Nerve growth factor and its functional receptor TrkA are up-regulated in murine decidual tissue of stress-triggered and substance P-mediated abortion.
OBJECTIVE
Stress, elicited by environmental and social conditions, is known to affect the homeostasis of the nervous, endocrine and immune systems. In pregnancy, perceived stress results in a predomination of inflammatory abortion-associated Th1 cytokines over immunosuppressive, pregnancy-protective-associated Th2 cytokines, putatively via neuropeptide substance P (SP). Nerve growth factor (NGF), an important trophic factor for sympathetic neurons, has been implicated in the responsiveness of immune-competent cells through its functional receptor, tropomyosin receptor kinase (TrkA). Thus, the aim of the present study was to identify a cross-talk between distinct neurotrophic and immune mediators in pregnancy maintenance.


METHODS
Using immune fluorescence, we evaluated decidual and placental expression of NGF and TrkA on gestation day (gd) 13.5 in the abortion-prone mouse model CBA/J x DBA/2J in (1) CBA/J female control mice; (2) CBA/J mice exposed to stress on gd 5.5; and (3) CBA/J mice injected with SP on gd 5.5 to mimick stress perception.


RESULTS
Stress and SP injection significantly increased the abortion rate and up-regulated decidual NGF and TrkA expression compared with the control. Stress, but not SP injection down-regulated placental NGF, whereas no changes in placental TrkA were observed.


CONCLUSIONS
Our data suggest a functional role for NGF in stress-triggered, SP-mediated abortion.
Tometten
Mareike
M
Charité, Biomedizinisches Forschungszentrum, Campus Virchow, Humboldt University of Berlin, Berlin, Germany.
Klapp
Burghard F
BF
Joachim
Ricarda
R
Fest
Stefan
S
Zenclussen
Ana C
AC
Peters
Eva M
EM
Hertwig
Kai
K
Arck
Petra C
PC
D000034:Abortion, Veterinary / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D003656:Decidua / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism*; D011247:Pregnancy; D020917:Receptor, trkA / Q000378:metabolism*; D013312:Stress, Physiological / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology*; D015854:Up-Regulation
D013373:Substance P; D020932:Nerve Growth Factor; D020917:Receptor, trkA