Evidence in support of a decidual clock for the timing of parturition

Evidence Key Points

The decidua is the maternal tissue most intimately
in contact with the feto-placental unit.
Immunological priming of the endometrium
appears to be critical to prevent rejection of the
The decidua is an
hemi-allogeneic conceptus, and this effect is
immunological organ
mediated through expansion of a specific subset of
(1) distinct from the
T-cells (Treg cells) within the endometrium.
placenta and other
Once pregnancy is established, selective
maternal tissues
epigenetic silencing of key T-cell-attracting
inflammatory chemokine genes in decidual
stromal cells appears to be critical for maintaining
pregnancy.
Endogenous levels of PGs in the decidua are 200-
fold lower in pregnancy than in the endometrium
at any stage of the menstrual cycle.
Failure to suppress PG production in the
endometrium around the time of implantation is
Suppression of
associated with spontaneous abortion.
decidual prostaglandin
(2) The administration of exogenous PGs, by any
(PG) synthesis is critical
route, at any stage of gestation, and in all species
for pregnancy success
examined, has the ability to induce abortion.
Levels of PGs increase in maternal plasma, urine,
and amniotic fluid before the onset of uterine
contractions, suggesting that this PG surge is the
cause and not simply a consequence of labor.
Familial clustering, racial disparities, the high
incidence of recurrent preterm birth, and studies
There is a genetic
in twins all suggest an important role for maternal
predisposition for
genetic factors in the timing of labor.
(3) preterm birth that is
A few target maternal genes of interest have been
carried primarily in the
identified.
maternal lineage
Epigenetic and gene-environmental factors are
likely also involved.
(4) Decidual dysregulation The final common pathway in the preterm birth
predisposes to preterm cascade likely involves a dysregulation (de-
birth: the two-hit repression) of decidual inflammation within the
hypothesis uterus.
A two-hit hypothesis has been proposed in which
a genetic predisposition (the first hit) primes the
decidua for an exaggerated inflammatory
response to a given environmental stimulus (the
second hit, often an ascending infectious insult).
Evidence suggests that the first hit may be an
underlying genetic predisposition (such as a
genetic variant in a gene coding for a key
proinflammatory mediator), but may also be an
early infection (bacterial or viral) or an underlying
medical condition (PCOS, endometriosis, obesity).