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Increased trophoblastic apoptosis mediated by neutrophil gelatinase-associated lipocalin (NGAL) activation in the nitrofen model of congenital diaphragmatic hernia

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Abstract

Background

Retinoids play a key role in fetal lung development. It has been suggested that the maternal–fetal retinol transport is disrupted by trophoblastic apoptosis. The mechanism underlying nitrofen-induced apoptosis in placenta is not fully understood. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in the fetal part of the maternal–fetal interface. NGAL is part of the immune barrier and serves primarily as a transport protein transferring biologically hazardous molecules in a safe and controlled way. It has been shown that over-activation of NGAL induces apoptosis. We hypothesized that increased placental NGAL expression induces trophoblastic apoptosis in the nitrofen model of CDH.

Methods

Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Placenta harvested on D21 and divided into two groups: control and nitrofen with CDH. Immunohistochemistry was performed to evaluate trophoblasts (by cytokeratin expression), NGAL expression, and apoptotic trophoblastic cells (using TUNEL assay). Total RNA was extracted from each placenta and the relative mRNA expression levels of NGAL were analyzed using RT-PCR.

Results

Immunohistochemistry showed NGAL immunoreactivity both in control and CDH in the fetal part of the fetal–maternal interface of placenta. Markedly increased NGAL expression was detected in CDH group compared to controls. Relative mRNA expression levels of NGAL gene were significantly increased in the CDH group compared to control in the placenta (5.924 ± 0.93 vs. 1.895 ± 0.54, p < 0.001). Markedly increased numbers of apoptotic trophoblastic cells were seen in the maternal–fetal interface in the CDH group compared to controls.

Conclusions

NGAL activation may lead to increased trophoblastic apoptosis in the maternal–fetal interface in the nitrofen model of CDH. These changes may therefore cause disturbance in maternal–fetal retinol transport affecting fetal lung morphogenesis.

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Authors and Affiliations

  1. The National Children’s Research Center, Our Lady’s Children’s Hospital, Crumlin, Dublin, 12, Ireland

    Balazs Kutasy, Jan H. Gosemann, Johannes W. Duess & Prem Puri

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  1. Balazs Kutasy
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  2. Jan H. Gosemann
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  3. Johannes W. Duess
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  4. Prem Puri
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Correspondence to Prem Puri.

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Kutasy, B., Gosemann, J.H., Duess, J.W. et al. Increased trophoblastic apoptosis mediated by neutrophil gelatinase-associated lipocalin (NGAL) activation in the nitrofen model of congenital diaphragmatic hernia. Pediatr Surg Int 29, 25–31 (2013). https://doi.org/10.1007/s00383-012-3203-6

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