Search

Trisomy 18 is usually a lethal chromosomal abnormality and is the second most common autosomal trisomy in humans, with an incidence of 1:8000 live births. It is commonly associated with abnormalities of the lower and upper extremities, having the frequency of 95% and 65%, respectively. A newborn female olive baboon (Papio hamadryas anubis) was diagnosed with intrauterine growth retardation and severe arthrogryposis-like congenital joint deformities. Cytogenetic analysis including G-banding and fluorescence in situ hybridization (FISH) revealed that the congenital abnormalities were associated with chromosomal mosaicism for trisomy 18. Genetic analysis with microsatellites from chromosome 18 confirmed the maternal origin of the extra chromosome 18. This is the first report of trisomy 18 in the baboon, which may be a promising animal model of human disease. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The abdominal pregnancy is a rare, but life threatening complication of ectopic embryo implantation. Only three cases of abdominal pregnancy have been previously described in primates: in a squirrel monkey, owl monkey and in a rhesus macaque. A 14-year-old wild-caught olive baboon ( Papio cynocephalus anubis) was diagnosed at the ultrasound examination with advanced gestational age extrauterine pregnancy. At the initial laparotomy and necropsy the diagnosis of abdominal pregnancy was made on Studdiford's criteria. This case indicates the possibility of developing a model for further study of different types of ectopic pregnancy and indicates a cesarean section as a risk factor for abdominal pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Placental dysfunction is an underlying cause of many major obstetric diseases and treatment options for complications like fetal growth restriction (FGR) are limited .We previously demonstrated nanoparticle delivery of the human insulin-like growth factor 1 (hIGF1) transgene under control of the trophoblast-specific PLAC1 promoter maintains normal fetal growth in a surgically-induced FGR mouse model. However, uptake by human placental syncytiotrophoblast has yet to be determined., Methods: An ex vivo human placenta perfusion model, term placenta villous fragments, and other in vitro syncytiotrophoblast models were used to determine nanoparticle uptake, transgene expression, and functional responses under oxidative stress conditions., Results: In the ex vivo perfusion, fluorescence from a Texas-Red conjugated nanoparticle increased in maternal perfusate upon nanoparticle addition and declined by the conclusion of the experiment (P < 0.001. Fluorescent histology confirmed localization in the syncytiotrophoblasts. No Texas-Red fluorescence was detected in the fetal perfusate. Transgene expression of hIGF1 in differentiated BeWo cells, isolated primary trophoblasts and fragments was increased compared to untreated (55,000-fold, P = 0.0003; 95-fold, P = 0.003; 400-fold, P < 0.001, respectively). Functionally, increased hIGF1 expression in villous fragments resulted in translocation of glucose transporter 1 to the syncytiotrophoblast cell membrane and under conditions of oxidative stress in BeWo cells, protected against increased cell death (P < 0.01) and decreased mitochondrial activity (P < 0.01)., Conclusion: The current study confirms that our nanoparticle is capable of uptake in human placental syncytium which results in enhanced transgene expression, functional changes to cellular activity and protection against increased oxidative stress., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Biofilm is a fundamental bacterial survival mode which proceeds through three main generalized phases: adhesion, maturation, and dispersion. Lactobacilli spp. (LB) are critical components of gut and reproductive health and are widely used probiotics. Evaluation of time-dependent mechanisms of biofilm formation is important for understanding of host-microbial interaction and development of therapeutic interventions. Time-dependent LB biofilm growth was studied in two systems: large biofilm output in continuous flow system (microfermenter (M), Institute Pasteur, France) and electrical impedance-based real time label-free cell analyzer (C) (xCELLigence, ACEA Bioscience Inc., San Diego, CA). L. plantarum biofilm growth in M system was video-recorded, followed by analyses using IMARIS software (Bitplane, Oxford Instrument Company, Concord, MA, USA). Additionally, whole genome expression and analyses of attached (A) and dispersed (D) biofilm phases at 24 and 48 h were performed., Results: The dynamic of biofilm growth of L. plantarum was similar in both systems except for D phases. Comparison of the transcriptome of A and D phases revealed, that 121 transcripts differ between two phases at 24 h. and 35 transcripts - at 48 h. of M growth. The main pathways, down-regulated in A compared to D phases after 24 h. were transcriptional regulation, purine nucleotide biosynthesis, and L-aspartate biosynthesis, and the upregulated pathways were fatty acid and phospholipid metabolism as well as ABC transporters and purine nucleotide biosynthesis. Four LB species differed in the duration and amplitude of attachment phases, while growth phases were similar., Conclusion: LB spp. biofilm growth and propagation area dynamic, time-dependent processes with species-specific and time specific characteristics. The dynamic of LB biofilm growth agrees with published pathophysiological data and points out that real time evaluation is an important tool in understanding growth of microbial communities.

