Prenatal Exposure to Maternal Depressed Mood and the MTHFR C677T Variant Affect SLC6A4 Methylation in Infants at Birth

Background

Prenatal and early postnatal exposure to maternal depression may “program” childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.

Methods/Principal Findings

Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2^nd and 3^rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2^nd trimester depressed mood (p<0.05). Increased 2^nd trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.

Conclusions

These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.     

Ontogenic Development of Corticotrophs in Fetal Buffalo (Bubalus Bubalis) Pituitary Gland

To evaluate the subpopulation of corticotrophs in developing buffalo (Bubalus bubalis) fetus, pituitary glands were recovered (n=6 per group) from late first, second and third gestational female buffalo dams. The corticotrophs were identified by using specific antibodies against proopiomelanocortin (POMC) and adrenocorticotrophic hormone (ACTH) through immunohistochemistry. There was a significant (P≤0.05) increase of immunoreactive (ir) ir-ACTH cells during late 2^nd trimester while, ir-POMC cells were more (P≤0.05) at late 3^rd trimester of gestation as compared to other age groups. The quantity of co-localized cells for POMC and ACTH was significantly (P≤0.05) greater at the end of 1^st gestation rather than 2^nd and 3^rd gestational fetal adenohypophyseal cells. This study is the first to demonstrate co-localization of POMC+ACTH and the affect of gestational age on the expression of these cells in buffalo fetus adenohypophysis.Key words: buffalo, corticotrophs, fetus, pituitary gland, immunohistochemistry     

Heritability estimates of body size in fetal life and early childhood

Background

The objective was to estimate the heritability for height and weight during fetal life and early childhood in two independent studies, one including parent and singleton offsprings and one of mono- and dizygotic twins.

Methods

This study was embedded in the Generation R Study (n = 3407, singletons) and the Netherlands Twin Register (n = 33694, twins). For the heritability estimates in Generation R, regression models as proposed by Galton were used. In the Twin Register we used genetic structural equation modelling. Parental height and weight were measured and fetal growth characteristics (femur length and estimated fetal weight) were measured by ultrasounds in 2^nd and 3^rd trimester (Generation R only). Height and weight were assessed at multiple time-points from birth to 36 months in both studies.

Results

Heritability estimates for length increased from 2^nd to 3^rd trimester from 13% to 28%. At birth, heritability estimates for length in singletons and twins were both 26% and 27%, respectively, and at 36 months, the estimates for height were 63% and 72%, respectively. Heritability estimates for fetal weight increased from 2^nd to 3^rd trimester from 17% to 27%. For birth weight, heritability estimates were 26% in singletons and 29% in twins. At 36 months, the estimate for twins was 71% and higher than for singletons (42%).

Conclusions

Heritability estimates for height and weight increase from second trimester to infancy. This increase in heritability is observed in singletons and twins. Longer follow-up studies are needed to examine how the heritability develops in later childhood and puberty.     

Lower Inter-Partum Interval and Unhealthy Life-Style Factors Are Inversely Associated with n-3 Essential Fatty Acids Changes during Pregnancy: A Prospective Cohort with Brazilian Women

Objective

To analyze serum fatty acids concentrations during healthy pregnancy and evaluate whether socioeconomic, demographic, obstetric, nutritional, anthropometric and lifestyle factors are associated with their longitudinal changes.

Study design

A prospective cohort of 225 pregnant women was followed in the 5^th–13^th, 20^th–26^th and 30^th–36^th weeks of gestation. Serum samples were collected in each trimester of pregnancy and analyzed to determine the fatty acids composition using a high-throughput robotic direct methylation method coupled with fast gas-liquid chromatography. The independent variables comprised the subjects’ socioeconomic and demographic status, obstetric history, early pregnancy body mass index (BMI), dietary and lifestyle parameters. Analyses were performed using linear mixed-effects models.

