Second Half Of Gestation Research Articles

PSVIII-17 Assessment of conformational changes across three parities in sows

Abstract Conformation-based sow selection is performed prior to reaching mature size, yet little is known about how conformation changes as growth continues. To assess conformation changes, 9 conformational traits were objectively measured at 12 discrete time points between 112 d of age and parity 3 weaning on 622 sows in 5 cohorts. The 9 traits included 5 body size traits (body length, body depth at the shoulder and flank, and height at the shoulder and flank) and 4 joint angles (knee, hock, and front and rear pastern). Data were analyzed with a repeated measures model (SAS V 9.4) including cohort and time point as fixed effects, sire as a random effect, and heterogeneous compound symmetry as the covariance structure. Sire variance ranged from 0.16 (body depth shoulder) to 2.00 (body length) cm2 for body size traits and 2.28 (rear pastern) to 4.22 (front pastern) degrees2 for joint angles. Cohort had an effect on all traits (P < 0.05). All traits displayed changes over time (P < 0.001). Size traits increased between 112 d of age and parity 3 weaning (64.16 vs. 107.57 cm, 26.62 vs. 44.14 cm, 23.32 vs. 36.92 cm, 46.10 vs. 73.55 cm, 49.36 vs. 77.47 cm for body length, body depth shoulder and flank, and height shoulder and flank, respectively); however, they fluctuated within parity by increasing during gestation and decreasing at weaning. Knee angle decreased (164.12 vs. 150.72 degrees) while fluctuating within parity by decreasing in the second half of gestation and increasing after weaning. Front and rear pastern angles decreased over time (60.89 vs. 53.74 degrees and 64.64 vs. 55.50 degrees for front and rear pastern, respectively), while biologically negligible change was observed in hock angle (148.63 vs. 147.48 degrees). Sow conformation changes throughout life, and these changes may require consideration when making selection decisions.

Association of gestational age with MRI-based biometrics of brain development in fetuses

BackgroundReported date of last menstrual period and ultrasonography measurements are the most commonly used methods for determining gestational age in antenatal life. However, the mother cannot always determine the last menstrual period with certainty, and ultrasonography measurements are accurate only in the first trimester. We aimed to assess the ability of various biometric measurements on magnetic resonance imaging (MRI) in determining the accurate gestational age of an individual fetus in the second half of gestation.MethodsWe used MRI to scan a total of 637 fetuses ranging in age from 22 to 40 gestational weeks. We evaluated 9 standard fetal 2D biometric parameters, and regression models were fitted to assess normal fetal brain development. A stepwise linear regression model was constructed to predict gestational age, and measurement accuracy was determined in a held-out, unseen test sample (n = 49).ResultsA second-order polynomial regression model was found to be the best descriptor of biometric measures including brain bi-parietal diameter, head circumference, and fronto-occipital diameter in relation to normal fetal growth. Normal fetuses showed divergent growth patterns for the cerebrum and cerebellum, where the cerebrum undergoes rapid growth in the second trimester, while the cerebellum undergoes rapid growth in the third trimester. Moreover, a linear model based on biometrics of brain bi-parietal diameter, length of the corpus callosum, vermis area, transverse cerebellar diameter, and cerebellar area accurately predicted gestational age in the second and third trimesters (cross-validation R2 = 0.822, p < 0.001).ConclusionsThese results support the use of MRI biometry charts to improve MRI evaluation of fetal growth and suggest that MRI biometry measurements offer a potential estimation model of fetal gestational age in the second half of gestation, which is vital to any assessment of pregnancy, fetal development, and neonatal care.

