Maturation of ovine uterine smooth muscle during development and the effects of parity

OBJECTIVES: TO characterize changes in myometrial contractile proteins and myosin heavy chain (MHC) isoforms during ovine fetal and neonatal development and after pregnancy. We hypothesized that ovine myometrium demonstrates progressive cellular differentiation and maturation which begins in utero and extends into the postnatal period, and that pregnancy causes further cellular alterations. METHODS: Myometrium was obtained from female fetal (72- to 140-days of gestation, n = 19; term similar to 145 days), postnatal (1 day to 3 months, n = 25), and parous noncycling nonpregnant (n = 3) sheep to measure total and soluble proteins, actin, MHC, and MHC isoforms. Contractile proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and expression of 200-kD A IHC isoforms were determined with Western immunoblots. RESULTS: The contents of total and soluble proteins and actin and total myosin gradually increase (P < .003) during ovine development. Although the contribution of smooth-muscle 204-kD MHC increased (P < .001) from 23 +/- 8% of total MHC at < 100 days of gestation to 75 +/- 2% 3 to 4 months postnatally, the 200-kD species fell proportionately. Before birth, MHC-B, a fetal isoform, is the predominant 200-kB protein postnatally, it is replaced by SM2, demonstrating a switch from synthetic to a mature contractile smoot-muscle phenotype. Pregnancy is associated with further increases in actin contents and redistribution of the contents of the 204-kD and SM2 HC isoforms. CONCLUSIONS: Although the fetal and postnatal uterus has no known functional demand, ovine myometrial differentiation and maturation begin in the midtrimester and continue throughout the postnatal period. Thus, changes ill smooth-muscle phenotype occur prenatally, as evidenced by a switch from MHC-B to SM2, which may signal completion of organ development and preparation for adult function. Pregnancy results in further modifications in myometrial proteins. Copyright (C) 2000 by the Society for Gynecologic Investigation.