Results

The overall absolute concentrations of fatty acids increased from the 1^st to the 2^nd trimester and slightly increased from the 2^nd to the 3^rd trimester. Early pregnancy BMI, inter-partum interval and weekly fish intake were the factors associated with changes in eicosapentaenoic + docosahexaenoic acids (EPA+DHA) and total n-3 polyunsaturated fatty acids (PUFAs). Early pregnancy BMI, age and monthly per-capita income were inversely associated with the changes in the n-6/n-3 ratio. Alcohol consumption was positively associated with the n-6/n-3 ratio.

Conclusion

Early pregnancy BMI was positively associated with EPA+DHA and total n-3 PUFAs, while presenting a reduced weekly fish intake and a lower inter-partum interval were associated with lower levels of n-3 PUFAs. A lower per-capita family income and a drinking habit were factors that were positively associated with a higher n-6/n-3 ratio.     

Homing Receptor Expression Is Deviated on CD56+ Blood Lymphocytes during Pregnancy in Type 1 Diabetic Women

Type 1 Diabetes Mellitus (T1DM) is characterized by an augmented pro-inflammatory immune state. This contributes to the increased risk for gestational complications observed in T1DM mothers. In normal pregnancies, critical immunological changes occur, including the massive recruitment of lymphocytes, particularly CD56^bright NK cells, into early decidua basalis and a 2^nd trimester shift towards Type 2 immunity. Decidual CD56^bright NK cells arise at least partly from circulating progenitors expressing adhesion molecules SELL and ITGA4 and the chemokine receptors CXCR3 and CXCR4. In vitro studies show that T1DM reduces interactions between blood CD56⁺ NK cells and decidual endothelial cells by reducing SELL and ITGA4-based interactions. To address the mechanisms by which specific lymphocyte subsets may be recruited from the circulation during pregnancy and whether these mechanisms are altered in T1DM, flow cytometry was used to examine eight peripheral blood lymphocyte subsets (Type 1 (IL18R1⁺) and Type 2 (IL1RL1⁺) CD56^bright NK, CD56^dim NK, NKT and T cells) from control and T1DM women. Blood was collected serially over pregnancy and postpartum, and lymphocytes were compared for expression of homing receptors SELL, ITGA4, CXCR3, and CXCR4. The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM. CD56^bright NK cells from control women had the highest expression of all four receptors with greatest expression in 2^nd trimester. At this time, these receptors were expressed at very low levels by CD56^bright NK cells from TIDM patients. Type 1/Type 2 NKT cell ratios were not influenced by either pregnancy or TIDM. Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56^bright NK cells. This implicates CD56^bright NK cells in diabetic pregnancy complications.     

Effect of Water Stress on Photosynthesis and Growth in Two Teak Phenotypes

Two teak (Tectona grandis L.f.) phenotypes differing in their leaf length/breadth ratios were subjected to water stress by withholding water supply for three weeks. Growth rates of whole plants, developing leaves (1^st and 2^nd from shoot apices), and 2^nd and 3^rd internodes were higher in broad leaved (BL) phenotype than in narrow leaved (NL) phenotype before and after imposing water stress treatment. However, the effect of water stress on these parameters was higher in the BL phenotype than in the NL one. Diurnal course of net photosynthetic rate (P _N) of 3^rd or 4^th leaves from shoot apices measured under well-watered conditions was higher for the NL than BL phenotype. P _N, stomatal conductance (g _s), and transpiration rate (E) in both phenotypes were negatively affected by water stress and their decline under water stress was significantly higher in the BL than NL plants.     

Endothelium-derived nitric oxide synthase protein expression in ovine placental arteries

