Associations between duration of first trimester intrauterine exposure to genocide against the Tutsi and health outcomes in adulthood

Objectives

Hundreds of thousands of Rwandans were conceived during the 1994 genocide against the Tutsi, including thousands conceived by genocidal rape. We explore whether the duration of first trimester exposure to the genocide is associated with variation in adult mental health outcomes in individuals exposed to varying degrees of genocide-related stress in utero.

Materials and Methods

We recruited 30 Rwandans conceived via genocidal rape, 31 Rwandans conceived by genocide survivors not raped, and 30 individuals of Rwandan-descent who were conceived outside of Rwanda at the time of the genocide (control group). Individuals were age- and sex-matched across groups. Adult mental health was assessed through standardized questionnaires for vitality, anxiety, and depression.

Results

Among the genocide only group, a longer duration of first trimester prenatal exposure was associated with higher anxiety scores and lower vitality (both p < 0.010), and higher depression scores (p = 0.051). Duration of first trimester exposure was not associated with any measures of mental health among the genocidal rape or control group.

Discussion

Duration of exposure to genocide in the first trimester of gestation was associated with variation in adult mental health among the genocide only group. The lack of association between duration of first trimester exposure to genocide and adult mental health in the genocidal rape group may reflect the fact that stress associated with conception through rape persisted beyond the genocide period itself, encompassing all of gestation and likely beyond. Geopolitical and community interventions are needed in the context of extreme events during pregnancy to mitigate adverse intergenerational outcomes.     

Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion

Background  

The aim of this study was to examine the invasiveness of first trimester trophoblasts according to the secretion profile of MMP-2 and -9 at different gestational stages, and to test the similarity between primary trophoblast cell-culture and the JAR choriocarcinoma cell-line.     

First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker

Background  

A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model.     

Apoptosis of resident and inflammatory macrophages before and during the inflammatory response of the virgin bovine mammary gland

Background  

Macrophages may play a prominent role in defense of the bovine mammary gland, and their functionality is necessary for successful eradication of bacterial pathogens. In contrast to necrosis, however, apoptosis has not yet been studied in macrophages from bovine mammary glands. Therefore, the aim of this study was to confirm the occurrence of apoptosis in macrophages from resting heifer mammary glands and during the inflammatory response.     

Proteomic identification of Drosophila melanogaster male accessory gland proteins, including a pro-cathepsin and a soluble γ-glutamyl transpeptidase

Background  

In Drosophila melanogaster, the male seminal fluid contains proteins that are important for reproductive success. Many of these proteins are synthesised by the male accessory glands and are secreted into the accessory gland lumen, where they are stored until required. Previous studies on the identification of Drosophila accessory gland products have largely focused on characterisation of male-specific accessory gland cDNAs from D. melanogaster and, more recently, Drosophila simulans. In the present study, we have used a proteomics approach without any sex bias to identify proteins in D. melanogaster accessory gland secretions.     

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.     

Examination of relaxin and its receptors expression in pig gametes and embryos

Background  

Relaxin is a small peptide also known as pregnancy hormone in many mammals. It is synthesized by both male and female tissues, and its secretions are found in various body fluids such as plasma serum, ovarian follicular fluid, utero-oviduct secretions, and seminal plasma of many mammals, including pigs. However, the presence and effects of relaxin in porcine gametes and embryos are still not well-known. The purpose of this study was to assess the presence of relaxin and its receptors RXFP1 and RXFP2 in pig gametes and embryos.     

Programmed cell death in salt glands of <Emphasis Type="Italic">Tamarix aphylla</Emphasis> L.: an electron microscope analysis

Background  

Tamarix aphylla is a halophyte growing in soils rich in NaCl. Leaves of Tamarix aphylla develop numerous salt glands, which initiate, secrete NaCl, become senescent and eventually die, as part of a programmed process. Dead glands are replaced by new ones, so that only active glands exist on the leaves. Most importantly, these glands remove excess NaCl from the tissues, which protects against hyperosmotic phenomena.     

The morphogenesis of spermathecae and spermathecal glands in Drosophila melanogaster

Sperm storage in female insects is important for reproductive success and sperm competition. In Drosophila melanogaster females, sperm viability during storage is dependent upon secretions produced by spermathecae and parovaria. Class III dermal glands are present in both structures. Spermathecal glands are initially comprised of a three-cell unit that is refined to a single secretory cell in the adult. It encapsulates an end-apparatus joining to a cuticular duct passing secretions to the spermathecal lumen. We have examined spermatheca morphogenesis using DIC and fluorescence microscopy. In agreement with a recent study, cell division ceases by 36 h after puparium formation (APF). Immunostaining of the plasma membrane at this stage demonstrates that gland cells wrap around the developing end-apparatus and each other. By 48–60 h APF, the secretory cell exhibits characteristic adult morphology of an enlarged nucleus and extracellular reservoir. A novel finding is the presence of an extracellular reservoir in the basal support cell that is continuous with the secretory cell reservoir. Some indication of early spermathecal gland formation is evident in the division of enlarged cells lying adjacent to the spermathecal lumen at 18 h APF and in cellular processes that bind clusters of cells between 24 and 30 h APF.     

Conserved and divergent patterns of expression of DAZL,VASA and OCT4 in the germ cells of the human fetal ovary and testis

Background  

Germ cells arise from a small group of cells that express markers of pluripotency including OCT4. In humans formation of gonadal compartments (cords in testis, nests in ovary) takes place during the 1st trimester (6–8 weeks gestation). In the 2nd trimester germ cells can enter meiotic prophase in females whereas in males this does not occur until puberty. We have used qRTPCR, Westerns and immunohistochemical profiling to determine which of the germ cell subtypes in the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to play an essential role in germ cell maturation in mice.     

Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined,Quadruple, Serum Integrated and Integrated Tests

Objective

To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.

Design

Nested case-control study.

Setting

Antenatal screening service.

Population or Sample

532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.

Methods

Stored maternal serum samples (−40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests.

Main Outcome Measures

Median PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).

Results

First trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks’ gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR.

Conclusions

First trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.     

Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia

Objective  

To evaluate levels of matrix metalloproteinases (MMP) and their inhibitors (TIMP) in second trimester amniotic fluid of women with hypertensive disorders compared to normotensive women.     

Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis

Background  

Understanding the pathophysiology of chemokine secretion in endometriosis may offer a novel area of therapeutic intervention. This study aimed to identify chemokines differentially expressed in epithelial glands in eutopic endometrium from normal women and those with endometriosis, and to establish the expression profiles of key chemokines in endometriotic lesions.     

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Background

We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage.

Methods

This was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort.

Results

The cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5–12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls.

Conclusion

The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.     

Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

Background

Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.

Methods

We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.

Results

The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07–1.47] to 1.10 [0.94–1.30] in the first, and from 1.26 [1.08–1.47] to 1.10 [0.93–1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children.

Conclusion

The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.     

Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

Background  

Valproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta.     

Integrin-linked kinase can facilitate syncytialization and hormonal differentiation of the human trophoblast-derived BeWo cell line

Background  

In the fusion pathway of trophoblast differentiation, stem villous cytotrophoblast cells proliferate and daughter cells differentiate and fuse with existing syncytiotrophoblast to maintain the multi-nucleated layer. Integrin-linked kinase (ILK) is highly expressed in 1st and 2nd trimester villous cytotrophoblast cells, yet barely detectable in syncytiotrophoblast, thus we examined the potential role of ILK in aiding trophoblast fusion.     

Micronutrient Levels and Supplement Intake in Pregnancy after Bariatric Surgery: A Prospective Cohort Study

Background

Studies report frequent micronutrient deficiencies after bariatric surgery, but less is known about micronutrient levels of pregnant women after bariatric surgery.

Objective

To prospectively evaluate micronutrient levels and supplement intake in pregnancy following bariatric surgery.

Design

A multicenter prospective cohort study including women with restrictive or malabsorptive types of bariatric surgery. Nutritional deficiencies, together with supplement intake, were screened during pregnancy.

Results

The total population included 18 women in the restrictive and 31 in the malabsorptive group. Most micronutrients were depleted and declined significantly during pregnancy. The proportion of women with low vitamin A and B-1 levels increased to respectively 58 and 17% at delivery (P = 0.005 and 0.002). The proportion of women with vitamin D deficiency decreased from 14% at trimester 1 to 6% at delivery (P = 0.030). Mild anemia was found in respectively 22 and 40% of the women at trimester 1 and delivery. In the first trimester, most women took a multivitamin (57.1%). In the second and third trimester, the majority took additional supplements (69.4 and 73.5%). No associations were found between supplement intake and micronutrient deficiencies.

Conclusion

Pregnant women with bariatric surgery show frequent low micronutrient levels. Supplementation partially normalizes low levels of micronutrients.     

Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp.)

Background  

In conifers, terpene synthases (TPSs) of the gymnosperm-specific TPS-d subfamily form a diverse array of mono-, sesqui-, and diterpenoid compounds, which are components of the oleoresin secretions and volatile emissions. These compounds contribute to defence against herbivores and pathogens and perhaps also protect against abiotic stress.