Browsing by Autor "Lourdes Echalar"

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Additional data on Trypanosoma cruzi isozymic strains encountered in Bolivian domestic transmission cycles
(Oxford University Press, 1986) Michel Tibayrenc; Ary A. Hoffmann; Olivier Poch; Lourdes Echalar; François Le Pont; Jean-Loup Lemesre; P. Desjeux; Francisco J. Ayala
We have collected in Bolivia 212 stocks of Trypanosoma cruzi from domestic transmission cycles and have assayed for nine enzyme systems (11 gene loci). Only a few different isozyme profiles exist, without recombination between them, a situation also encountered in previous Bolivian samples. The 212 stocks, combined with 207 stocks previously studied, have been analysed to uncover any spatial patterns. The frequency of heterozygous strains (2 and 2a) decreases westwards and with increasing altitude. Given that longitude and altitude are correlated with each other, it is not possible to decide which of these two geographic variables is the relevant one, or if both are. These associations might be due to climatic factors. Studies by other authors have shown, however, that heterozygous strains are rare or absent in the Amazon Basin, which is at low altitude.
Ancestry dependent balancing selection of placental dysferlin at high-altitude
(Frontiers Media, 2023) William E. Gundling; Sasha Post; Nicholas P. Illsley; Lourdes Echalar; Stacy Zamudio; Derek E. Wildman
Introduction: The placenta mediates fetal growth by regulating gas and nutrient exchange between the mother and the fetus. The cell type in the placenta where this nutrient exchange occurs is called the syncytiotrophoblast, which is the barrier between the fetal and maternal blood. Residence at high-altitude is strongly associated with reduced 3rd trimester fetal growth and increased rates of complications such as preeclampsia. We asked whether altitude and/or ancestry-related placental gene expression contributes to differential fetal growth under high-altitude conditions, as native populations have greater fetal growth than migrants to high-altitude. Methods: We have previously shown that methylation differences largely accounted for altitude-associated differences in placental gene expression that favor improved fetal growth among high-altitude natives. We tested for differences in DNA methylation between Andean and European placental samples from Bolivia [La Paz (∼3,600 m) and Santa Cruz, Bolivia (∼400 m)]. One group of genes showing significant altitude-related differences are those involved in cell fusion and membrane repair in the syncytiotrophoblast. Dysferlin (DYSF) shows greater expression levels in high- vs. low-altitude placentas, regardless of ancestry. DYSF has a single nucleotide variant (rs10166384;G/A) located at a methylation site that can potentially stimulate or repress DYSF expression. Following up with individual DNA genotyping in an expanded sample size, we observed three classes of DNA methylation that corresponded to individual genotypes of rs10166384 (A/A < A/G < G/G). We tested whether these genotypes are under Darwinian selection pressure by sequencing a ∼2.5 kb fragment including the DYSF variants from 96 Bolivian samples and compared them to data from the 1000 genomes project. Results: We found that balancing selection (Tajima's D = 2.37) was acting on this fragment among Andeans regardless of altitude, and in Europeans at high-altitude (Tajima's D = 1.85). Discussion: This supports that balancing selection acting on dysferlin is capable of altering DNA methylation patterns based on environmental exposure to high-altitude hypoxia. This finding is analogous to balancing selection seen frequency-dependent selection, implying both alleles are advantageous in different ways depending on environmental circumstances. Preservation of the adenine (A) and guanine (G) alleles may therefore aid both Andeans and Europeans in an altitude dependent fashion.
DNA Methylation Explains a Subset of Placental Gene Expression Differences Based on Ancestry and Altitude
(2018) William E. Gundling; Priyadarshini Pantham; Nicholas P. Illsley; Lourdes Echalar; Stacy Zamudio; Derek E. Wildman
Abstract: Objectives : The most pronounced effect of high altitude (>2700m) on reproductive outcomes is reduced birth weight. Indigenous Bolivians (Andean Native Americans) residing for generations at high altitudes have higher birth weights relative to more recent migrants of primarily European ancestry. Previous research demonstrated that the placenta is a key contributor to the preservation of Andean birth weight at high altitude. Our current research investigated how gene expression and epigenetics contributes to the conservation of birth weight at high altitude by examining mRNA expression and DNA methylation differences between placentas of Andeans and those of European ancestry residing at high and low altitude. Methods : Genome-wide mRNA expression and DNA methylation of villous placenta tissue was quantified utilizing microarray technology. Subjects were of Andean and European ancestry and resident at high (3600m) or low (400m) altitudes. Differentially expressed genes (DEGs) associated with altitude or ancestry were identified (FDR<0.1, |fold change|>1.25). To predict which DEGs could be regulated by methylation we tested for correlation between gene expression and methylation values. Results : 69 DEGs associated with altitude (n=36) or ancestry (n=34) were identified. Altitude-associated DEGs included members of the AP-1 transcription factor family. Ancestry-associated DEGs were implicated in inflammatory pathways and associated with pro-angiogenic macrophages. More ancestry-associated DEGs correlated significantly (n=17) (FDR<0.1) with promoter or gene body methylation (p=0.0242) when compared to altitude associated DEGs (n=8). Conclusions: Compared to altitude-associated DEGs, methylation regulates more ancestry-associated DEGs, potentially allowing for rapid modification in the expression of inflammatory genes to attract pro-angiogenic macrophages as a means of promoting placental capillary growth in Andeans, regardless of altitude.
Evidence for extraplacental sources of circulating angiogenic growth effectors in human pregnancy
(Elsevier BV, 2013) Stacy Zamudio; Olga Kovalenko; Lourdes Echalar; Tatiana Torricos; Abdulla Al‐Khan; Marina Álvarez Benito; Nicholas P. Illsley
Gene Expression Differences Reveal Ancestry-Specific Environmental Interactions in Placental Adaption to High-Altitude Hypoxia
(Elsevier BV, 2013) William E. Gundling; Stacy Zamudio; Nicholas P. Illsley; Lourdes Echalar; Derek E. Wildman
Human adaptation to high altitude via tripartite methylation at an intronic CACNA1C CpG-SNP in the placenta
(Elsevier BV, 2023) Sasha Post; William E. Gundling; Nicholas P. Illsley; Jan Dahrendorff; Lourdes Echalar; Stacy Zamudio; Derek E. Wildman
Hypoglycemia and the Origin of Hypoxia-Induced Reduction in Human Fetal Growth
(Public Library of Science, 2009) Stacy Zamudio; Tatiana Torricos; Ewa Fik; Maria Oyala; Lourdes Echalar; Janet Pullockaran; Emily Tutino; Brittney Martin; Sonia Belliappa; Elfride Balanza
Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that placentally-mediated reduction in glucose transport is an initiating factor for reduced fetal growth under conditions of chronic hypoxemia.
Maternal and Fetoplacental Hypoxia Do Not Alter Circulating Angiogenic Growth Effectors During Human Pregnancy1
(Oxford University Press, 2013) Stacy Zamudio; Marcus Borges; Lourdes Echalar; Olga Kovalenko; Enrique Vargas; Tatiana Torricos; Abdulla Al Khan; Manuel Alvarez; Nicholas P. Illsley
One causal model of preeclampsia (PE) postulates that placental hypoxia alters the production of angiogenic growth effectors (AGEs), causing an imbalance leading to maternal endothelial cell dysfunction. We tested this model using the natural experiment of high-altitude (HA) residence. We hypothesized that in HA pregnancies 1) circulating soluble fms-like tyrosine kinase 1 (sFlt-1) is increased and placental growth factor (PlGF) decreased, and 2) AGE concentrations correlate with measures of hypoxia. A cross-sectional study of healthy pregnancies at low altitude (LA) (400 m) versus HA (3600 m) compared normal (n = 80 at HA, n = 90 at LA) and PE pregnancies (n = 20 PE at HA, n = 19 PE at LA). Blood was collected using standard serum separation and, in parallel, by a method designed to inhibit platelet activation. AGEs were measured by enzyme-linked immunosorbent assays. AGEs did not differ between altitudes in normal or PE pregnancies. AGE concentrations were unrelated to measures of maternal or fetal hypoxia. PlGF was lower and sFlt-1 higher in PE, but overlapped considerably with the range observed in normal samples. PlGF correlated with placental mass in both normal and PE pregnancies. The contribution of peripheral cells to the values measured for AGEs was similar at LA and HA, but was greater in PE than in normotensive women. Hypoxia, across a wide physiological range in pregnancy, does not alter levels of circulating AGEs in otherwise normal pregnancies. Peripheral cell release of AGEs with the hemostasis characteristic of standard blood collection is highly variable and contributes to a doubling of the amount of sFlt-1 measured in PE as compared to normal pregnancies.
