TY - JOUR
T1 - Exosomes Cause Preterm Birth in Mice
T2 - Evidence for Paracrine Signaling in Pregnancy
AU - Sheller-Miller, Samantha
AU - Trivedi, Jayshil
AU - Yellon, Steven M.
AU - Menon, Ramkumar
N1 - Funding Information:
Authors acknowledge support by all the staff from the Maternal-Fetal Medicine and Perinatal Research Laboratory, University of Texas Medical Branch at Galveston (UTMB), TX, USA. We specifically acknowledge the contributions of Egle Bytautiene-Prewit, MD, PhD, and Phyllis Gamble for providing their expertise in animal studies, Talar Kechichian, MS, (laboratory manager) for her expertise in protein chemistry and western blot analysis of samples, and Katherine Haver and Rheanna Urrabaz-Garza for their assistance in macrophage quantification. Cryo EM was performed at the electron microscopy core laboratory at UTMB with support and guidance from Michael Woodson, PhD. Statistical analysis was performed with the guidance from Heidi Spratt, PhD. Samantha Sheller-Miller is an appointed Pre-Doctoral Trainee in the Environmental Toxicology Training Program (T32ES007254), supported by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) of the United States, and administered through the University of Texas Medical Branch in Galveston, Texas. This study was supported by a grant from AMAG Pharmaceuticals to R. Menon. The macrophage localization and activation studies were performed in Dr. Steve Yellon’s laboratory that was supported by grant funding (NIH HD954931).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Endocrine factors and signals of fetal organ maturation are reported determinants of birth timing. To test the hypothesis that paracrine signaling by exosomes are key regulators of parturition, maternal plasma exosomes from CD-1 mice were isolated and characterized throughout gestation and the biological pathways associated with differentially-expressed cargo proteins were determined. Results indicate that the shape and size of exosomes remained constant throughout gestation; however, a progressive increase in the quantity of exosomes carrying inflammatory mediators was observed from gestation day (E)5 to E19. In addition, the effects of late-gestation (E18) plasma exosomes derived from feto-maternal uterine tissues on parturition was determined. Intraperitoneal injection of E18 exosomes into E15 mice localized in maternal reproductive tract tissues and in intrauterine fetal compartments. Compared to controls that delivered at term, preterm birth occurred in exosome-treated mice on E18 and was preceded by increased inflammatory mediators on E17 in the cervix, uterus, and fetal membranes but not in the placenta. This effect was not observed in mice injected with early-gestation (E9) exosomes. This study provides evidence that exosomes function as paracrine mediators of labor and delivery.
AB - Endocrine factors and signals of fetal organ maturation are reported determinants of birth timing. To test the hypothesis that paracrine signaling by exosomes are key regulators of parturition, maternal plasma exosomes from CD-1 mice were isolated and characterized throughout gestation and the biological pathways associated with differentially-expressed cargo proteins were determined. Results indicate that the shape and size of exosomes remained constant throughout gestation; however, a progressive increase in the quantity of exosomes carrying inflammatory mediators was observed from gestation day (E)5 to E19. In addition, the effects of late-gestation (E18) plasma exosomes derived from feto-maternal uterine tissues on parturition was determined. Intraperitoneal injection of E18 exosomes into E15 mice localized in maternal reproductive tract tissues and in intrauterine fetal compartments. Compared to controls that delivered at term, preterm birth occurred in exosome-treated mice on E18 and was preceded by increased inflammatory mediators on E17 in the cervix, uterus, and fetal membranes but not in the placenta. This effect was not observed in mice injected with early-gestation (E9) exosomes. This study provides evidence that exosomes function as paracrine mediators of labor and delivery.
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U2 - 10.1038/s41598-018-37002-x
DO - 10.1038/s41598-018-37002-x
M3 - Article
C2 - 30679631
AN - SCOPUS:85060513485
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 608
ER -