Steady-state levels of aquaporin 1 mRNA expression are increased in idiopathic polyhydramnios.

OBJECTIVE: Polyhydramnios is a condition associated with significant perinatal morbidity. While the exact pathophysiology of this condition is unknown in the absence of obvious anatomic or organic etiologies, impaired intramembranous water transport has been shown. Previous studies from our laboratory have shown that the water channel aquaporin 1 (AQP1) is expressed in human fetal membranes from term pregnancies with normal amniotic fluid (AF) volume. Therefore, we hypothesized that in pregnancies with idiopathic polyhydramnios, AQP1 expression might be reduced in fetal membranes from pregnancies with this AF volume disorder. STUDY DESIGN: Placentas were collected from women at term (37-40 weeks) who presented with either polyhydramnios (amniotic fluid index [AFI] >24.0 cm) or normal AF volume (AFI 5.0-23.9 cm). Immediately after delivery, the membranes (amnion and chorion) directly overlying the placenta and the free-floating reflected membranes were sampled (total of 4 samples from each placenta). RNA was isolated from each sample and expression was quantified using real-time reverse transcriptase polymerase chain reaction (PCR) and relative quantification of gene expression. RESULTS: Relative to pregnancies with normal AF volume, there was an increase in expression of the water channel AQP1 in all regions of the fetal membranes. The greatest increase (33-fold) was seen in the reflected amnion. CONCLUSION: AQP1 expression is increased in polyhydramnios. This finding suggests that alterations in AQP1 expression may be a compensatory response to and not a cause of idiopathic polyhydramnios. We speculate that therapies focused on regulating AQP1 expression may be useful for treating this condition.

Perivascular Adipose Tissue: A Novel Regulator of Vascular Tone in the Rat Pregnancy.

Perivascular adipose tissue (PVAT) contributes to vasoregulation. The role of this adipose tissue bed in pregnancy has not been examined. Here, we tested the hypothesis that PVAT in pregnant rats decreases resistance artery tone. Mesenteric arteries from nonpregnant (NP) and late pregnant (LP) rats were exposed to phenylephrine (PHE) or KCl in the presence (+) versus absence (-) of PVAT. The LP PVAT(+) vessels showed a 44% decrease in sensitivity to PHE in the presence of PVAT. There was no attenuation of the contractile response to KCl when PVAT was present. The LP arteries perfused with LP or NP PVAT underwent vasodilation; unexpectedly, NP vessels in the presence of PVAT from LP rats sustained a 48% vasoconstriction. The PVAT attenuates vasoconstriction by a mechanism that involves hyperpolarization. The vasoconstriction observed when nonpregnant vessels were exposed to pregnant PVAT suggests pregnant vessels adapt to the vasoconstricting influence of pregnant PVAT.

Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

UNLABELLED: Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. OBJECTIVE: The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. METHODS: Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. RESULTS: At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. CONCLUSION: This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background.

A novel model of polyhydramnios: amniotic fluid volume is increased in aquaporin 1 knockout mice.

OBJECTIVE: To test the hypothesis that amniotic fluid volume is increased in aquaporin 1 knockout mice. STUDY DESIGN: Transgenic mice deficient in aquaporin 1 protein were generated by targeted gene disruption, as described previously. After a cesarean section was performed, intact, individual gestational sacs were removed from the uterus and weighed. Amniotic fluid volume, osmolality, and fetal and placental weights were determined. Data were analyzed by a 1-way analysis of variance for ranks; Dunn's post hoc test was used to analyze significant trends. RESULTS: Analysis of 16 litters showed 35 wild-type, 52 heterozygote, and 33 aquaporin 1 knockout mice. The knockout mice had a greater volume of amniotic fluid and lower amniotic fluid osmolality than their wild-type and heterozygote counterparts. There were no significant differences in fetal or placental weights among the groups. CONCLUSIONS: Aquaporin 1 null fetuses produce a greater volume of more dilute amniotic fluid. Our findings show that aquaporin 1 water channels in fetal membranes may contribute to amniotic fluid volume regulation. We speculate that idiopathic polyhydramnios may be associated with a deficiency of aquaporin 1 channels in human fetal membranes. Transgenic aquaporin 1 knockout mice provide a unique animal of polyhydramnios.

Expression and localization of aquaporin 1 and 3 in human fetal membranes.

OBJECTIVES: Aquaporins are a family of water-selective channels that facilitate fluid movement across cell membranes. Specifically, aquaporin 1 (AQP1) and aquaporin 3 (AQP3) have been found to be important in osmotic water movement across membranes. Our goal in this study was (1) to determine whether AQP1 or AQP3 messenger RNA are expressed in the chorioamniotic membrane and, if present, (2) to determine the precise membrane location of these aquaporins. STUDY DESIGN: Placentas were collected from women with intact membranes not in labor who underwent elective cesarean sections at term (37-40 weeks). The membranes (amnion and chorion) directly overlying the placenta were sampled as well as the free-floating reflected membranes. RNA and protein were isolated from the amnion and chorion. Reverse transcriptase-polymerase chain reaction, Western analysis, and immunohistochemistry were used to determine expression and localization of AQP1 and AQP3. RESULTS: AQP1 messenger RNA was found in amnion and chorion from both membrane locations. Western analysis also yielded positive results for amnion and chorion from both locations. Immunohistochemical localization of AQP1 showed it to be present on the apical aspect of the chorionic plate amnion. AQP3 protein was not found in the fetal membranes. CONCLUSIONS: AQP1 is present in the fetal membranes. AQP1 may play a role in water movement from the amniotic cavity across the placenta into the fetal circulation. Further studies are needed to clarify our understanding of the role of fetal membrane aquaporins in amniotic fluid homeostasis.