Maternal oxygen delivery is not related to altitude‐ and ancestry‐associated differences in human fetal growth
(Wiley, 2007) Stacy Zamudio; Lucrecia Postigo; Nicholas P. Illsley; Carmelo Rodriguez; Gladys Heredia; Michael Brimacombe; Lourdes Echalar; Tatiana Torricos; Wilma Téllez; Iván Maldonado
Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O(2) delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n=180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphism. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P<0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O(2) delivery regardless of ancestry. But the hypothesis was rejected as O(2) delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O(2) delivery, regardless of altitude (P<0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P<0.01), but admixture was not related to any of the O(2) transport variables. Genetically mediated differences in maternal O(2) delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O(2) and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O(2) delivery in these pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.
Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia
(Instituto Oswaldo Cruz, Ministério da Saúde, 1990) Roxana Carrasco; Hortensia Miguez; Clara Camacho; Lourdes Echalar; Suzana Revollo; Tania Ampuero; Jean-Pierre Dedet
Trypanosoma cruzi infection was studied in 1,298 sera samples of blood banks from 7 capital departments of Bolivia, using the immunofluorescence test (IFI) and Enzyme Linked Immunosorbent Assay (ELISA). The percentages of positivity in these 7 departments have an average of 28% and are distributed as follows: Sta. Cruz 51%, Tarija 45%, Cochabamba 28%, Sucre 39%, La Paz 4.9%, Oruro 6% and Potosi 24%. The prevalence is related with the altitude levels of the different departments. However in Potosi (3,945 m) we found a 24% of prevalence, probably due to the proximity of endemic valleys to the city. The authors suggest a strict control in blood donors since there exists a great risk of infection.
Salivary/Serum Progesterone Ratio Differs Between Menstrual Cycle Phases but Not Between Populations: Implications for Health, Reproductive, and Behavioral Research
(Wiley, 2025) Virginia J. Vitzthum; Diva Bellido; Lourdes Echalar; Esperanza Cáceres; Jonathan Thornburg
Hypothesis 1 was supported. Consistent with prior reports for other populations, in these Bolivian women UF was higher and more variable in the follicular than in the luteal phase. The source(s) of phase-associated variation in UF deserves additional study, particularly the dynamic relationship to different conformers of corticosteroid-binding globulin (CBG). Hypothesis 2 was not supported. Paired PFree-SAL and PTotal-VEN were highly correlated, and UF in these Bolivians was comparable to published values for other populations. Hypothesis 3 was not supported. There was no evidence that some individuals have consistently higher (or lower) UF than most other persons. In sum, these findings do not support the suggestions that the physiology underlying the relationship between PFree-SAL and PTotal-VEN differs substantially and inexplicitly between populations and individuals. These results also reinforce the critical roles of fastidious attention to sample collection and handling, judicious assessment of assay results, and appropriate statistical methods when using ovarian steroid data in any project. We suggest some guidelines for meeting these requirements. Used with due consideration for its advantages and limitations, PFree-SAL reliably tracks PTotal-VEN during the menstrual cycle and is a useful option in the biomarker toolkit. Just as it is costly to continue our work with tools not up to the task, so is it costly to discard useful tools without good reason. The development (and improvement through replication) of a robust toolkit for assessing changes in and the impacts of menstrual cycle hormones is foundational to reducing gender-based health disparities. (The linked file listed below under "Supporting Information" presents these findings in Spanish).
Where the O2goes to: preservation of human fetal oxygen delivery and consumption at high altitude
(Wiley, 2008) Lucrecia Postigo; Gladys Heredia; Nicholas P. Illsley; Tatiana Torricos; Caitlin Dolan; Lourdes Echalar; Wilma Téllez; Iván Maldonado; Michael Brimacombe; Elfride Balanza
Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O(2) delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O(2) delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude-associated decrease in birth weight was greater in Europeans (-417 g) than Andeans (-228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O(2) delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left-shifted at 3600 m. Fetuses receiving less O(2) extracted more (r(2) = 0.35, P < 0.0001). These adaptations resulted in similar fetal O(2) delivery and consumption across all four groups. Increased umbilical venous O(2) delivery correlated with increased fetal O(2) consumption per kg weight (r(2) = 0.50, P < 0.0001). Blood flow (r(2) = 0.16, P < 0.001) and O(2) delivery (r(2) = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r(2) = 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O(2) extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth.