high physiological and morphological plasticity for females, with some organs experiencing hypertrophy or hyperplasia (Martin et al, 1973;Yu and Marquardt, 1974;Shynlova et al, 2010), while the function of other organs is down-regulated. As a result, it is impossible to untangle changes that support the metabolic demand of reproduction from changes that could have persistent effects on a female's probability of survival or on her fitness after the reproductive bout has ended.…”

The pathophysiology of human premature cervical remodeling resulting in spontaneous preterm birth: Where are we now?

“…(98,99) Towards the end of a normal pregnancy, Braxton-Hicks and labor contractions occur which further stretch the cervix. Given that i) tissue stress and stretch are an important mechanical factors in pregnancy, ii) smooth muscle cells can produce ECM and enzymes involved in remodeling ECM (94–97) and iii) uterine smooth muscle stretch can influence myometrial tissue remodeling (95–97,100), could cervical smooth muscle stretch influence cervical remodeling? Further, if cervical smooth muscle cells have altered ‘stretch’ sensors, could this trigger premature remodeling?…”

Pathogenesis and malignant transformation of adenomyosis (Review)

“…Increase in the growth of the uterus during pregnancy is due to smooth muscle cell hypertrophy and hyperplasia (16). Mechanical stretch is known to stimulate myometrial hyperplasia and hypertrophy through alteration of intracellular calcium signaling.…”