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Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

ABSTRACT: Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 knockout (Lrp4(-/-)) mice. Most Lrp4(-/-) foetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin-1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in Lrp4(-/-) foetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume.

SUBMITTER: Tanahashi H

PROVIDER: S-EPMC4742865 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

Tanahashi Hiroshi H Tian Qing-Bao QB Hara Yoshinobu Y Sakagami Hiroyuki H Endo Shogo S Suzuki Tatsuo T

Scientific reports 20160205

Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, whi ...[more]

PMID: 26847765

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Project description:BackgroundZika virus infection during pregnancy can cause serious birth defects, which include brain and eye abnormalities. The clinical importance of detection of Zika virus RNA in amniotic fluid is unknown.ObjectiveThe purpose of this study was to describe patterns of Zika virus RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between Zika virus detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that Zika virus detection in amniotic fluid was not associated with Zika-associated birth defects.Study designWe conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia's National Institute of Health as part of national Zika virus surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of Zika virus RNA with the use of a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher's exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of Zika virus RNA in amniotic fluid.ResultsOur analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally collected amniotic fluid; 42 women (33%) had amniotic fluid collected at delivery, and 11 women (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, which allowed for comparison across specimen types. Of those 91 women, 68 had evidence of Zika virus infection based on detection of Zika virus RNA in ≥1 specimen. Testing of amniotic fluid that was collected prenatally or at delivery identified 39 of these Zika virus infections (57%; 15 [22%] infections were identified only in amniotic fluid), and 29 infections (43%) were identified in other specimen types and not amniotic fluid. Among women who were included in the analysis, 89 had pregnancy outcome information available, which allowed for the assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (P<.05) more common among pregnancies with Zika virus RNA detected in amniotic fluid specimens collected prenatally (19/32 specimens; 59%) than for those with no laboratory evidence of Zika virus infection in any specimen (6/23 specimens; 26%), but the proportion was similar in pregnancies with only Zika virus RNA detected in specimens other than amniotic fluid (10/23 specimens; 43%). Although Zika-associated birth defects were more common among women with any Zika virus RNA detected in amniotic fluid specimens (ie, collected prenatally or at delivery; 21/43 specimens; 49%) than those with no laboratory evidence of Zika virus infection (6/23 specimens; 26%), this comparison did not reach statistical significance (P=.07).ConclusionTesting of amniotic fluid provided additional evidence for maternal diagnosis of Zika virus infection. Zika-associated birth defects were more common among women with Zika virus RNA that was detected in prenatal amniotic fluid specimens than women with no laboratory evidence of Zika virus infection, but similar to women with Zika virus RNA detected in other, nonamniotic fluid specimen types.

Project description:The existence of an amniotic fluid microbiota (i.e., a viable microbial community) in mammals is controversial. Its existence would require a fundamental reconsideration of fetal in utero exposure to and colonization by microorganisms and the role of intra-amniotic microorganisms in fetal immune development as well as in pregnancy outcomes. In this study, we determined whether the amniotic fluid of mice harbors a microbiota in late gestation. The profiles of the amniotic fluids of pups located proximally or distally to the cervix were characterized through quantitative real-time PCR, 16S rRNA gene sequencing, and culture (N = 21 dams). These profiles were compared to those of technical controls for bacterial and DNA contamination. The load of 16S rRNA genes in the amniotic fluid exceeded that in controls. Additionally, the 16S rRNA gene profiles of the amniotic fluid differed from those of controls, with Corynebacterium tuberculostearicum being differentially more abundant in amniotic fluid profiles; however, this bacterium was not cultured from amniotic fluid. Of the 42 attempted bacterial cultures of amniotic fluids, only one yielded bacterial growth - Lactobacillus murinus. The 16S rRNA gene of this common murine-associated bacterium was not detected in any amniotic fluid sample, suggesting it did not originate from the amniotic fluid. No differences in the 16S rRNA gene load, 16S rRNA gene profile, or bacterial culture were observed between the amniotic fluids located Proximally and distally to the cervix. Collectively, these data indicate that, although there is a modest DNA signal of bacteria in murine amniotic fluid, there is no evidence that this signal represents a viable microbiota. While this means that amniotic fluid is not a source of microorganisms for in utero colonization in mice, it may nevertheless contribute to fetal exposure to microbial components. The developmental consequences of this observation warrant further investigation.

Dataset Information

Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

Publications

Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

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