Title page for ETD etd-09102008-161838


Type of Document Dissertation
Author Lyle, Sara K.
Author's Email Address slyle@lsu.edu
URN etd-09102008-161838
Title The Relationship between Pro-inflammatory Cytokines, Prostaglandins, and Fetal Hypothalamic-Pituitary-Adrenal Axis Activation in Mares with Infective Pre-term Delivery
Degree Doctor of Philosophy (Ph.D.)
Department Veterinary Clinical Sciences
Advisory Committee
Advisor Name Title
Dale L. Paccamonti Committee Chair
Bruce E. Eilts Committee Member
David W. Horohov Committee Member
Jill R. Johnson Committee Member
Robert A. Godke Committee Member
John E. Chandler Dean's Representative
Keywords
  • placenta
  • fetal fluids
  • horse
  • placenta
  • cytokines
  • prostaglandins
  • cortisol
  • fetus
  • Streptococcus
Date of Defense 2008-08-08
Availability unrestricted
Abstract
Ascending placentitis is a significant cause of abortions, stillbirths, and perinatal loss in horses. A technique for laparoscopic-guided catheterization of the allantoic space was developed and utilized in an experimental model of streptococcal infective pre-term delivery in pony mares. Mares received either 1 x 107 CFU live S. zooepidemicus (n=3), 5.1 x 108 CFU live S. zooepidemicus (n=1), 1 x 107 heat-killed S. zooepidemicus (n=3), 1 mL sterile PBS (n=3). Sham control mares did not receive a transcervical inoculation (n=3). One mare not instrumented with an allantoic catheter received 5.1 x 108 CFU live S. zooepidemicus. Mares with spontaneous abortion had significantly increased CTUP compared to mares in which delivery was induced. There was not a significant effect of infection within the allantoic space on CTUP. Intrauterine infection increased the expression of IL-1, IL-18, IL-15, and IFN- in a site-dependant manner. Spontaneous abortion also increased the expression of IL-1, IL-18, IFN-, and iNOS in a site dependant manner. Soluble TNF- was detected in only a few samples of fetal fluids. The concentrations of PGE2 and PGF2 in fetal fluids were increased within 24 h of delivery in mares with spontaneous abortion or intrauterine infection. Increased cortisol concentrations were observed in fetal fluid in some mares with infection or with histologic inflammation of the chorioallantois. None of the fetal fluids from mares induced to deliver or without inflammation of the chorioallantois had increased cortisol concentrations. This data suggests that the equine fetal adrenal gland less than 295 d may be capable of response to stimuli. Based on these findings, the following sequence of events leading from intrauterine infection to infective pre-term delivery is proposed. Following infection of the chorioallantois, IL-1, IL-18, IL-15, and IFN- are upregulated in a site-dependant manner. IL-1 causes increased PGHS-2 (COX-2) expression, resulting in increased PGE2 and PGF2 production, and ultimately labor. IL-1 may also accelerate fetal hypothalamic-pituitary-adrenal axis (HPAA) activation, thereby promoting precocious in utero fetal maturation. The eventual outcome of pre-term labor, i.e., neonatal survivability, will depend on the degree of HPAA activation at the onset of labor.
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