RESUMO
Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.
Assuntos
Maturidade dos Órgãos Fetais/efeitos dos fármacos , Feto/metabolismo , Hérnias Diafragmáticas Congênitas , Efeitos Tardios da Exposição Pré-Natal , Tretinoína/farmacologia , Vitaminas/farmacologia , Animais , Western Blotting , Caveolina 1/genética , Caveolina 1/metabolismo , Morte Celular , Feminino , Hérnia Diafragmática/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Pulmão/fisiopatologia , Modelos Animais , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína A Associada a Surfactante Pulmonar/genética , Proteína B Associada a Surfactante Pulmonar/genética , Proteína B Associada a Surfactante Pulmonar/metabolismo , Proteína C Associada a Surfactante Pulmonar/genética , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Today, modern ultrasound equipment and the wide implementation of screening programmes allow the timely diagnosis of many congenital anomalies. For some of these, fetal surgery may be a life-saving option. In Europe, open fetal surgery became poorly accepted because of its invasiveness and the high incidence of postoperative premature labour and rupture of the fetal membranes. In the 1990s, the merger of fetoscopy and advanced video-endoscopic surgery formed the basis for endoscopic fetal surgery. We review the current applications of fetal surgery via both methods of access. The first clinical fetoscopic surgeries were interventions on the umbilical cord and the placenta, often referred to as obstetrical endoscopy. The outcome of a randomized clinical trial demonstrating that fetoscopic laser coagulation of chorionic plate vessels is the most effective treatment for twin-twin transfusion syndrome (TTTS) has revived interest in endoscopic fetal therapy. Operating on the fetus is another more challenging enterprise. Clinical fetal surgery programmes were virtually non-existent in Europe until minimally invasive fetoscopic surgery made such operations clinically possible as well as maternally acceptable. At present, most experience has been gathered with fetal tracheal occlusion as a therapy for severe congenital diaphragmatic hernia. As in other fields, minimally invasive surgery has pushed back boundaries and now allows safe operations to be performed on the fetal patient. Whereas minimal access seems to solve the problem of preterm labour, all procedures remain invasive, and carry a risk to the mother and a substantial risk of preterm prelabour rupture of the membranes (PPROM). The latter problem may prove to be a bottleneck for further developments, although treatment modalities are currently being evaluated.