During the third trimester, fetoplacental and uterine blood flows increase dramatically to meet the high metabolic demands of the growing fetus. We hypothesized that the expression of endothelial nitric oxide synthase (eNOS) in fetoplacental artery endothelium and the concentrations of nitric oxide (NO) and cyclic GMP (cGMP) in amniotic fluid (AF) are increased during the third trimester of ovine gestation. Placental arteries and AF were collected from ewes at 110, 120, 130, and 142 days of gestation (n = 24; mean +/- SEM term = 145 +/- 3 days). Expression of eNOS protein was measured in intact and denuded placental arteries and in endothelium-derived protein by Western analysis and confirmed by immunohistochemistry. Concentrations of NO (nitrates plus nitrites) and cGMP were determined in AF. Placental artery eNOS protein expression was localized to the endothelium, where it was markedly greater than in vascular smooth muscle. Placental artery endothelium-derived eNOS expression and AF cGMP concentrations were similar at 110 and 120 days of gestation; however, both peaked at 130 days at levels two- to threefold above baseline (P < 0.05) before returning to baseline at 142 days of pregnancy. The AF NO (nitrates plus nitrites) levels, however, increased progressively between 120 days of gestation and term (P < 0.05). We concluded that endothelium-derived placental artery eNOS levels, AF NO (nitrates plus nitrites), and AF cGMP were markedly increased during the third trimester, thus supporting a role for NO-mediated elevations in cGMP in the control of fetoplacental blood flow.     

Factors influencing the priority of access to food and their effects on the carcass traits for Japanese Black (Wagyu) cattle

The factors influencing the priority of access to food and the effects of the priority of access to food on their carcass traits were analyzed for Japanese Black (Wagyu) cattle in a semi-intensive fattening production system. The records of 96 clinically healthy steers and heifers were analyzed. The calves at ∼3 to 4 months of age were allocated to pens with four animals per pen; all four animals in the same pen were of the same sex and of similar body size. The ranking of the animals’ priority of access to food (1^st, 2^nd, 3^rd and 4^th), which was determined by the farm manager, was used as an indicator of social dominance in the present study. Four models including sire line, maternal grandsire line and the difference in the animals’ birth dates as fixed effects were used to analyze factors influencing the priority of access to food. Ranking was represented by ordinal scores (highest=4, lowest=1) in Model 1, and the binary scores were assigned in Model 2 (highest=1; 2^nd, 3^rd and 4^th=0), Model 3 (1^st and 2^nd=1; 3^rd and 4^th=0) and Model 4 (1^st, 2^nd and 3^rd=1; lowest=0). The results showed that the difference in the animals’ birth dates had a significant effect on the establishment of the priority of access to food in Model 3 (P<0.05), suggesting that animals born earlier may become more dominant in the pen. The maternal grandsire line tended to affect the social rank score in Models 2 and 3 (P<0.10). Our results indicated that the maternal grandsire line may affect the temperament of calves through their mothers’ genetic performance and thereby more aggressive calves may be more dominant and have higher priority of access to food. On the other hand, there was a significant effect of the priority of access to food on beef marbling score (BMS; P<0.05), and the priority of access to food also tended to influence the carcass weight (P=0.09). The highest BMS was observed for animals with the first rank of the priority of access to food (P<0.05), and the higher-ranking animals had the tendency to be heavier carcass than the lower-ranking animals. Our findings emphasized the importance of information about the priority of access to food determined by farmers’ own observation on implementing best management practices in small-scaled semi-intensive beef cattle production systems.     

Association of Second and Third Trimester Weight Gain in Pregnancy with Maternal and Fetal Outcomes

Objective

To investigate the association between weekly weight gain, during the second and third trimesters, classified according to the 2009 Institute of Medicine (IOM/NRC) recommendations, and maternal and fetal outcomes.

Methods

Gestational weight gain was evaluated in 2,244 pregnant women of the Brazilian Study of Gestational Diabetes (Estudo Brasileiro do Diabetes Gestacional – EBDG). Outcomes were cesarean delivery, preterm birth and small or large for gestational age birth (SGA, LGA). Associations between inadequate weight gain and outcomes were estimated using robust Poisson regression adjusting for pre-pregnancy body mass index, trimester-specific weight gain, age, height, skin color, parity, education, smoking, alcohol consumption, gestational diabetes and hypertensive disorders in pregnancy.

Results

In fully adjusted models, in the second trimester, insufficient weight gain was associated with SGA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.26–2.33), and excessive weight gain with LGA (RR 1.64, 95% CI 1.16–2.31); in third trimester, excessive weight gain with preterm birth (RR 1.70, 95% CI 1.08–2.70) and cesarean delivery (RR 1.21, 95% CI 1.03–1.44). Women with less than recommended gestational weight gain in the 2^nd trimester had a lesser risk of cesarean deliveries (RR 0.82, 95% CI 0.71–0.96) than women with adequate gestational weight gain in this trimester.

Conclusion

Though insufficient weight gain in the 3^rd trimester was not associated with adverse outcomes, other deviations from recommended weight gain during second and third trimester were associated with adverse pregnancy outcomes. These findings support, in part, the 2009 IOM/NRC recommendations for nutritional monitoring during pregnancy.     

Immunogenicity of Seven-Valent Pneumococcal Conjugate Vaccine Administered at 6, 14 and 40 Weeks of Age in South African Infants

Background

The high cost of pneumococcal conjugate vaccine (PCV) and local epidemiological factors contributed to evaluating different PCV dosing-schedules. This study evaluated the immunogenicity of seven-valent PCV (PCV7) administered at 6-weeks; 14-weeks and 9-months of age.

Methods

250 healthy, HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines. Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1^st and 2^nd PCV-doses, prior to and two-weeks following the 3^rd dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes following the 2^nd and 3^rd PCV7-doses. Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14 weeks of age.

Results

The proportion of infants with serotype-specific antibody ≥0.35 µg/ml following the 2^nd PCV7-dose ranged from 84% for 6B to ≥89% for other serotypes. Robust antibody responses were observed following the 3^rd dose. The proportion of children with OPA ≥8 for serotypes 9V, 19F and 23F increased significantly following the 3^rd PCV7-dose to 93.6%; 86.0% and 89.7% respectively. The quantitative antibody concentrations following the 2^nd PCV7-dose were comparable to that after the 3^rd -dose in the 6-10-14 week schedule. Geometric mean concentrations (GMCs) following the 3^rd PCV7-dose were higher for all serotypes in this study compared to the historical cohort.

Conclusions

The studied PCV7 dosing schedule induced good immune responses, including higher GMCs following the 3^rd-dose at 9-months compared to when given at 14-weeks of age. This may confer longer persistence of antibodies and duration of protection against pneumococcal disease.     

Phenology ofHippodamia undecimnotata (Col.: Coccinellidae) in Greece

Hippodamia (Semiadalia) undecimnotata (Coleoptera: Coccinellidae), collected from central Greece and reared in cages during 1993–1994 and in vials during 1994–1995 outdoors at Kifissia, Athens, completed 5 generations per year. In both cases, adults of the 1^st, 2^nd and 3^rd generations reproduced, completing their egg laying in the same year; 4^th and 5^th generation adults reproduced both in the year they emerged and the following year. In both cases, adults of the 1^st and 2^nd generations died before winter; in 1993, adults of the 3^rd generation died before winter, in 1994, they survived until April 1995. Adults of the 4^th and 5^th generations overwintered successfully. The greatest numbers of eggs were laid by females of the 1^st and 2^nd generations. Field observations and timed counts of specimens (30 minutes per location) made on the tops of Mounts Chlomo and Kitheron and on the neighboring plain of Kopais between 1991 and 1994 revealed that most adults arrived on the mountains between late June and early September and left between the end of March and beginning of May.H. undecimnotata were not found on the plain of Kopais during the winter. Overwintered adults arrived between the end of March and beginning of May; 1^st generation adults emerged in June. The presence of a few eggs, larvae, pupae and newly-emerged adults observed on the plain during August-September 1993 suggests that at least a portion of theH. undecimnotata population in central Greece completes 2 or more overlapping generations per year.     

Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China

Objective

To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes.

Methods

Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1^st and 3^rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes.

Results

Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09–2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17–3.27, and RR 2.33, 95%CI 1.22–4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09–1.73) and having macrosomia (RR 1.54, 95%CI 1.05–2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31–2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes.

Conclusions

Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results.     

