Relaxin, Its Receptor (RXFP1), and Insulin-Like Peptide 4 Expression Through Gestation and in Placenta Accreta

Abstract

This study was designed to show whether placental relaxin (RLN), its receptor (RXFP1), or insulin-like peptide 4 (INSL4) might have altered expression in patients with placenta accreta. The baseline expression of their genes through gestation (n ¼ 34) was quantitated in the placental basal plate (BP) and villous trophoblast (TR), and compared to their expression in placenta accreta (n ¼ 6). The proteins were also immunolocalized and quantitated in the accreta tissues. The messenger RNAs (mRNAs) of matrix metalloproteinase 9, -2, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were also measured. Results demonstrated that the BP and TR expressed low levels of RLN/RXFP1 and INSL4 through gestation. In accreta, increased RLN gene and protein in BP were associated with antepartum bleeding whereas INSL4 expression decreased throughout the TR. There were no changes in mRNAs for MMPs, but TIMP-1 was increased only in the invasive TR.

Placenta Accreta Spectrum: A Review of Pathology, Molecular Biology, and Biomarkers

“…Placental relaxin (RLN) and its receptor (RXFPI) play an important role in angiogenesis in the endometrium by stimulating expression of VEGF [ 24 ]. Increased expression of RLN gene and protein has been demonstrated in the PAS basal plate, while the receptor RFXP1 is overexpressed in both the basal plate and villous trophoblast in PAS specimens compared to controls suggesting that PAS may produce a number of autocrine and paracrine factors that promote the upregulation of angiogenic-stimulating factors combined with a suppression in antiangiogenic factors leading to extensive neovascularisation [ 25 ].…”

“…Insulin-like protein 4 (INSL4), produced by the placenta, plays an important role in the inhibition of excessive placental proliferation by inducing apoptosis [ 30 ]. Decreased INSL4 gene expression in both the invasive and the noninvasive areas of extravillous trophoblasts has been demonstrated in patients with PAS when compared to gestational age-matched controls suggesting that abnormal invasion is a more generalized process due to the failure of normal apoptosis [ 25 ].…”

Relaxin and insulin‐like peptide 3 in the musculoskeletal system: from bench to bedside

“…Major clinical issues arise from the physiological roles of these two members of the relaxin‐related peptide family in the musculoskeletal system. Relaxin is mainly released by the corpus luteum and the placenta, thus it is essentially engaged during growth, pregnancy and parturition in different species of mammals (Goh et al , ). Therefore, on the one hand, it is unlikely that this peptide has a physiological role in the musculoskeletal system far from the gestational scenario.…”

Placenta accreta: diagnosis, management and the molecular biology of the morbidly adherent placenta

“…(30) Goh et al showed by gene expression and immunohistochemistry that INSL4 expression was significantly decreased in trophoblastic tissue in both invasive and non invasive areas in placenta accreta when compared to gestational aged matched controls. They suggest that accreta formation is not a local trophoblastic problem but a more generalized phenomenon and that the pathophysiology of trophoblastic invasiveness is related to reduced trophoblast apoptosis (31). This group also showed that increased Relaxin gene and protein expression was associated with significant antepartum bleeding in accreta patients.…”