Myometrial immune cells contribute to term parturition, preterm labour and post‐partum involution in mice

• Published in: Journal of cellular and molecular medicine Vol. 17; no. 1; pp. 90 - 102
• Main Authors: Shynlova, Oksana, Nedd‐Roderique, Tamara, Li, Yunqing, Dorogin, Anna, Lye, Stephen J.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2013; Blackwell Publishing Ltd
• Subjects: Activation; Animals; Cell Differentiation; Cell Movement; Chemokines; Cytokines; Differentiation (biology); Female; Flow cytometry; Gene Expression; Gestation; Humans; Immune system; Immunohistochemistry; infection; Infections; Inflammation; Inflammatory response; leucocyte infiltration; Leukocytes; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - immunology; Membranes; Mice; mifepristone; Mifepristone - pharmacology; Monocytes; Monocytes - cytology; Monocytes - drug effects; Monocytes - immunology; Musculoskeletal system; Myometrium; Myometrium - cytology; Myometrium - physiology; Neutrophils; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - immunology; Obstetric Labor, Premature - immunology; Obstetric Labor, Premature - pathology; Original; Parturition; Polymerase chain reaction; Postpartum Period - physiology; Pregnancy; Progesterone; Smooth muscle; Term Birth - physiology; Tissues; Uterus; United States > US
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2012.01650.x

This study aimed to determine the mechanism of uterine activation during labour, both term (TL) and preterm (PTL). We hypothesized that the peripheral leucocytes are recruited to uterine tissues by locally produced cytokines where they contribute to the initiation of parturition. Mouse uteri were collected (i) during gestation, TL and post‐partum (PP), (ii) during PTL initiated by intrauterine infusion of LPS (125 μg) or (iii) injection of the progesterone receptor antagonist RU486 and analysed for multiple cytokine expression levels by real‐time polymerase chain reaction (RT‐PCR) and 23‐plex Cytokine assay or enzymatically dispersed for assessment of immune cell populations. Markers of myeloid cell differentiation (Gr1, Neu7/4 and F4/80) were evaluated by FACS to define tissue macrophages (Macs), monocytes (M) and neutrophils (N) and by immunohistochemistry to detect tissue Macs and N. Our results indicate that: (1) Macs were elevated in mouse myometrium before TL (P < 0.05) followed by an increase in M and N; these changes were accompanied by an increase in multiple pro‐inflammatory cytokines/chemokines genes. The expression of corresponding proteins increased PP. (2) TL and RU486‐PTL models showed similar gene/protein expression profiles, (3) LPS‐PTL was characterized by strong pro‐inflammatory response and massive influx of N in myometrial tissues showing a pattern different from TL and RU486‐PTL, (4) The PP period appears similar in all three models, with elevated myometrial cytokine levels and high infiltration of immune cells. We concluded that leucocytes infiltrate myometrium around the time of parturition implicating their potential role in labour activation (both term and preterm) and major role in PP uterine involution.