Poor nutrition during pregnancy is a worldwide public health problem. Maternal nutrient reduction (MNR) is associated with maternal and fetal stress and a sex-dependent decrease in nonhuman primate (NHP) cognitive performance. Early life stress potentiates epileptogenesis in a sex-specific manner, and temporal lobe (TL) epilepsy is associated with neurocognitive disorders. The endogenous cannabinoid system (ECS) demonstrates remarkable developmental changes and plays a key role in aging-related diseases (e.g., dementia). Baboons have been studied as a natural model of epilepsy and express all ECS system components. We therefore evaluated baboon fetal temporal cortex ECS ontogenic and MNR-dependent changes. At 120 days gestational age (dGA) (term 185 days), maternal, fetal, and placental morphometry were similar between control and MNR pregnancies. MNR maternal weight gain was decreased compared with controls at 165 dGA independent of fetal sex. In male fetuses, expression of ECS synthesizing and degrading enzymes was gestational age-dependent, with the exception of fatty acid amide hydrolase (FAAH). MNR had a sex-specific effect on the protein expression of CB1R during development: CB1R protein expression was decreased in fetal temporal cortex of male fetuses at 120 and 140 dGA. Our data reveal that the MNR has sex-specific effects on temporal cortical expression of the ECS in baboon offspring and shows vulnerability of ECS in male fetuses during gestation., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Aims: Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity., Methods: Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated., Results: Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = - 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm 2 , p = 0.02)., Conclusions: Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition.

We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Gut microbial communities are critical players in the pathogenesis of obesity. Pregnancy is associated with increased bacterial load and changes in gut bacterial diversity. Sparse data exist regarding composition of gut microbial communities in obesity combined with pregnancy., Material and Methods: Banked tissues were collected under sterile conditions during necropsy, from three non-obese (nOb) and four obese (Ob) near-term pregnant baboons. Sequences were assigned taxonomy using the Ribosomal Database Project classifier. Microbiome abundance and its difference between distinct groups were assessed by a nonparametric test., Results: Three families predominated in both the nOb and Ob colonic microbiome: Prevotellaceae (25.98% and 32.71% respectively), Ruminococcaceae (12.96% and 7.48%), and Lachnospiraceae (8.78% and 11.74%). Seven families of the colon microbiome displayed differences between Ob and nOb groups., Conclusion: Changes in gut microbiome in pregnant obese animals open the venue for dietary manipulation in pregnancy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Imaging of placental tissues is a difficult task, because of specific for this organ complex multicellular and 3D tissue structure. The tissue clearing systems (X-CLARITY) system is a valuable tool for the examining the expression of molecular pathways in whole tissues and organs, originally developed for brain imaging.In the present report, we utilized this technology for the examination of placental vasculature and protein expression in perfused human placental tissue.The placental tissue was sufficiently cleared with preservation of endothelial staining and fluorescent markers, allowing visualization using confocal microscopy. The CLARITY method and X-CLARITY system is a valuable tool in placental imaging.

Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long- and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/an-hydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane - either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intra-amniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR)=0.66), neonatal infections (RR=0.67) and abnormal ultrasound scan of neonatal brain (RR=0.67)]. The positive effect of continuous amnioinfusion through the subcutaneously implanted perinatal port system with amniotic fluid like hypo-osmotic solution in "classic PPROM" less than 28/0 weeks' gestation shows promise but must be proved in future prospective randomized studies. Systemic antibiotics administration in "pre-PPROM" without infection and hospitalization are also of questionable benefit and needs to be further evaluated in well-designed randomized prospective studies to evaluate if it is associated with any neonatal benefit as well as the relationship to possible adverse effect of antibiotics on to fetal development and neurological outcome.

Disorders of sexual development are rare in non-human primates. We report a case of true hermaphroditism in a 19-year-old, nulliparous, female baboon (Papio spp.). At necropsy, the animal was obese with adequate muscle mass and hydration. Reproductive organs appeared normal with the exception of 2 firm nodular structures in the myometrium (1-1.5 cm diameter) and a thickened, dark endocervical mucosa. Histologically, both gonads were ovotestes and contained discrete areas of ovarian and testicular tissue. There were follicles in various stages of development surrounded by ovarian stroma. Other areas contained hypoplastic seminiferous tubules lined by Sertoli cells, but lacked germ cells and spermatozoa. The uterine lesions were consistent with adenomyosis and cystic endometrial hyperplasia. Cervical lesions were consistent with atypical glandular hyperplasia and squamous metaplasia with dysplasia. We report the first case of ovotesticular disorder of sexual development (OT-DSD), or true hermaphroditism in a baboon., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Maternal obesity in pregnancy has been linked to a spectrum of adverse developmental changes. Involvement of eCBs in obesity is well characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. This study evaluated fetomaternal hepatic, systemic, and placental eCB molecular changes in response to maternal consumption of a HFD. From ≥9 mo before conception, nonpregnant baboons ( Papio spp.) were fed a diet of either 45 (HFD; n = 11) or 12% fat or a control diet (CTR; n = 11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify AEA and 2-AG. Placental, maternal and fetal hepatic tissues were analyzed using RT-PCR, Western blot, and immunohistochemistry. mRNA and protein expression of endocannabinoid receptors (CB1R and CB2R), FAAH, DAGL, MAGL, and COX-2 were determined. Statistical analyses were performed with the nonparametric Scheirer-Ray-Hare extension of the Kruskal-Wallis test to analyze the effects of diet (HFD vs. CTR), fetal sex (male vs. female), and the diet × sex interaction. Fetal weight was influenced by fetal sex but not by maternal diet. The increase in maternal weight in animals fed the HFD vs. the CTR diet approached significance ( P = 0.055). Maternal circulating 2-AG concentrations increased, and fetal circulating concentrations decreased in the HFD group, independently of fetal sex. CB1R receptor expression was detected in syncytiotrophoblasts (HFD) and the fetal endothelium (CTR and HFD). Placental CB2R protein expression was higher in males and lower in female fetuses in the HFD group. Fetal hepatic CB2R, FAAH, COX-2 (for both fetal sexes), and DAGLα (in male fetuses) protein expression decreased in the HFD group compared with the CTR group. We conclude that consumption of a HFD during pregnancy results in fetal systemic 2-AG and hepatic eCB deficiency.

Background: The condition termed cannabinoid hyperemesis syndrome (CHS) was characterized a decade ago by Allen et al. and includes cyclic episodes of nausea and vomiting and the learned behavior of hot bathing in individuals with chronic cannabis abuse. During pregnancy, the differential diagnosis of this syndrome is challenging, since it can be masked by typical symptoms of early pregnancy or by hyperemesis gravidarum, a complication of early pregnancy associated with excessive nausea and vomiting., Case Description: The authors herein describe the case of a 21-year-old primigravida patient diagnosed with hyperemesis gravidarum at 6 weeks of gestation and with preeclampsia at 35 weeks. At 30 weeks of gestation, a drug screen was performed that was positive for cannabis; therefore, a diagnosis of CHS was made. After labor induction, the patient delivered an infant who developed normally and had a negative drug test of the umbilical cord blood. Esophagogastroduodenoscopy was performed 9 days post delivery, with biopsies taken of the duodenal, gastric, and esophageal tissues. Moderate chronic gastritis with lymphoid aggregates and slight acute inflammation were noticed, whereas no malignancy, dysplasia, or goblet cell metaplasia was detected. A number of Helicobacter-like organisms were identified by H. pylori immunostaining., Conclusion: Presented here is the first case reporting an association of chronic cannabis use with H. pylori colonization and preeclampsia in pregnancy, which brings to light the possible involvement of a cannabinoid-related pathway in the link between pregnancy-specific complications and bacterial colonization.

The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a "developmental programming" phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome. Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004. Cannabinoids have been used for the treatment of chronic pain for millenniums and act through the mechanism of "kick-starting" the components of the endogenous cannabinoid system (ECS). ECS is a pharmacological target for the treatment of obesity, inflammation, cardiovascular and neuronal damage, and pain. We hypothesize that the deteriorating effect of maternal obesity on offspring health is explained by the mechanism of Fetal Syndrome of Endocannabinoid Deficiency (FSECD), which accompanies maternal obesity. Here we provide support for this hypothesis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Evolutionary approaches are powerful tools for understanding human disorders. The composition of vaginal microbiome is important for reproductive success and has not yet been characterized in the contexts of social structure and vaginal pathology in non-human primates (NHPs). We investigated vaginal size, vulvovaginal pathology and the presence of the main human subtypes of Lactobacillus spp./ BV-related species in the vaginal microflora of baboons (Papio spp.). We performed morphometric measurements of external and internal genitalia (group I, n = 47), analyzed pathology records of animals from 1999-2015 (group II, n = 64 from a total of 12,776), and evaluated vaginal swabs using polymerase chain reaction (PCR) (group III, n = 14). A total of 68 lesions were identified in 64 baboons. Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, Megasphaera I, and Megasphaera II were not detected. L. jensenii, L. crispatus, and L. gasseri were detected in 2/14 (14.2%), 1/14 (7.1%), and 1/14 (7.1%) samples, respectively. BVAB2 was detected in 5/14 (35.7%) samples. The differences in the vaginal milieu between NHP and humans might be the factor associated with human-specific pattern of placental development and should be taken in consideration in NHP models of human pharmacology and microbiology.

Introduction: To assess the effects of selective reduced uterine perfusion pressure (SRUPP) in pregnant rats., Methods: 20 pregnant Sprague-Dawley rats were allocated either to an intervention group, exposed to SRUPP (n = 10) or a control group, exposed to sham surgery (n = 10). Such procedures were performed on gestational day (GD) 14. The Mean arterial pressure (MAP) was measured on GD14 (before surgery) and GD20. We measured 18 h proteinuria on GD20. On GD21, mean fetal (MFW) and placental (MPW) weights were obtained. Oxidative stress and angiogenic markers were measured in placental tissue and urine. Mann Whitney U or Independent samples T test were used when appropriate. A two-sided P < 0.05 indicated statistical significance., Results: MAP on GD20 was higher in the intervention group (109 ± 1.7 mmHg) when compared with the control group (83 ± 1.5 mmHg) (P = 0.002). There was no significant difference in urinary protein excretion (117 ± 3.1 mg/24 h versus 136 mg ± 2.8/24 h, P = 0.18), MFW (4.14 ± 0.05 versus 4.39 ± 0.04 g, P = 0.19) or MPW (0.43 ± 0.008 versus 0.44 ± 0.006 g, P = 0.73) between the intervention and the control groups, respectively. The oxidative stress was increased; whereas, the sFLT1 expression was not increased when the SRUPP group was compared with controls., Discussion: SRUPP is associated with an increase in maternal MAP and oxidative stress and therefore it may become a useful tool in the study of pregnancy-related hypertensive disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications., Material and Methods: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed., Results: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group., Discussion: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied., (© 2014 S. Karger AG, Basel.)

Many of melatonin's actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: More than one-fourth of U.S. women are overweight; more than one-third are obese. Maternal obesity has been linked to an increased incidence of stillbirths, fetal macrosomia, fetal intrauterine growth restriction and pre-eclampsia. The placenta plays a key role in the nutrients and oxygen supply to the fetus. The data about structural changes in the placental villous membrane (VM), a major component of the feto-maternal nutrient and oxygen exchange barrier, during obesity are sparse and inconsistent. Our objective was to evaluate the morphometric changes in the placental exchange barrier in a baboon model of obesity., Materials and Methods: The previously described baboon model of maternal obesity was studied. We compared 4 obese to 4 non-obese baboons. Placental stereology with the use of transmission electron microscopy was performed to estimate VM oxygen diffusing capacities and morphometry., Results: The specific placental oxygen diffusing capacities per unit of fetal weight were similar in baboons and humans. Maternal leptin concentrations correlated negatively with placental basement membrane thickness (r = -0.78, p < 0.05), while fetal leptin levels correlated negatively with endothelial thickness of fetal capillaries (r = -0.78, p < 0.05). The total and specific villous membrane oxygen diffusing capacities were not different between the two groups., Conclusion: To the best of our knowledge this is the first report of placental oxygen diffusing capacities and placental ultrastructural changes in a baboon model of obesity. Previously reported placental inflammation in maternal obesity is not associated with changes in the VM diffusing capacities and ultrastructure., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Our objective was to determine signaling molecules and apoptosis rate in the term placenta of a baboon model of maternal nutrient reduction (MNR)., Study Design: Female baboons were fed ad libitum for controls (n = 7) or 70% of control baboon diet (MNR; n = 6) from 30-165 days of gestation with necropsy at 165 days of gestation. Placental tissues were collected and fixed for immunohistochemistry or snap frozen to measure extracellular signal-regulated kinases, protein kinase B, JUN NH(2)-terminal kinase, X-linked inhibitor of apoptosis protein, and caspase 3. Placental villous apoptosis was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling and cytokeratin 18 cleavage., Results: Compared with the control placentas, MNR placentas demonstrated reduced placental weight (P < .02), decreased phospho (p)-ERK (P < .04), increased placental villous apoptosis (P < .001), increased villous cytokeratin 18 cleavage, increased X-linked inhibitor of apoptosis protein (P < .007), and increased active caspase 3 (P < .02)., Conclusion: We conclude that placental apoptosis is increased in this baboon model of MNR at term and that the increase in X-linked inhibitor of apoptosis protein may be a protective mechanism against this apoptosis., (Published by Mosby, Inc.)

A highly sensitive and specific LC-MS/MS assay was developed and validated to quantify nevirapine (NVP) and its five metabolites [2-, 3-, 8-, 12-hydroxyl NVP (OHNVP) and 4-carboxyl NVP (CANVP)] simultaneously in baboon serum and the assay was used to characterize their pharmacokinetic studies of an oral-dose escalation study in baboon. The lower limit of quantification (LLOQ) for NVP and its four hydroxyl nevirapine metabolites was 1.0 ng/mL and for 4-CANVP was 5.0 ng/mL. The between-run and within-run precisions and accuracies at four quality control concentrations (1, 5, 50 and 500 ng/mL) were evaluated in baboon serum with less than 14% variation and 93-114% accuracies (n = 6), except for the LLOQ for 2-OHNVP, which had an accuracy of 115.8% for between-run validation. The pharmacokinetics of NVP and its five metabolites in non-pregnant baboons by a single-dose escalation study were also profiled. The major metabolites detected were 4-CANVP and 12-OHNVP. 3-OHNVP and 2-OHNVP were the minor metabolites with only a trace amount of 2-OHNVP detected in some pharmacokinetic samples. No 8-OHNVP was observed in all of the pharmacokinetic samples. In addition, the fragmentation for the four hydroxyl metabolite isomers is also discussed., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Maternal obesity is present in 20-34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes in the placenta. The major findings of this study were: 1) decreased placental syncytiotrophoblast amplification factor, intact syncytiotrophoblast endoplasmic reticulum structure and decreased system A placental amino acid transport in obese animals; 2) fetal serum amino acid composition and mononuclear cells (PBMC) transcriptome were different in fetuses from obese compared with non-obese animals; and 3) maternal obesity in humans and baboons is similar in regard to increased placental and adipose tissue macrophage infiltration, increased CD14 expression in maternal PBMC and maternal hyperleptinemia. In summary, these data demonstrate that in obese baboons in the absence of increased fetal weight, placental and fetal phenotype are consistent with those described for large-for-gestational age human fetuses.

Information on the influence of poor maternal nutrition on the regulation of responses to pregnancy, placental and fetal growth and development is critical to a better understanding of pregnancy physiology and pathophysiology. We determined normal changes and effects of controlled and monitored moderate nutrient restriction (NR) (global nutrient intake reduced to 70% of food consumed by mothers feeding ad libitum from 0.16 to 0.5 of gestation) in the baboon, on important hematological, biochemical, and hormonal indices of fetal growth and placental function. Serum IGF-I:IGFBP-3 ratio was lower in pregnant than control non-pregnant baboons feeding ad libitum. Serum concentrations of total and free IGF-I were decreased in NR mothers compared with controls (p<0.05). The decrease in fetal IGF-I did not reach significance (p=0.057). Serum IGF-I: IGFBP-3 ratio was decreased by NR in both mothers and fetuses. Maternal serum IGF-II was unchanged by NR. Placental IGF-I mRNA and protein abundance were similarly reduced whereas IGF-II mRNA increased in placental tissue of NR compared to control mothers. Systemic (maternal) and local (placental) IGFBP-1 and IGFBP-3 mRNA and protein abundance were unchanged by NR. Type 1 IGF receptor protein in the syncytiotrophoblast increased in NR. Type 2 IGF receptor protein was present in the stem villi core, and decreased after NR. We conclude that moderate NR in this important non-human primate model significantly disrupts the maternal and placental IGF-IGFBP axis and influences placental expression of this key system at the gene and protein level. Changes observed appear to be directed toward preserving placental growth.

Interpretation of gene array data presents many potential pitfalls in adult tissues. Gene array techniques applied to fetal tissues present additional confounding pitfalls. The left lobe of the fetal liver is supplied with blood containing more oxygen than the right lobe. Since synthetic activity and cell function are oxygen dependent, we hypothesized major differences in mRNA expression between the fetal right and left liver lobes. Our aim was to demonstrate the need to evaluate RNA samples from both lobes. We performed whole genome expression profiling on left and right liver lobe RNA from six 90-day gestation baboon fetuses (term 180 days). Comparing right with left, we found 875 differentially expressed genes - 312 genes were up-regulated and 563 down-regulated. Pathways for damaged DNA binding, endonuclease activity, interleukin binding and receptor activity were up-regulated in right lobe; ontological pathways related to cell signalling, cell organization, cell biogenesis, development, intracellular transport, phospholipid metabolism, protein biosynthesis, protein localization, protein metabolism, translational regulation and vesicle mediated transport were down-regulated in right lobe. Molecular pathway analysis showed down-regulation of pathways related to heat shock protein binding, ion channel and transporter activities, oxygen binding and transporter activities, translation initiation and translation regulator activities. Genes involved in amino acid biosynthesis, lipid biosynthesis and oxygen transport were also differentially expressed. This is the first demonstration of RNA differences between the two lobes of the fetal liver. The data support the argument that a complete interpretation of gene expression in the developing liver requires data from both lobes.

Baboons are very similar to humans in ontogeny, reproductive physiology, and placentation, and thus serve as an excellent nonhuman primate model for use in both normative and perturbation studies of pregnancy that cannot be performed on pregnant women. However, little is known about the changes induced by normal pregnancy in the maternal and fetal baboon in lymphocyte subset composition, and lymphocyte activation and proliferation. We performed multicolor flow cytometry analysis of peripheral venous blood samples obtained from pregnant baboons at mid-gestation (0.5 G), and from matched fetal heart (FH) and umbilical cord (UC) blood at the end of gestation (0.95 G). Compared with their mothers at 0.95 G, fetal lymphocytes had higher percentages of B and CD4+ T cells, and lower numbers of NK and CD8+ T cells. When comparing pregnant baboons at 0.5 and 0.95 G, we also found that pregnancy induces immune stimulation, measured as higher activation without proliferation of CD8+ T and NK cells in the maternal circulation. Our study adds new data to support the notion of pregnancy-induced immune activation and strengthens the value of the baboon as a nonhuman primate model for studies pertinent to human reproductive physiology, pathology, and vaccination.