79 UTERINE AND PLACENTAL INTERACTIONS DURING NECROTIC TIP DEVELOPMENT IN THE PIG FROM DAY 22 TO 42 OF GESTATION

2014 ◽  
Vol 26 (1) ◽  
pp. 153
Author(s):  
E. C. Wright ◽  
J. R. Miles ◽  
C. A. Lents ◽  
L. A. Rempel

Placental development is important for fetal development and nutrient and waste transport. The pig, a litter bearing animal, has an epitheliochorial placenta that forms a noninvasive attachment with the uterine endometrium. Insufficient placental development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Necrotic tips develop at the distal ends of each allantochorion between Day 22 and 42 of gestation. During this same period, placenta attaches to the uterine endometrium and establish fetal blood supplies and nutrient exchange. The attached placenta is composed of a central highly vascular placental (HVP) region adjacent to the fetus and less vascular placental (LVP) regions on either side to the fetus, the paraplacenta and necrotic tips, which form after 27 days of gestation. The objective of this study was to comprehensively evaluate uterine–placental interactions and necrotic tip development from 22 to 42 days of gestation in the gilt. Gilts (n = 25) were bred by AI at first detection of oestrus (Day 0) and harvested at 22, 27, 32, 37, or 42 days of gestation. Each conceptus was counted and weighed to identify the large, medium, and small fetus in each litter. From these fetuses, HVP and LVP sections of tissue and necrotic tip (no placental attachment) were collected. Intact attached uterus and placenta were collected for histology and preserved in paraformaldehyde. Placentas were then stripped from the endometrium and individually weighed. Hematoxylin and eosin staining of uterine : placental sections was used to identify uterine fold development in the HVP, LVP, and uterine endometrial morphology in the necrotic tip regions. Three folds were measured for depth, width, and area using BQ Nova Prime software (Bioquant Image Analysis, Nashville, TN, USA). Data were analysed using PROC MIXED in SAS (SAS Institute Inc., Cary, NC, USA). Litter size, 12.1 ± 3.4, was similar (P = 0.86) for all days of gestation. Fetal and placental weight increased (P < 0.05) as day of gestation increased. Average fetal weight was similar (P = 0.30) for Day 27 and 32 with a tendency (P = 0.09) to increase by Day 37 before a significant increase at Day 42 (P = 0.002). The placenta increased (P = 0.02) in weight throughout this period of gestation, with the greatest increase in weight between 37 and 42 days of gestation. The LVP zones had no measureable fold formation until Day 32 from most conceptuses, and all LVP zones displayed microfold formation by Day 37. Necrotic tips became apparent after 27 days of gestation. Necrotic tip areas of the uterus had observable modifications from Day 32 to 42 of gestation, developing folds with dramatic changes in endometrial cell size and morphology. This work demonstrated fundamental time points in placental development that correspond to fetal growth and microfold formation. Gestation Day 27 through 32 show limited changes in either fetal growth or increased placental weight; however, significant morphological changes occur throughout the placenta, and even necrotic tips demonstrating the dynamic architecture of the establishing porcine placenta during early gestation.

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 180-193 ◽  
Author(s):  
Erica D. Watson ◽  
James C. Cross

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 755-755
Author(s):  
Olivia Gutherz ◽  
Jia Chen ◽  
Qian Li ◽  
Maya Deyssenroth ◽  
Neil Dodge ◽  
...  

Abstract Objectives Imprinted genes are epigenetically regulated and play critical roles in placental development and fetal growth. We aimed to examine (1) the impact of maternal one-carbon (methyl donor) nutrition on placental imprinted gene expression, placental development, and fetal growth; (2) whether imprinted gene expression alterations mediate effects of one-carbon nutrition on placental development and fetal growth; (3) interaction effects between one-carbon nutrients and imprinted genes in placental development and fetal growth. Methods Histopathology and expression of 109 imprinted genes (Nanostring) were assessed in placentas from 101 women recruited at initiation of antenatal care in a prospective cohort study examining developmental effects of prenatal alcohol exposure in South Africa. Women were interviewed prenatally about demographics, alcohol, smoking, and drug use, and erythrocyte folate, serum vitamin B12, and plasma choline concentrations were assayed at recruitment. Infant weight and height were assessed at age 2 wk. Results In limma tests, women with plasma choline concentrations below the median had lower placental expression of EPS15, IGF2R, LINC00657, SGCE, ZC3H12C, and ZNF264 than women above the median (p &lt; .05, FDR &lt; .10). In regression models adjusted for potential confounders (maternal age, gravidity, education, alcohol and drug use), plasma choline (μM) was associated with larger placental weight (g) (B = 14.0(1.9, 26.2)) and reduced maternal vascular underperfusion (MVU) prevalence (B = −.07(−.12, −.02). In causal inference analyses, there were trends for mediation of the relation between choline and MVU by decreased LINC00657, ZC3H12C, and ZNF264 expression. In regression models examining plasma choline X imprinted gene expression interaction effects, choline modified relations of EPS15, ZC3H12C, and ZNF264 to placental weight and fetal growth. Conclusions Maternal plasma choline was associated with decreased placental expression of 6 imprinted genes, 3 of which may mediate effects of choline on placental development. Choline modified effects of 3 genes on placental and fetal growth. These findings suggest maternal choline status may impact placental and fetal development, with imprinted genes playing mechanistic roles. Funding Sources NIH/NIAAA; Lycaki-Young Fund.


Author(s):  
Kathrin A. Dunlap ◽  
Bryan G. White ◽  
David W. Erikson ◽  
M. Carey Satterfield ◽  
Christiane Pfarrer ◽  
...  

Abstract Background The lysosphingolipid, sphingosine-1-phosphate, is a well-described and potent pro-angiogenic factor. Receptors, as well as the sphingosine phosphorylating enzyme sphingosine kinase 1, are expressed in the placentomes of sheep and the decidua of rodents; however, a function for this signaling pathway during pregnancy has not been established. The objective of this study was to investigate whether sphingosine-1-phosphate promoted angiogenesis within the placentomes of pregnant ewes. Ewes were given daily jugular injections of FTY720 (2-amino-2[2-(− 4-octylphenyl)ethyl]propate-1,3-diol hydrochloride), an S1P analog. Results FTY720 infusion from days 30 to 60 of pregnancy did not alter maternal organ weights nor total number or mass of placentomes, but did alter placentome histoarchitecture. Interdigitation of caruncular crypts and cotyledonary villi was decreased, as was the relative area of cotyledonary tissue within placentomes. Also, the percentage of area occupied by cotyledonary villi per unit of placentome was increased, while the thickness of the caruncular capsule was decreased in ewes treated with FTY720. Further, FTY720 infusion decreased the number and density of blood vessels within caruncular tissue near the placentome capsule where the crypts emerge from the capsule. Finally, FTY720 infusion decreased asparagine and glutamine in amniotic fluid and methionine in allantoic fluid, and decreased the crown rump length of day 60 fetuses. Conclusions While members of the sphingosine-1-phosphate signaling pathway have been characterized within the uteri and placentae of sheep and mice, the present study uses FTY720 to address the influence of S1P signaling on placental development. We present evidence that modulation of the S1P signaling pathway results in the alteration of caruncular vasculature, placentome architecture, abundance of amino acids in allantoic and amniotic fluids, and fetal growth during pregnancy in sheep. The marked morphological changes in placentome histoarchitecture, including alteration in the vasculature, may be relevant to fetal growth and survival. It is somewhat surprising that fetal length was reduced as early as day 60, because fetal growth in sheep is greatest after day 60. The subtle changes observed in the fetuses of ewes exposed to FTY720 may indicate an adaptive response of the fetuses to cope with altered placental morphology.


Author(s):  
Torri D. Metz ◽  
Amanda A. Allshouse ◽  
Halit Pinar ◽  
Michael Varner ◽  
Marcela C. Smid ◽  
...  

Objective Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. Study Design This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case–control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. Results Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR (p = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses. Conclusion Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth. Key Points


2017 ◽  
Vol 66 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Ram R Kalagiri ◽  
Niraj Vora ◽  
Jessica L Wilson ◽  
Syeda H Afroze ◽  
Venkata N Raju ◽  
...  

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan’s post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.


2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii90-iii91
Author(s):  
Gabriela Barrientos ◽  
Ana Uceda ◽  
Jorge Toblli

Author(s):  
Irene Maria Beune ◽  
Stefanie Elisabeth Damhuis ◽  
Wessel Ganzevoort ◽  
John Ciaran Hutchinson ◽  
Teck Yee Khong ◽  
...  

Context.— Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborn are heterogeneous. Objectives.— To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death. Design.— A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm. Results.— Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery. Conclusions.— A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies.


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