title: Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat.
abstract: Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways.
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK matthew.elmes@nottingham.ac.uk.
authors: Matthew
authors: M
authors: Elmes
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
authors: Alexandra
authors: A
authors: Szyszka
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
authors: Caroline
authors: C
authors: Pauliat
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
authors: Bethan
authors: B
authors: Clifford
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
authors: Zoe
authors: Z
authors: Daniel
authors: Royal Veterinary College, Reproduction and Development Group, Hatfield, UK.
authors: Zhangrui
authors: Z
authors: Cheng
authors: Royal Veterinary College, Reproduction and Development Group, Hatfield, UK.
authors: Claire
authors: C
authors: Wathes
authors: Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
authors: Sarah
authors: S
authors: McMullen
keywords: Maternal age; myometrium; parturition