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PloS One 2020Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH)... (Clinical Trial)
Clinical Trial
High levels of maternal total tri-iodothyronine, and low levels of fetal free L-thyroxine and total tri-iodothyronine, are associated with altered deiodinase expression and activity in placenta with gestational diabetes mellitus.
Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T3) and L-thyroxine (T4) Hormones had been associated with GDM, but the physiopathological meaning of these alterations is still unclear. Maternal TH cross the placenta through TH Transporters and their Deiodinases metabolize them to regulate fetal TH levels. Currently, the metabolism of TH in placentas with GDM is unknown, and there are no other studies that evaluate the fetal TH from pregnancies with GDM. Therefore, we evaluated the levels of maternal TH during pregnancy, and fetal TH at delivery, and the expression and activity of placental deiodinases from GDM pregnancies. Pregnant women were followed through pregnancy until delivery. We collected blood samples during 10-14, 24-28, and 36-40 weeks of gestation for measure Thyroid-stimulating hormone (TSH), Free T4 (FT4), Total T4 (TT4), and Total T3 (TT3) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT4, TT4, and TT3 in total blood cord at the delivery. Also, we measured the placental expression of Deiodinases by RT-PCR, western-blotting, and immunohistochemistry. The activity of Deiodinases was estimated quantified rT3 and T3 using T4 as a substrate. Mothers with GDM showed higher levels of TT3 during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT4, FT4, and TT3; and an increased TSH level in umbilical cord blood from GDM. Placentae from GDM mothers have a higher expression and activity of Deiodinase 3, but lower Deiodinase 2, than NGT mothers. In conclusion, GDM favors high levels of TT3 during all gestation in the mother, low levels in TT4, FT4 and TT3 at the delivery in neonates, and increases deiodinase 3, but reduce deiodinase 2 expression and activity in the placenta.
Topics: Adult; Diabetes, Gestational; Female; Gene Expression Regulation, Enzymologic; Humans; Iodide Peroxidase; Placenta; Pregnancy; Thyroxine; Triiodothyronine; Iodothyronine Deiodinase Type II
PubMed: 33232364
DOI: 10.1371/journal.pone.0242743 -
Journal of Visualized Experiments : JoVE Apr 2023The placenta is an essential organ that regulates and maintains mammalian development in utero. The placenta is responsible for the transfer of nutrients and waste...
The placenta is an essential organ that regulates and maintains mammalian development in utero. The placenta is responsible for the transfer of nutrients and waste between the mother and fetus and the production and delivery of growth factors and hormones. Placental genetic manipulations in mice are critical for understanding the placenta's specific role in prenatal development. Placental-specific Cre-expressing transgenic mice have varying effectiveness, and other methods for placental gene manipulation can be useful alternatives. This paper describes a technique to directly alter placental gene expression using CRISPR gene manipulation, which can be used to modify the expression of targeted genes. Using a relatively advanced surgical approach, pregnant dams undergo a laparotomy on embryonic day 12.5 (E12.5), and a CRISPR plasmid is delivered by a glass micropipette into the individual placentas. The plasmid is immediately electroporated after each injection. After dam recovery, the placentas and embryos can continue development until assessment at a later time point. The evaluation of the placenta and offspring after the use of this technique can determine the role of time-specific placental function in development. This type of manipulation will allow for a better understanding of how placental genetics and function impact fetal growth and development in multiple disease contexts.
Topics: Pregnancy; Female; Mice; Animals; Placenta; Clustered Regularly Interspaced Short Palindromic Repeats; Fetal Development; Fetus; Mammals
PubMed: 37125793
DOI: 10.3791/64760 -
Biology of Sex Differences Dec 2022Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can...
BACKGROUND
Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different timepoints throughout pregnancy and comparisons to adult tissues remains poorly characterized.
METHODS
Here, we collect and characterize sex differences in gene expression in term placentas (≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx.
RESULTS
We identify 268 and 53 sex-differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex-differentially expressed genes observed in the term placentas, 31 are also sex-differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex-differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males.
CONCLUSIONS
We find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full-term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.
Topics: Pregnancy; Female; Male; Adult; Humans; Sex Characteristics; Placenta; Pregnancy Trimester, First
PubMed: 36550527
DOI: 10.1186/s13293-022-00470-y -
American Journal of Clinical Pathology Jun 2020To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy.