Non-invasive cardiovascular assessment of pregnancy in healthy female cats

IntroductionThe aim of this study was to evaluate cardiac morphology, indices of systolic and diastolic function, systolic blood pressure (SBP), and uterine artery resistance index (RI) during normal feline pregnancy. Animals; Materials and MethodsTwenty domestic short-hair pregnant queens, weighing 2.4–3.9 kg. Animals were assessed by two-dimensional, M-mode, and Doppler echocardiography, non-invasive SBP measurement, and uterine Doppler ultrasound every 10 days from mating to parturition. ResultsInterventricular septal thickness at end-diastole and end-systole, left ventricular internal dimension at end-diastole, left ventricular free wall thickness at end-diastole and end-systole, fractional shortening, stroke volume, cardiac output (CO), heart rate, and peak velocities of early and late diastolic transmitral flow increased during the second half of gestation, while SBP and RI decreased during the same period (p < 0.01). Discussion and ConclusionsCardiac structure and function varied during normal pregnancy in these queens. Eccentric hypertrophy, increased indices of systolic function, and increased measurements of CO seem to be the consequences of the hemodynamic modifications occurring during pregnancy. The assessment of maternal cardiovascular function may prove a useful screening tool to detect pregnancy complications in feline species.

Non-invasive measurement of biochemical profiles in the healthy fetal brain

Proton magnetic resonance spectroscopy (1H-MRS) of the fetal brain can be used to study emerging metabolite profiles in the developing brain. Identifying early deviations in brain metabolic profiles in high-risk fetuses may offer important adjunct clinical information to improve surveillance and management during pregnancy. ObjectiveTo investigate the normative trajectory of the fetal brain metabolites during the second half of gestation, and to determine the impact of using different Cramer-Rao Lower Bounds (CRLB) threshold on metabolite measurements using magnetic resonance spectroscopy. Study designWe prospectively enrolled 219 pregnant women with normal fetal ultrasound and biometric measures. We performed a total of 331 fetal 1H-MRS studies with gestational age in the rage of 18–39 weeks with 112 of the enrolled participants scanned twice. All the spectra in this study were acquired on a GE 1.5 T scanner using long echo-time of 144 ​ms and analyzed in LCModel. ResultsWe successfully acquired and analyzed fetal 1H-MRS with a success rate of 93%. We observed increases in total NAA, total creatine, total choline, scyllo inositol and total NAA-to-total choline ratio with advancing GA. Our results also showed faster increases in total NAA and total NAA-to-total choline ratio during the third trimester compared to the second trimester. We also observed faster increases in total choline and total NAA in female fetuses. Increasing the Cramer-Rao lower bounds threshold progressively from 100% to 40%–20% increased the mean metabolite concentrations and decreased the number of observations available for analysis. ConclusionWe report serial fetal brain biochemical profiles in a large cohort of health fetuses studied twice in gestation with a high success rate in the second and third trimester of pregnancy. We present normative in-vivo fetal brain metabolite trajectories over a 21-week gestational period which can be used to non-invasively measure and monitor brain biochemistry in the healthy and high-risk fetus.

Temporal Patterns of Emergence and Spatial Distribution of Sulcal Pits During Fetal Life.

Sulcal pits are thought to represent the first cortical folds of primary sulci during neurodevelopment. The uniform spatial distribution of sulcal pits across individuals is hypothesized to be predetermined by a human-specific protomap which is related to functional localization under genetic controls in early fetal life. Thus, it is important to characterize temporal and spatial patterns of sulcal pits in the fetal brain that would provide additional information of functional development of the human brain and crucial insights into abnormal cortical maturation. In this paper, we investigated temporal patterns of emergence and spatial distribution of sulcal pits using 48 typically developing fetal brains in the second half of gestation. We found that the position and spatial variance of sulcal pits in the fetal brain are similar to those in the adult brain, and they are also temporally uniform against dynamic brain growth during fetal life. Furthermore, timing of pit emergence shows a regionally diverse pattern that may be associated with the subdivisions of the protomap. Our findings suggest that sulcal pits in the fetal brain are useful anatomical landmarks containing detailed information of functional localization in early cortical development and maintaining their spatial distribution throughout the human lifetime.

Pregnancy facilitates maternal liver regeneration after partial hepatectomy.

Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection without terminating pregnancy in some cases. However, how pregnancy affects maternal liver regeneration remains elusive. We performed 70% partial hepatectomy (PH) in nonpregnant mice and gestation day 14 mice, and histologically and molecularly compared their liver regrowth during the next 4 days. We found that compared with the nonpregnant state, pregnancy altered the molecular programs driving hepatocyte replication, indicated by enhanced activities of epidermal growth factor receptor and STAT5A, reduced activities of cMet and p70S6K, decreased production of IL-6, TNFα, and hepatocyte growth factor, suppressed cyclin D1 expression, increased cyclin A1 expression, and early activated cyclin A2 expression. As a result, pregnancy allowed the remnant hepatocytes to enter the cell cycle at least 12 h earlier, increased hepatic fat accumulation, and enhanced hepatocyte mitosis. Consequently, pregnancy ameliorated maternal liver regeneration following PH. In addition, a report showed that maternal liver regrowth after PH is driven mainly by hepatocyte hypertrophy rather than hyperplasia during the second half of gestation in young adult mice. In contrast, we demonstrate that maternal liver relies mainly on hepatocyte hyperplasia instead of hypertrophy to restore the lost mass after PH. Overall, we demonstrate that pregnancy facilitates maternal liver regeneration likely via triggering an early onset of hepatocyte replication, accumulating excessive liver fat, and promoting hepatocyte mitosis. The results from our current studies enable us to gain more insights into how maternal liver regeneration progresses during gestation.NEW & NOTEWORTHY We demonstrate that pregnancy may generate positive effects on maternal liver regeneration following partial hepatectomy, which are manifested by early entry of the cell cycle of remnant hepatocytes, increased hepatic fat accumulation, enhanced hepatocyte mitosis, and overall accelerated liver regrowth.

Calorie restriction during gestation affects ovarian reserve in offspring in the mouse.

The aim of this study was to investigate the effect of calorie restriction (CR) during pregnancy in mice on metabolism and ovarian function in the offspring. Pregnant female mice were divided into two groups, a control group and a CR group (n=7 in each). Mice in the CR group were fed 50% of the amount consumed by control females from Day 10 of gestation until delivery. After weaning, the offspring received diet ad libitum until 3 months of age, when ovaries were collected. Ovaries were serially cut and every sixth section was used for follicle counting. Female offspring from CR dams tended to have increased bodyweight compared with offspring from control females (P=0.08). Interestingly, fewer primordial follicles (60% reduction; P=0.001), transitional follicles (P=0.0006) and total follicles (P=0.006) were observed in offspring from CR mothers. The number of primary, secondary and tertiary follicles did not differ between the groups (P>0.05). The CR offspring had fewer DNA double-strand breaks in primary follicle oocytes (P=0.03). In summary, CR during the second half of gestation decreased primordial ovarian follicle reserve in female offspring. These findings suggest that undernutrition during the second half of gestation may decrease the reproductive lifespan of female offspring.

Physiological development of the equine fetus during late gestation.

In many species, the pattern of growth and physiological development in utero has an important role in determining not only neonatal viability but also adult phenotype and disease susceptibility. Changes in fetal development induced by a range of environmental factors including maternal nutrition, disease, placental insufficiency and social stresses have all been shown to induce adult cardiovascular and metabolic dysfunction that often lead to ill health in later life. Compared to other precocious animals, much less is known about the physiological development of the fetal horse or the longer-term impacts on its phenotype of altered development in early life because of its inaccessibility in utero, large size and long lifespan. This review summaries the available data on the normal metabolic, cardiovascular and endocrine development of the fetal horse during the second half of gestation. It also examines the responsiveness of these physiological systems to stresses such as hypoglycaemia and hypotension during late gestation. Particular emphasis is placed on the role of the equine placenta and fetal endocrine glands in mediating the changes in fetal development seen towards term and in response to nutritional and other environmental cues. The final part of the review presents the evidence that the early life environment of the horse can alter its subsequent metabolic, cardiovascular and endocrine phenotype as well as its postnatal growth and bone development. It also highlights the immediate neonatal environment as a key window of susceptibility for programming of equine phenotype. Although further studies are needed to identify the cellular and molecular mechanisms involved, developmental programming of physiological phenotype is likely to have important implications for the health and potential athletic performance of horses, particularly if born with abnormal bodyweight, premature or dysmature characteristics or produced by assisted reproductive technologies, indicative of an altered early life environment.

Prenatal Identification of Restrictive and Non-restrictive Ventricular Septal Defects Based on End-Systolic Flow Patterns in the Fetal Aortic Isthmus.

Fetuses with large ventricular septal defects (VSDs) must be closely monitored during the perinatal period. Intrauterine assessment of size of septal defects with bidimensional echocardiography are unreliable. The objective of the present study is to document the contribution of flow pattern analysis in the fetal aortic isthmus for prenatal identification of large non-restrictive VSDs requiring immediate postnatal attention. We conducted a cross-sectional retrospective study of Doppler recordings from patients referred to our Fetal Cardiology Unit and diagnosed with one or multiple VSDs from January 2006 to November 2015. Three groups were defined: (1) large non-restrictive VSDs (n = 11) with postnatal cardiac failure (2) small restrictive VSDs (n = 28) asymptomatic, and (3) absence of cardiac abnormality (n = 66). The Isthmic end-Systolic Index (ISI) was computed to quantify aortic isthmus flow and compared between the three groups. Fetuses with restrictive VSD and control group showed similar ISI: stable at 0.20 ± 0.01 up to 27weeks of gestation and dropping later due to the fall of end-systolic velocities in the aortic isthmus. By 35weeks, a brief end-systolic retrograde flow was present, associated with a further fall of ISI down to -0.26 ± 0.05. In contrast, ISI of fetuses with large non-restrictive VSDs were unchanged throughout gestation (0.18 ± 0.06), becoming significantly higher during the last weeks of gestation compared to the two other groups (p < 0.001). In fetuses with VSDs, the ISI measurement from the aortic isthmus Doppler flow during the second half of gestation is a reliable predictor of a large non-restrictive defect with risk of major postnatal clinical impact.

Back pain and functional status in patients with ankylosing spondylitis during pregnancy

Inflammatory rhythm back pain and enthesitis are one of the main clinical manifestations of ankylosing spondylitis (AS), which increase in severity during pregnancy. However, addition of back pain and, possibly, enthesis in the second half of gestation, which is associated with normal pregnancy, needs to make a differential diagnosis for clarifying the genesis of pain and choosing the right management tactics, which determines the relevance of this study.Objective: to investigate the course of pain in the back, enthesis, and inguinal region, as well as the functional status in AS patients during pregnancy and to reveal clinical signs that most accurately reflect inflammatory activity during gestation.Patients and methods. A study included 36 pregnant women with a reliable diagnosis of AS according to the modified New York criteria (1984). Their mean age was 31.6±4.8 years, the mean age at the onset of AS was 21.8±10.9 years; the duration of the disease was 134.9±89.3 months. A control group comprised 30 healthy pregnant women with no history of back pain and arthritis; their mean age was 28.2±4.5 years. The pregnant women of both groups were matched for parity. They made visits at 10–11, 20–21, and 31–32 weeks of pregnancy. Pain intensity was estimated using the numerical pain rating scale (NPRS) and the functional status was assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used to assess enthesitis.Results and discussion. During pregnancy, 94% of AS patients had back pain; its intensity by trimesters was 3 [2; 4], 4 [3; 5.5], 3 [2; 7] and was higher than in healthy pregnant women (p&lt;0.0001). In the study group, there was a rise in pain intensity at night with increasing gestational age (n=23–28): 2 [1; 4] in the first trimester; 3 [0; 5] II in the second trimester; 3 [1; 6] in the third trimester (p&lt; when comparing the first, second, and third trimesters) and an increase in the duration of morning stiffness (n= ): 10 [5; 20], 15 [10; 55], and 15 [5; 60] min, respectively. Moreover, the number of women who reported improvements after exercise (85–63%) and no improvement at rest (88–56%) declined (p&lt;0.05 when comparing the first, second, and third trimesters).In the control group, 1 and 3 patients had morning back stiffness and night pain, respectively. The healthy pregnant women more frequently reported a reduction in back pain after exercise in the third trimester (66.7% of those with pain) than in the first trimester (20% of those with pain) (p&lt;0.05).By the third trimester, the patients with AS showed a change in the nature of back pain: 43.7% of the patients reported an improvement at rest; 42.4% noted an increase in pain after exercise, while the frequency of elements of mechanical back pain was less than that in the control group (p &lt; 0.05).The intensity of groin pain (2.4±1.9, 3.3±2.4, and 4.3±3.0 in the first, second, and third trimesters, respectively) did not differ in AS patients with and without coxitis or pelvic enthesitis. The frequency of enthesitis and MASES scores in the study group were higher than in the control group (p&lt;0.05), the MASES scores increased with gestational age, amounting to 0 [0; 1] in the first trimester and 2 [0; 3] in the third trimester (p&lt;0.05).Functional disorders during pregnancy increased in both groups; there was a difference in BASFI scores between the groups only in the third trimester: 3.5±2.8 and 1.7±1.2, respectively (p&lt;0.05).Conclusion. Back pain and functional disorders increase in AS patients during gestation. Night back pain, morning stiffness, and enthesitis reflect the inflammatory activity of AS during pregnancy. Mechanical back pain joins in 40% of women with AS in the third trimester. The criteria for inflammatory back pain and BASFI require adaptation when used in pregnant women.

Office blood pressure values and the necessity of out-of-office measurements in high-risk pregnancies.

To determine if there is an office blood pressure (BP) value below which out-of-office measurements are unnecessary in high-risk pregnant women. We conducted a prospective cohort study in women in the second half of high-risk pregnancies. Office BP measurements and ambulatory blood pressure monitoring (ABPM) was performed. The cohort was divided according to quartiles of office BP and in normotension, white-coat hypertension, masked hypertension and sustained hypertension. The risks for preeclampsia/eclampsia for each category were estimated. Three hundred seventy-three women (30 ± 7 years with 32 ± 4 weeks of gestation) were included; 69 women (18.5%) developed preeclampsia/eclampsia. Risk for preeclampsia/eclampsia increased in a stepwise manner through quartiles of systolic office BP (8.8, 13.4, 19.6 and 32.3%, P < 0.001) and diastolic office BP (6.5, 13.7, 19.6 and 34,4%, P < 0.001). OR increased significantly through quartiles of systolic (P = 0.004) and diastolic (P < 0.001) office BP; the significance becomes evident between the second and third quartile, the cut-off point between these was 125/76 mmHg. Prevalence of white-coat and masked hypertension were 3.8 and 24.7%, respectively. Using ABPM, 14/61 office hypertensive women were reclassified as white-coat hypertension but 92/312 normotensive women as masked hypertension. OR for preeclampsia/eclampsia increased significantly in women with masked hypertension. Absolute risk for preeclampsia/eclampsia in women with office BP less than 125/75 mmHg was similar than that in women with normal ABPM, 7.2 and 7.1%, respectively. Masked hypertension was a prevalent and high-risk condition. Office BP at least 125/75 mmHg in the second half of gestation seems appropriate to indicate out-of-office measurements in high-risk pregnancies.

Natural embryonic death in the plain viscacha Lagostomus maximus: are there previous anatomo-histological variations that would intervene in the differential survival of the implantations?

Visualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal gadolinium contrast agent (liposomal-Gd).Studies were performed in fifteen pregnant C57BL/6 mice at 10, 12, 14, 16, and 18 days of gestation. MRI was performed on a 1T permanent magnet scanner. Pre-contrast and post-contrast images were acquired using T1-weighted gradient-recalled echo (T1w-GRE) and T2-weighted fast spin echo (T2w-FSE) sequences. Animals were euthanized after imaging and feto-placental units harvested for histological examination. Visualization of the RPCS was scored by a maternal-fetal radiologist and quantified by measuring the contrast-to-noise ratio (CNR) on T1w images. Feto-placental features were segmented for analysis of volumetric changes during gestation.Contrast-enhanced T1w images enabled the visualization of structural changes in placental development between days 10–18 of gestation. Although the placental margin on the fetal side was clearly visible at all time points, the RPCS was partially visible at day 10 of gestation, and clearly visible by day 12. Hematoxylin and eosin (H&E) staining of the placental tissue corroborated MRI findings of structural and morphological changes in the placenta.Contrast-enhanced MR imaging using liposomal-Gd enabled adequate visualization of the retroplacental clear space starting at day 12 of gestation. The agent also enabled characterization of placental structure and morphological changes through gestation.

Effect of maternal feed restriction in dairy goats at different stages of gestation on skeletal muscle development and energy metabolism of kids at the time of births

The aim was to determine effects of maternal feed restriction in dairy goats at gestational different stages on skeletal muscle development and energy metabolism in kids at birth. Six pregnant goats were fed 50% of total digestible nutrients (TDN) and crude protein (CP) (NRC, 2007) recommendations in the first half of gestation and then fed to 100% of the recommendations in the second half of gestation (treatment R-M). In the other group, eight pregnant goats were fed 100% of TDN and CP in the first half of gestation and 50% of a restricted diet the second half of gestation (treatment M-R). Birth weight, blood glucose concentration, muscle fiber number, and size of kids at birth were not affected by maternal feed restriction. The mRNA and protein abundance of myogenic, adipogenic and fibrogenic markers were not affected (P > 0.05) by maternal diet. With regard to values for variables in kid energy metabolism, mRNA abundance of the glycolic enzyme HKII was less (P = 0.03) in the M-R group. In conclusion, maternal feed restriction in the first or second half of gestation had no affect mRNA abundance on myogenic, adipogenic, and fibrogenic markers nor were there changes in skeletal muscle mesenchymal stem cell population of kids at the time of birth. There, however, may be detrimental effects on energy metabolism by reducing HKII gene expression in skeletal muscle of dairy goat kids at the time of birth.

Callosal septa express guidance cues and are paramedian guideposts for human corpus callosum development.

The early development and growth of the corpus callosum are supported by several midline transient structures in mammals that include callosal septa (CS), which are present only in the second half of gestation in humans. Here we provide new data that support the guidance role of CS in corpus callosum development, derived from the analysis of 46 postmortem fetal brains, ranging in age from 16 to 40 post conception weeks (PCW). Using immunohistochemical methods, we show the expression pattern of guidance cues ephrinA4 and neogenin, extracellular protein fibronectin, as well as non-activated microglia in the CS. We found that the dynamic changes in expression of guidance cues, cellular and extracellular matrix constituents in the CS correlate well with the growth course of the corpus callosum at midsagittal level. The CS reach and maintain their developmental maximum between 20 and 26 PCW and can be visualized as hypointense structures in the ventral callosal portion with exvivo (invitro) T2-weighted 3T magnetic resonance imaging (MRI). The maximum of septal development overlaps with an increase in the callosal midsagittal area, whereas the slow, gradual resolution of CS coincides with a plateau of midsagittal callosal growth. The recognition of CS existence in human fetal brain and the ability to visualize them by exvivoMRI attributes a potential diagnostic value to these transient structures, as advancement in imaging technologies will likely also enable invivoMRI visualization of the CS in the near future.

Aberrant gyrification contributes to the link between gestational age and adult IQ after premature birth.

Gyrification is a hallmark of human brain development, starting in the second half of gestation in primary cortices, followed by unimodal and then transmodal associative cortices. Alterations in gyrification have been noted in premature-born newborns and children, suggesting abnormal cortical folding to be a permanent feature of prematurity. Furthermore, both gyrification and prematurity are tightly linked with cognitive performance, indicating a link between prematurity, gyrification, and cognitive performance. To investigate this triangular relation, we tested the following two hypotheses: (i) gyrification is aberrant in premature-born adults; and (ii) aberrant gyrification contributes to the impact of prematurity on adult cognitive performance. One hundred and one very premature-born adults (i.e. adults born before 32 weeks of gestation, and/or with birth weight <1500 g) and 111 mature-born adults were assessed by structural MRI and cognitive testing at 27 years of age. Gyrification was measured by local cortical absolute mean curvature (AMC), evaluated through structural MRI. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale, full-scale IQ test. Two-sample t-tests, regression and mediation analyses were used to assess AMC group differences and the relation between AMC, birth-related variables, and full-scale IQ. Three key findings were identified. First, local AMC was widely increased in fronto-temporo-parietal primary and associative cortices of very premature-born adults. Increase of AMC was inversely associated with gestational age and birth weight and positively associated with medical complications at birth, respectively. Second, increased AMC of temporal associative cortices specifically contributed to the association between prematurity and reduced adult IQ (two-path mediation), indicating that aberrant gyrification of temporal associative cortices is critical for impaired cognitive performance after premature birth. Finally, further investigation of the relationship of gyrification between the early folding postcentral cortices and associative temporal cortices, folding later during neurodevelopment, revealed that the effect of gyrification abnormalities in associative temporal cortices on adult IQ is influenced itself by gyrification abnormalities occurring in the early folding postcentral cortices (three-path mediation). These results indicate that gyrification development across cortical areas in the brain conveys prematurity effects on adult IQ. Overall, these results provide evidence that premature birth leads to permanently aberrant gyrification patterns suggesting an altered neurodevelopmental trajectory. Statistical mediation modelling suggests that both aberrant gyrification itself as well as its propagation across the cortex express aspects of impaired neurodevelopment after premature birth and lead to reduced cognitive performance in adulthood. Thus, markers of gyrification appear as potential candidates for prognosis and treatment of prematurity effects.

Increased vasopressin secretion during preeclampsia despite normal plasma osmolality

Preeclampsia (PE) is a cardiovascular disorder that affects 4–7% of pregnancies and typically involves new onset hypertension, proteinuria, and edema. Diagnosis of the disorder is formally performed in the second half of gestation based upon clinical signs, but we and others have discovered that maternal plasma levels of copeptin (CPP, the stable C‐terminal fragment of arginine vasopressin, AVP) are elevated already in the first trimester and are highly predictive of the development of PE. Further, chronic low‐dose AVP infusion is sufficient to model almost all the clinical features of PE in pregnant mice. Our objective is therefore to understand the cause of elevated AVP secretion in human PE. Previous studies indicate that blood volume is reduced during PE, but no change in osmolality has been noted. We therefore hypothesized (i) that plasma AVP levels are elevated in early gestation of pregnancies that later develop PE, and (ii) that elevated AVP and CPP secretion during PE is secondary to altered volume regulation. Blood samples (1st and 2nd trimester) from women who later developed PE or represent clinically‐matched case controls were obtained from the Maternal Fetal Tissue Bank (IRB#200910784) at the University of Iowa. Consistent with our first hypothesis, plasma levels of AVP, assessed by ELISA after Sep‐Pak C18 reversed solid phase extraction, were increased in 1st and 2nd trimester from women who later developed PE (25.5±3.6, n=63 vs 52.1±22.2, n=5 pg/mL, mean±SEM, p=0.01) despite no change in osmolality (279.6±0.7, n=46 vs 277.5±1.2, n=4 mOsm/kg H2O). Plasma sodium was increased in 1st and 2nd trimesters before the onset of PE (133.9±0.6, n=91 vs 138.5±0.6, n=6 mmol/L, p&lt;0.05), but potassium was unchanged (4.13±0.05 vs 4.38±0.14 mmol/L). These findings support the conclusions that (i) AVP levels are indeed increased in early pregnancy before the onset of clinical symptoms of PE, as was suspected based upon previous studies of CPP; that (ii) the defended osmolality set‐point is similar between control and PE pregnancies, and therefore chronically elevated osmolality is unlikely to be the major cause of elevated AVP secretion during PE, and that (iii) offsetting changes in concentrations of individual osmolytes may be present during PE.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Histological and MRI Study of the Development of the Human Indusium Griseum.

To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12-40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14-41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.

Pre-clinical magnetic resonance imaging of retroplacental clear space throughout gestation

IntroductionVisualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal gadolinium contrast agent (liposomal-Gd). Materials and methodsStudies were performed in fifteen pregnant C57BL/6 mice at 10, 12, 14, 16, and 18 days of gestation. MRI was performed on a 1T permanent magnet scanner. Pre-contrast and post-contrast images were acquired using T1-weighted gradient-recalled echo (T1w-GRE) and T2-weighted fast spin echo (T2w-FSE) sequences. Animals were euthanized after imaging and feto-placental units harvested for histological examination. Visualization of the RPCS was scored by a maternal-fetal radiologist and quantified by measuring the contrast-to-noise ratio (CNR) on T1w images. Feto-placental features were segmented for analysis of volumetric changes during gestation. ResultsContrast-enhanced T1w images enabled the visualization of structural changes in placental development between days 10–18 of gestation. Although the placental margin on the fetal side was clearly visible at all time points, the RPCS was partially visible at day 10 of gestation, and clearly visible by day 12. Hematoxylin and eosin (H&E) staining of the placental tissue corroborated MRI findings of structural and morphological changes in the placenta. ConclusionsContrast-enhanced MR imaging using liposomal-Gd enabled adequate visualization of the retroplacental clear space starting at day 12 of gestation. The agent also enabled characterization of placental structure and morphological changes through gestation.

Downregulation of LRb in VMH/DMH during the second half of gestation and upregulation of SOCS-3 in ARC in late-pregnant ewes – Implications for leptin resistance

To investigate factors involved in pregnancy-induced regulation of tissue sensitivity to leptin, we determined leptin concentrations and expression levels of the long form of the leptin receptor (LRb) and suppressor of cytokine signalling (SOCS)-3 in the ventro- and dorsomedial nuclei (VMH/DMH), arcuate nucleus (ARC), median eminence (ME) and anterior pituitary (AP) in 15 Polish Longwool ewes euthanized at 30, 60, 90 and 120 days of pregnancy and before gestation (n = 3 per group). Leptin concentrations increased during the first half of pregnancy, peaked on day 60, and then declined. In the VMH/DMH, LRb mRNA levels decreased from day 60 of pregnancy; in the ARC, LRb mRNA levels remained stable before and throughout pregnancy. LRb expression in the ME was lower in the first two months of pregnancy than before pregnancy (P < 0.01) and peaked at day 90. In the AP, LRb mRNA levels were higher during mid-pregnancy (P < 0.05) than before pregnancy. SOCS-3 expression in the VMH/DMH was higher throughout gestation (P < 0.05) than before pregnancy but was undetectable at day 120. SOCS-3 transcript levels were higher in the ARC (P < 0.05) in late-pregnancy (at day 120) than in non-pregnant ewes. SOCS-3 mRNA levels in the ME were lower at days 30 and 60 (P < 0.05) than at day 120 or before pregnancy. In the AP, SOCS-3 transcription was stable throughout gestation except at day 120, when it increased (P < 0.05). The changes in plasma leptin concentrations during pregnancy, hypothalamic LRb downregulation in the VMH/DMH during the second half of gestation and SOCS-3 upregulation in the ARC in late-pregnant ewes identified here may be essential components of the mechanisms driving ovine leptin insensitivity.

Variations in ductus arteriosus Doppler parameters in different sonographic views during the second half of gestation.

The aim of the present study was to compare the Doppler parameters of the fetal ductus arteriosus (DA) measured in the traditional longitudinal ductal arch (LDA) view and the newly introduced three vessels and trachea (3VT) plane of the fetal upper mediastinum. The peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (TAMXV) and velocity-time integral (VTI) measurements were taken for 52 fetuses with normal growth (including 29 females). The pulsatility index (PI) and resistance index (RI) were calculated. All parameters for each fetus were measured three times by the same sonographer in the LDA and the 3VT view, and the averages were taken to obtain the final value. Differences in the above values obtained from the LDA and 3VT views were analyzed and the correlation between the differences of all indices and the gestational age (GA) was evaluated using Pearson's linear coefficient of correlation. All of the values were characterized as normally distributed continuous variables by homogeneity of variance analysis. Slight increases in the PSV, EDV, TAMXV and VTI determined in the LDA view were identified compared with those in the 3VT view (P<0.05). Furthermore, these increases were identified to be independent of the GA (P>0.05). However, no significant differences in the impedance indices PI and RI were observed between the two sonographic planes (P>0.05). In conclusion, the LDA view provides a better chance than the 3VT view to obtain higher values of velocity parameters (PSV, EDV, TMAXV and VTI) within the fetal DA, and the differences are independent of the GA. However, no significant variations in the impedance indices PI and RI were observed between these two sonographic planes.