Phenology ofCoccinella septempunctata (Col.: Coccinellidae) in central Greece

Coccinella septempunctata (Coleoptera: Coccinellidae), field collected from central Greece and reared in cages during 1990–1991 and in vials during 1994–1995 outdoors at Kifissia, Athens, developed 4 complete and a 5^th partial generations per year. In both cases, only adults of the 1st generation reproduced within the year they emerged; 2^nd, 3^rd and 4^th generation adults reproduced partly in the year they emerged and partly in the following year; 5^th generation adults did not reproduce at all in 1990, and eggs/larvae produced by 4^th generation females in 1994 died before developing into adults. Adults of the 1 st and 5th generations died before winter; those of the 2^nd, 3^rd and 4^th generations overwintered successfully. The greatest numbers of eggs were laid by females of the 1^st and 2^nd generations. Visual counts made in the open field at Kopais plain in central Greece (1990–1992) and on the summit of the adjacent Mount Kitheron (1990–1994) indicate that allC. septempunctata instars were abundant in the plain between April and June, becoming scarce from July until the end of the warm period of the year following spring. NoC. septempunctata individuals were found in the plain in winter. On the summit of the mountain,C. septempunctata adults were present all year round, singly and in aggregations, except for the month of May. The most numerous arrivals of adults were noticed on the mountain in June. Emigrations of adults from there were noticed from March until the end of April.     

Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy

The sugar moiety of IgA is known to provide a link between the innate and adaptive immune systems. Terminally located glycotopes on IgA are potential ligands engaged in the interactions which may modulate the biological activities of IgA. In the present work the expressions of Maackia amurensis (MAA), Sambucus nigra (SNA), Lens culinaris (LCA), Tetragonolobus purpureus (LTA), and Ulex europaeus (UEA) reactive glycotopes on maternal plasma and amniotic IgA were evaluated in relation to the progression of a normal human pregnancy, from the 2nd trimester, throughout the 3rd trimester, perinatal period, post-date pregnancy and delivery, by lectin-IgA-ELISA, using specific biotinylated lectins. The amniotic and maternal plasma IgA concentrations and a degree of SNA and LCA reactivity of maternal plasma IgA were almost unaltered during the normal pregnancy. The amniotic IgA from the 2nd trimester was decorated by MAA-, SNA-reactive and LCA-, LTA-, and UEA-reactive glycotopes. At the turn of the 2nd and 3rd trimesters the expression of MAA-, SNA-, LTA-, and UEA-reactive glycotopes, except for LCA-reactive, increased and remained almost at unaltered levels throughout the perinatal period and delivery. However, in the post-date pregnancy the expression of LCA-, LTA-, and UEA-reactive and SNA-reactive glycotopes were significantly higher. The unique fucosylated and sialylated glycovariants of amniotic IgA associated with the progression of the normal pregnancy may illustrate a general importance of carbohydrate-lectin receptor interactions in the control and modulation of biological events to ensuring homeostasis during pregnancy, protection and well-being of fetus.     

Amniotic Fluid Enhances Allogeneic Cytotoxic T Cell Responses,Whereas It Suppresses Mitogen-Stimulated Lymphocyte Proliferation

Mouse amniotic fluid has been shown to suppress T lymphocyte proliferation and suggested to be important in regulating immunity during pregnancy. In allogeneic pregnancy, cytotoxic T cells in pregnant lymphocytes against paternal transplantation antigen are impaired. We examined the effect of amniotic fluid to the alloreactive CTL responses. Although the amniotic fluid suppressed Con A or LPS stimulated lymphocyte proliferation as previously reported, the amniotic fluid taken from syngeneic C57BL/6 pregnant mice or allogeneic C57BL/6 × BALB/c pregnant mice enhanced the anti-H-2^d or anti-H-2^k CTL responses dose-dependently. We speculate that amniotic fluid contains not only immunosuppressive factors but also immunoenhancing factors which upregulate the allogeneic CTL responses.     

Dating of Pregnancy in First versus Second Trimester in Relation to Post-Term Birth Rate: A Cohort Study

Objectives

To evaluate in a national standardised setting whether the performance of ultrasound dating during the first rather than the second trimester of pregnancy had consequences regarding the definition of pre- and post-term birth rates.

