Successful pregnancy outcome requires balanced networking of the immune and
endocrine system. In addition, numerous sophisticated adaptive mechanisms promote invasion
of fetal tissue and facilitate tolerance. This highly sensitive and vulnerable environment
may be challenged from either the maternal or the fetal site. In this overview we collect evidence
of a functional role of neurotrophins, predominately nerve growth factor (NGF), in
pregnancy maintenance. We demonstrate several pathways through which NGF may be
involved in maintaining pregnancy and/or - if exaggerated - inducing pregnancy failure. Due
to the pleiotropism of NGF, we hypothesize that NGF is mandatory for the success of pregnancy,
e.g. via inhibition of paternal MHC II molecule expression on trophoblast cells. This
is supported by published evidence on progesterone, the hormone of pregnancy, which maintains
local levels of NGF. On the other hand, if levels of NGF are upregulated in response to
environmental challenges, e.g. stress, this may result in a threat to pregnancy maintenance
due to a skew towards proinflammatory cytokines and increased apoptotic cell death. Hence,
we strongly suggest that NGF constitutes a functional link between the nervous, endocrine
and immune system translating environmental or endocrine signals during pregnancy into an
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