This is a mechanism module, not a disease. Do NOT create a "Defective Deep Placentation" Disease entry: the lesion is a placental-bed finding that is diagnosed on targeted biopsy and has no standalone clinical identity or MONDO term. Disorder entries reference individual nodes via conforms_to, e.g. "deep_placentation_defect#Failure of Spiral Artery Physiological Transformation".
Species caveat. Deep interstitial and endovascular trophoblast invasion as far as the junctional-zone myometrium is essentially restricted to humans and the great apes; the mouse and rat models that supply most mechanistic data invade far more shallowly, so a rodent result should be linked with FAILS_TO_RECAPITULATE or a recorded fidelity caveat rather than read straight across. No animal or computational models are attached to this module for that reason - they belong on the conforming disorder entries, where the specific caveat can be stated.
Wired conformers at the time of creation: Preeclampsia ("Defective Trophoblast Invasion and Spiral Artery Remodeling"), Fetal_Growth_Restriction ("Deficient Uterine Spiral Artery Remodeling") and Placental_Abruption ("Decidual Vasculopathy and Spiral Artery Failure"). Brosens et al. also place preterm labor with intact membranes, preterm prelabor rupture of the membranes and late spontaneous abortion in the same group; the KB's Preterm_Premature_Rupture_of_the_Membranes entry currently models the amniochorion arm rather than the placental bed and so has no node to conform here yet. That is an open curation lead, not an omission from the module.
Three of the KB's obstetric entries were written independently and each named this same lesion differently - "Defective Trophoblast Invasion and Spiral Artery Remodeling", "Deficient Uterine Spiral Artery Remodeling", "Decidual Vasculopathy and Spiral Artery Failure". Fetal_Growth_Restriction's own notes record that it made no conforms_to declarations because no suitable module existed. That divergence is what this module exists to make checkable.
Decidualization Resistance at the Implantation Site
trigger
Endometrial stromal fibroblasts fail to complete the progesterone- and cAMP-driven differentiation into secretory decidual cells that normally prepares the implantation site. The undecidualized or partly decidualized stroma is the "soil" defect: decidual cells are what license, direct and ultimately limit extravillous trophoblast invasion, so a stroma that has not differentiated properly cannot support the invasion depth that deep placentation requires. In severe preeclampsia the defect is detectable in non-pregnant endometrium years after the affected pregnancy, which places it upstream of, and not merely consequent on, the abnormal placenta.
Downstream
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Shallow Extravillous Trophoblast Invasion of the Junctional Zone
A stroma that has not decidualized cannot guide extravillous trophoblast through the decidua into the junctional-zone myometrium.
Show evidence (2 references)
"Decidualization of endometrial cells regulates embryo invasion, which is essential for spiral artery remodeling and establishing the maternal-fetal interface."
States the module's premise that decidualization is the upstream control on the invasion that remodels the spiral arteries. Graded HUMAN_CLINICAL because the quoted sentence describes human endometrial and placental biology, with quote_role REVIEW_SYNTHESIS because the review is not where that finding was produced.
"ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE."
Measures the hormonal-signalling failure behind the decidualization defect in endometrial biopsies from women who had severe preeclampsia, which is what makes this node a distinct upstream step rather than a restatement of shallow invasion.
High-Momentum, Intermittent Uteroplacental Perfusion
effector
Blood reaches the intervillous space as a fast jet rather than a slow, steady stream, and because the retained smooth muscle leaves the vessel responsive to vasoconstrictors, delivery is intermittent. The placenta is therefore subjected to mechanical damage of the villous architecture and to repeated ischaemia-reperfusion rather than to steady hypoxia - a distinction that matters, because the two produce different cell-death phenotypes downstream.
Downstream
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Syncytiotrophoblast Oxidative Stress and Apoptosis
Repeated ischaemia-reperfusion generates reactive oxygen species in the syncytiotrophoblast, the layer in direct contact with maternal blood.
Show evidence (2 references)
"The retention of smooth muscle will also increase the risk of spontaneous vasoconstriction and ischaemia-reperfusion injury, generating oxidative stress."
Supplies the intermittency mechanism this node asserts. Marked INDIRECT because the authors state it as an inference from their model rather than as a measured result.
"We hypothesize that intermittent placental perfusion, secondary to deficient trophoblast invasion of the endometrial arteries, leads to an ischemia-reperfusion-type insult."
Records that this node is the hypothesis the downstream experiment was built to test, which is the honest grading - the sentence is the study's stated hypothesis, not its finding.
Syncytiotrophoblast Oxidative Stress and Apoptosis
effector
The syncytiotrophoblast, the multinucleate layer bathed in maternal blood, mounts an oxidative and hypoxic stress response and undergoes apoptotic change: mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage and nuclear condensation. This is the cellular step that converts a maternal vascular lesion into a placental secretory phenotype.
Downstream
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Release of Placental Factors into the Maternal Circulation
The stressed syncytiotrophoblast sheds antiangiogenic factors and apoptotic debris into maternal blood.
Show evidence (1 reference)
"After H/R, release of cytochrome c from mitochondria was significantly increased and was associated with intense immunolabeling for active caspase 3 in the syncytiotrophoblast and fetal endothelial cells."
Measures the apoptotic machinery in the specific cell type this node names, in human placental tissue subjected to hypoxia-reoxygenation.
Release of Placental Factors into the Maternal Circulation
consequence
The terminal, disorder-agnostic output of the module: the stressed placenta exports antiangiogenic factors - soluble fms-like tyrosine kinase 1 scavenging placental growth factor and VEGF - together with apoptotic debris, into the maternal circulation. What the mother and fetus then develop is decided by each conforming disorder and is deliberately not modelled here: preeclampsia continues into maternal endothelial dysfunction, fetal growth restriction into reduced transfer capacity and chronic fetal hypoxaemia, placental abruption into decidual haemorrhage and separation.
Show evidence (2 references)
"The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia."
Places the antiangiogenic export before clinical disease in a prospective human cohort, which is what makes this node a step in the chain rather than a marker of the outcome.
"Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant."
The dose-response the module predicts: the same placental export tracks both the early-onset preeclampsia phenotype and the growth-restricted one, which is the observation that makes a single shared upstream lesion plausible rather than two coincidental ones.