Methods

A cohort study of 8,551 singleton pregnancies with spontaneous delivery was performed from 2006 to 2012 at Copenhagen University Hospital, Holbæk, Denmark. We determined the duration of pregnancy calculated by last menstrual period, crown rump length (CRL), biparietal diameter (1^st trimester), BPD (2^nd trimester), and head circumference and compared mean and median durations, the mean differences, the systematic discrepancies, and the percentages of pre-term and post-term pregnancies in relation to each method. The primary outcomes were post-term and pre-term birth rates defined by different dating methods.

Results

The change from use of second to first trimester measurements for dating was associated with a significant increase in the rate of post-term deliveries from 2.1–2.9% and a significant decrease in the rate of pre-term deliveries from 5.4–4.6% caused by systematic discrepancies. Thereby 25.1% would pass 41 weeks when GA is defined by CRL and 17.3% when BPD (2^nd trimester) is used. Calibration for these discrepancies resulted in a lower post-term birth rate, from 3.1–1.4%, when first compared to second trimester dating was used.

Conclusions

Systematic discrepancies were identified when biometric formulas were used to determine duration of pregnancy. This should be corrected in clinical practice to avoid an overestimation of post-term birth and unnecessary inductions when first trimester formulas are used.     

Human AB serum for generation of mesenchymal stem cells from human chorionic villi: comparison with other source and other media including platelet lysate

Objectives: We have investigated foetal mesenchymal stem cells (MSCs) obtained from first‐trimester chorionic villi (CV) and second‐trimester amniotic fluid (AF), comparing them to adult bone marrow‐derived MSCs. Materials and methods: We report on cell population growth in human allogeneic serum (HS) and platelet lysate (PL), immunophenotype, cytokine expression profile and immunoregulatory activity, of these foetal MSCs on stimulated peripheral blood mononuclear and lymphocyte subpopulations. Results: Chorionic villi cells grow rapidly in HS, with 20 populations doublings (PDs) after 59 days (six passages), and also in animal serum, with 27 PDs after 65 days (seven passages). PL allowed for expansion in 60% of the samples tested, although it was lower than in HS. HS supported an average of 40 PDs of expansion in 20% of AF cells after 90 days, whereas animal serum supported 28.5 PDs in 66 days. CV and AF cells inhibited proliferation of stimulated T lymphocytes, suppressing population growth of both CD4+ and CD8+ T subpopulations and sometimes also, CD19+ cells. Conclusions: Our results indicate that CV would be an optimal source of MSCs with high expansion potential in a HS propagation system and immunoregulatory capacity of T and B lymphocytes. More than 90% of CV samples achieved large‐scale expansion in HS, which is encouraging for potential clinical applications of these cells.     

Enhanced Deficits in Long-Term Potentiation in the Adult Dentate Gyrus with 2nd Trimester Ethanol Consumption

Ethanol exposure during pregnancy can cause structural and functional changes in the brain that can impair cognitive capacity. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. In the present experiments we sought to determine if the functional effects of developmental ethanol exposure could be linked to ethanol exposure during any single trimester-equivalent. Ethanol exposure during the 1^st or 3^rd trimester-equivalent produced only minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2^nd trimester equivalent resulted in a pronounced decrease in long-term potentiation, indicating that the timing of exposure influences the severity of the deficit. Together, the results from these experiments demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure and dependent on the timing of exposure. Furthermore, these results allude to neural circuit malfunction within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.     

Disappearance of prostaglandins F2α and 15-methyl F2α from amniotic fluid as measured by radioimmunoassay

A sensitive and relatively specific radioimmunoassay for 15 (S) 15 methyl prostaglandin F_2α was used to determine the levels of the drug in amniotic fluid after it had been injected intra-amniotically for termination of second trimester pregnancy. The disappearance of the free acid (tham salt) and methyl ester of the prostaglandin analogue were similar. The results of this preliminary study suggest that the drug rapidly equilibrates in the fluid and this is followed by a slow removal from the amniotic sac. A comparison with a similar study with PGF_2α, revealed that the analogue had a longer half-life in the amniotic fluid.