P-424 Placental extracellular matrix remodelling in pregnancies by oocyte donation shows similarities with preeclamptic placenta: a pilot study
Authors: Andreuzzi E , Toffoli M , Zito G , Balduit A , Luppi S , Bottega R , De Rocco D , Martinelli M , Giolo E , Skerk K , Mongiat M , Stampalija T , Agostinis C , Bulla R , Ricci G 
Published: July 2024

Abstract

Study question
Do stromal alterations occur during placentation upon heterologous assisted reproductive techniques (ART) and are they associated with a higher risk of developing preeclampsia?

Summary answer
The remodelling of extracellular matrix molecules, key for vascularization and immunity, is altered in pregnancies from oocyte donation and resembles the miss-regulations observed in preeclampsia.

What is known already
Preeclampsia represents one of the main causes of maternal and perinatal morbidity, affecting 2-8% of spontaneous pregnancies. Its incidence increases two times upon homologous ART and up to four times upon oocyte donation, however the underlying factors are still unknown. Preeclampsia is characterized by high blood pressure and endothelial cell dysfunction, but its pathogenesis is multifactorial relying on vascular, metabolic and immune alterations. All these elements are tightly influenced by the extracellular matrix (ECM) that, during an uneventful pregnancy, is remodelled to support an efficient placentation and immunotolerance. Despite its key functions, little is known regarding ECM remodelling in preeclampsia.

Study design, size, duration
This is an observational pilot study conducted over a 12 months period. Four groups were included: 1) pregnant women that underwent homologous ART (n = 7; HOM); 2) pregnant women that underwent oocyte donation (n = 10; OD); 3) women that conceived spontaneously affected by PE (n = 7); and 4) uneventful spontaneous pregnancies (n = 8; control group CTRL).

Participants/materials, setting, methods
For each patient placental samples have been collected upon delivery and processed to perform molecular and proteomic analysis by real time PCR and immunohistochemistry The statistical differences among the groups have been evaluated by the ANOVA and Mann-Whitney tests.

Main results and the role of chance
We focused our study on specific ECM elements known to modulate angiogenesis and immunity, two key players in preeclampsia occurrence. Our data indicated first that collagen I, collagen IV and Multimerin-2, important components of the vessel wall that contribute to vessel stabilization and efficiency, are significantly decreased in OD compared to HOM group (coll I P = 0.04; coll IV P = 0.043; Multimerin-2 P = 0.036). Next, we analyzed EMILIN-2 and versican, two ECM components exerting not only angiogenic but also immunomodulatory functions. We found that EMILIN-2 is decreased in OD compared to CTRL placentas (P = 0.043), whereas versican undergoes an opposite regulation, being slightly increased in the OD placentas (P = 0.045). We observed an analogous mis-regulation when comparing PE to the CTRL group, suggesting that these stromal alterations may take part in the establishment of a microenvironment more prone to preeclampsia onset and associate with the higher risk related to OD pregnancies. We also found that some features of ECM remodelling seem to be strongly associated with OD. Precisely, our data denoted that the glycoprotein tenascin-C decreased specifically in OD patients, while was comparable between HOM, PE and CTRL groups (P = 0.042).

Limitations, reasons for caution
The main limitation of this pilot study is the restricted number of patients. Further investigations on a larger sample and prospective cohort of patients might provide more robust data.

Wider implications of the findings
Our data highlighted for the first time that the placental stroma undergoes an altered remodelling in OD and PE pregnancies. We envision that a deep characterization of ECM will help better understanding of the mechanisms behind the pathogenesis of preeclampsia with possible implications for prediction and prevention.

Trial registration number
N/A