OBJECTIVES
To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy.
METHODS
Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma.
RESULTS
Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma.
CONCLUSIONS
Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.
Topics: Adult; Betacoronavirus; COVID-19; Case-Control Studies; Coronavirus Infections; Female; Humans; Pandemics; Placenta; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; SARS-CoV-2
PubMed: 32441303
DOI: 10.1093/ajcp/aqaa089 -
Medical Image Analysis Jan 2023Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US...
Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US resulting in highly variable reference annotations, and (iii) the limited field-of-view of US prohibiting whole placenta assessment at late gestation. In this work, we address these three challenges with a multi-task learning approach that combines the classification of placental location (e.g., anterior, posterior) and semantic placenta segmentation in a single convolutional neural network. Through the classification task the model can learn from larger and more diverse datasets while improving the accuracy of the segmentation task in particular in limited training set conditions. With this approach we investigate the variability in annotations from multiple raters and show that our automatic segmentations (Dice of 0.86 for anterior and 0.83 for posterior placentas) achieve human-level performance as compared to intra- and inter-observer variability. Lastly, our approach can deliver whole placenta segmentation using a multi-view US acquisition pipeline consisting of three stages: multi-probe image acquisition, image fusion and image segmentation. This results in high quality segmentation of larger structures such as the placenta in US with reduced image artifacts which are beyond the field-of-view of single probes.
Topics: Humans; Female; Pregnancy; Placenta
PubMed: 36257132
DOI: 10.1016/j.media.2022.102639 -
Reproduction in Domestic Animals =... Sep 2021Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the...
Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the foetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi-quantitative RT-PCR to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. Semi-quantitative RT-PCR was used to define macrophage polarization in foetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1 polarization [interferon regulatory factor-5 (IRF5), interleukin (IL)-12A, IL12B] and in M2 polarization (IL10) were studied. Ultrastructurally, foetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry, macrophages were identified by a strong staining with the lysosomal marker Lysosome-associated membrane glycoprotein 1 (LAMP-1), while myofibroblast in the maternal stroma was positive for alpha-smooth muscle actin. We used the LAMP-1 marker to compare the density of foetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT-PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1-, compared to M2-associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro-inflammatory M1 polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than foetal macrophages.
Topics: Animals; Cattle; Female; Fetus; Macrophages; Parturition; Placenta; Pregnancy; Transcriptome
PubMed: 34174122
DOI: 10.1111/rda.13983 -
Philosophical Transactions of the Royal... Mar 2015The placenta is one of the most morphologically variable mammalian organs. Four major characteristics are typically discussed when comparing the placentas of different... (Review)
Review
The placenta is one of the most morphologically variable mammalian organs. Four major characteristics are typically discussed when comparing the placentas of different eutherian species: placental shape, maternal-fetal interdigitation, intimacy of the maternal-fetal interface and the pattern of maternal-fetal blood flow. Here, we describe the evolution of three of these features as well as other key aspects of eutherian placentation. In addition to interspecific anatomical variation, there is also variation in placental anatomy and function within a single species. Much of this intraspecific variation occurs in response to different environmental conditions such as altitude and poor maternal nutrition. Examinations of variation in the placenta from both intra- and interspecies perspectives elucidate different aspects of placental function and dysfunction at the maternal-fetal interface. Comparisons within species identify candidate mechanisms that are activated in response to environmental stressors ultimately contributing to the aetiology of obstetric syndromes such as pre-eclampsia. Comparisons above the species level identify the evolutionary lineages on which the potential for the development of obstetric syndromes emerged.
Topics: Animals; Biological Evolution; Female; Mammals; Maternal-Fetal Exchange; Obstetric Labor Complications; Placenta; Pregnancy; Species Specificity
PubMed: 25602076
DOI: 10.1098/rstb.2014.0072 -
Placenta Jan 2021Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth...
INTRODUCTION
Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth outcomes in a Canadian cohort of women living with HIV (HIV) on antiretroviral therapy (ART) from conception and HIV-uninfected (HIV) women.
METHODS
Term placentas from 94 women (40 HIV, 54 HIV) were studied. Trimmed placenta weight was collected. Placenta digital photos were used to compute morphometric parameters. