Placenta

Title Page/Editorial Board

2012-02-01

Effects of iron deficiency anemia and its treatment with iron polymaltose complex in pregnant rats, their fetuses and placentas: Oxidative stress markers and pregnancy outcome

J.E. Toblli, G. Cao, L. Oliveri, M. Angerosa — 2011-12-09

Abstract: Objective: Iron deficiency anemia (IDA) can severely impair the outcome of pregnancy. IDA has been shown to cause oxidative stress, which may be exacerbated by oral iron therapy. In this study, the effects of IDA and its treatment with iron polymaltose complex/folic acid (IPC/FA) were examined in anemic pregnant rats, their fetuses and placentas.Study design: Hematological variables and oxidative stress markers in the liver, heart and kidney were evaluated in non-anemic, anemic and IPC/FA-treated pregnant rats and their fetuses. Markers for oxidative stress, inflammation and hypoxia were assessed in the placentas of all groups.Results: IDA was shown to increase oxidative stress levels in all the studied organs and in placenta as well as hypoxia and inflammation in placenta. IPC/FA treatment corrected IDA measured by the hemoglobin level, serum iron level and transferrin saturation. The oxidative stress levels in all the studied organs and in placentas of the IPC/FA-treated group were comparable to those of the non-anemic group. The number of fetuses and the neonatal and placental weight were lower in the anemic group compared to the non-anemic and IPC/FA-treated groups.Conclusions: The current study shows that IDA in pregnant rats impaired pregnancy outcome, increased the expression of hypoxia and inflammatory markers in the placenta, and increased oxidative stress in dams, fetuses and placentas. Treatment with oral IPC/FA corrected the IDA as well as reduced the levels of oxidative stress and inflammatory markers close to non-anemic control values in all the studied organs.

The contribution of apoptosis-inducing factor (AIF) to villous trophoblast differentiation

M.R. Riddell, B. Winkler-Lowen, L.J. Guilbert — 2011-12-02

Abstract: Apoptosis is postulated to be a delayed but important part of the differentiation of placental villous cytotrophoblasts (CT) into functional syncytiotrophoblast (ST). This hypothesis is based on the observation that the externalization of phosphatidylserine and the activation of caspase 8 are required for trophoblast differentiation. In contradiction to this hypothesis we have previously found that differentiation occurs in the presence of both broad spectrum and caspase 8 specific inhibitors. Apoptosis-inducing factor (AIF) is a mitochondria-associated protein which is known to translocate to the nucleus and induce caspase-independent nuclear condensation, phosphatidylserine externalization and cell death. Thus AIF nuclear translocation may result in the apoptotic-like features associated with trophoblast differentiation and may be an obligatory event for differentiation to proceed. AIF translocation was assessed in isolated primary trophoblasts by optical section microscopy of antibody stained cells. We found AIF to be strongly expressed in the villous trophoblast and that small amounts of AIF were localized to the nucleus of the cells. Significantly, inhibitors of AIF translocation (calpeptin and zFA-fmk) blocked translocation but not differentiation of the cells. We conclude that AIF translocation is not involved in CT differentiation in isolated cell culture.

Ontogeny of growth-regulating genes in the placenta

N. Kumar, J. Leverence, D. Bick, V. Sampath — 2011-12-12

Abstract: Background: Placental nutrient flow is the primary determinant of fetal growth. This key function of the placenta depends on several growth-promoting or -suppressing imprinted genes including Insulin-like growth factor [IGF] axis genes, which regulate nutrient transfer across the placenta. However whether changes in the placental expression of these genes parallel increased fetal growth observed in the second and third trimester remains unknown.Objective: The aim of our study was to determine the ontogeny of key IGF axis genes and other growth regulating imprinted genes in the placenta and to characterize patterns of placental gene expression associated with intrauterine growth restriction (IUGR).Study design: Real time RT-PCR analysis of 11 genes using specific probes were performed in the placental tissue collected at the time of delivery from 63 subjects with live birth pregnancies from 24 to 40 weeks gestation between 2009 -2010.Results: We found that paternally expressed gene ZNF127 (p < 0.001) was upregulated whereas IGF1 (p = 0.001) and maternally expressed gene PHLDA2 (p = 0.001) were downregulated with advancing gestational age. ROC analysis revealed a significant change in the expression of the above genes early in the third trimester. When compared to age-matched appropriate for gestational age (AGA) infants, expression of PHLDA2 (p = 0.03) IGF2R (p < 0.05) was upregulated in IUGR infants. Maternal age was also a significant predictor for IUGR (p = 0.05).Conclusion: We found increased placental expression of growth-promoting imprinted genes and decreased expression of growth-suppressive imprinted genes with advancing gestational age. These changes in placental gene expression could potentially explain accelerated fetal growth seen in the third trimester. Upregulation of maternally expressed imprinted genes in IUGR population supports the “parental conflict hypothesis”.

Circulating and utero-placental adaptations to chronic placental ischemia in the rat

J.S. Gilbert, A.J. Bauer, A. Gingery, C.T. Banek, S. Chasson — 2011-12-21

Abstract: While utero-placental insufficiency is associated with adverse outcomes for both mother and fetus, many of the maternal-fetal adaptations during pregnancy in models of fetal compromise remain unclear. The purpose of this study was to determine if chronically reduced uterine perfusion pressure (RUPP) during days 14–19 of gestation alters feto-placental growth differentially from the cervical to ovarian ends of the uterus and generates metabolic adaptations such as increased blood lactate (BLa) concentrations and lactate transporter expression in the placenta. Fetal growth restriction was evident, placental efficiency (fetal weight/placental weight) decreased (4.7 ± 0.35 vs. 5.9 ± 0.30; P < 0.05) and fetal growth pattern within the uterus was altered in the RUPP compared to the normal pregnant (NP) rats. Blood lactate concentrations were increased (3.3 ± 0.3 vs. 2.1 ± 0.4 mmol/l; P < 0.05) in NP compared to virgin rats, and in RUPP compared to NP (5.0 ± 0.6 vs. 3.3 ± 0.3 mmol/l; P < 0.05). Lactate concentration was increased (10.0 ± 0.6 vs. 7.1 ± 0.8 mmol/l; P < 0.05) in the media from hypoxic compared to normoxic BeWo cells. No changes in expression of placental MCT1, 2, or 4 were observed between RUPP and NP rats. RUPP resulted in decreased plasma leptin (2.0 ± 0.3 vs. 3.1 ± 0.4; P < 0.05) but no change in IGF-1 compared to NP. The present data indicate chronic placental ischemia results in numerous endocrine and metabolic changes during late pregnancy in the rat and that the RUPP model has differential effects on fetal growth depending on uterine position.

Twelve oxo-eicosatetraenoic acid induces fetal membrane release after delivery in cows

2011-11-28

Abstract: Fetal fibroblast cell culture from cotyledons of bovine placenta and animal experiments close to term were used to elucidate afterbirth release and factors missing in the signal transduction mechanism for retained fetal membranes (RFM) after delivery. In cell culture the addition of arachidonic acid (Ara) to the medium caused rapid release to free floating cell in the culture dish, accompanied by matrix metalloproteinase (MMP) activation, being consistent with previous in vivo observations, where a relation between MMP and fetal membrane release had been shown. Ara-induced cell floating was not inhibited by the addition of cyclooxygenase (COX) inhibitor, and not induced by the addition of PGF2α or PGE2 to replace Ara, while 12-lipoxygenase (12-LOX) metabolite of Ara, 12-oxo-eicosatetraenoic acid (12-oxoETE), strongly induced cell floating. In the animal experiments, 12-oxoETE injection to delivery-induced cows (n = 6) using prostaglandin (PG) and dexamethazone resulted in rapid release of fetal membranes. In cows with natural calf delivery, a 12-oxoETE peak (11.7–16.8 ng/ml) was observed in maternal blood plasma prior to release of fetal membranes. This investigation thus gives new indications for that the mediator for fetal membrane release is 12-oxoETE and not PG.

Decreasing maternal nutrient intake during the final third of pregnancy in previously overnourished adolescent sheep: Effects on maternal nutrient partitioning and feto-placental development

2011-12-12

Abstract: When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and ∼20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation.

Cryopreservation of placental biopsies for mitochondrial respiratory analysis

F. Colleoni, A.J. Morash, T. Ashmore, M. Monk, G.J. Burton, A.J. Murray — 2011-12-12

Abstract: Mitochondrial function is required to support energetically-demanding processes in the placenta. As such, a compromise in mitochondrial function could severely impact fetal growth and development. Respirometry is a highly useful method for studying mitochondrial function, but is not possible in freeze-thawed mitochondria, which become uncoupled. We have developed a novel method that permits respiratory analysis of cryopreserved placental tissue. We studied mitochondrial function in 7 normal human placentas, analysing both fresh and cryopreserved samples. We found no impairments in respiration following cryopreservation in the delivery suite, with enhanced coupling, as indicated by higher respiratory control ratios, than in fresh placental samples transported to the laboratory on ice.

Impact of genetic background on placental glycogen storage in mice

S.J. Tunster, M. Van de Pette, R.M. John — 2011-12-09

Abstract: 129 and C57BL/6 are two of the most widely used laboratory mouse strains. While it is well known that genetic modifiers between the two strains can directly influence embryonic and adult phenotypes, less is known regarding morphological differences in placental development. Here we identify differences in the junctional zone, glycogen storage and the maternal-fetal interface between these two strains and provide examples where these differences impact the phenotypic characterisation of placental mutations.

Placental histopathology after Coxiella burnetii infection during pregnancy

2011-12-06

Abstract: Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C. burnetii infection during pregnancy and compared these cases with four symptomatic cases from the literature. In contrast with the symptomatic cases, we did not observe necrosis or active inflammation in the placentas of the asymptomatic women. Obstetrical outcome was more favourable in the asymptomatic cases than in the symptomatic cases. Asymptomatic and symptomatic C. burnetii infection during pregnancy are different entities with respect to placental histopathology and the risk of obstetric complications.

Decreased mitochondrial fatty acid oxidation in placentas from women with preeclampsia

J.L. Bartha, F. Visiedo, A. Fernández-Deudero, F. Bugatto, G. Perdomo — 2011-12-22

Abstract: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in high and low-income countries. The aetiology of preeclampsia is multifactorial and remains obscure. Some evidences suggest that altered placental fatty acid oxidation might play a role in the pathogenesis of preeclampsia. To reveal if placental fatty acid oxidation is reduced in preeclampsia, we evaluate the expression levels of enzymes of mitochondrial fatty acid oxidation using quantitative Real-time PCR and the fatty acid oxidation rate in placental explants. We found that long-chain 3-hydroxyacyl-CoA dehydrogenase levels and fatty acid oxidation capacity were significantly reduced in placentas from women with preeclampsia.

The early determination of circulating TRAIL levels does not predict the development of pre-eclampsia

G. Zauli, L. Monasta, L. Vecchi Brumatti, L. Ronfani, G. D'ottavio, P. Secchiero — 2011-12-12

TRAIL is a pleiotropic cytokine, showing important regulatory activities in the immune and cardiovascular systems . Among different tissues, TRAIL is expressed by placenta and can up-regulated in trophoblast cells after cytokine stimulation . Since previous studies from our and other groups have demonstrated that the serum levels of TRAIL are significantly decreased in patients affected by cardiovascular disease , we have carried out a case-control study aimed at evaluating the potential predictive role of first trimester TRAIL (12 weeks of gestational age) as a risk factor for hypertensive pregnancy disorders (HD: gestational hypertension or pre-eclampsia) and diabetes (gestational or IDDM). For each case of HD and diabetes, three controls were randomly selected matched to cases for age (exact age in years, ±2 years if controls of exact age were unavailable), parity (primiparous; multiparous) and pregestational BMI (1. bmi = 30) (). We found no significant differences between both groups of cases and controls in terms of circulating TRAIL values (pg/ml) (non-parametric Mann–Whitney U test as TRAIL values did not distribute normally: for HD p = 0.76, for diabetes p = 0.59). Finally, none of the correlations between TRAIL values and mean pulsatility index, mean resistance index, bilateral notch at 12 weeks gestation, 20 and 30 weeks gestation was significant. Thus, although TRAIL has different functions at the placenta level, including a placental protective role , we did not find any statistically significant difference in the levels of circulating TRAIL at 12 gestational weeks between HD or diabetic and control women, indicating that TRAIL may not be a good candidate as a biomarker to evaluate early-stage lesions associated to pre-eclampsia.

IFPA Pages

2012-02-01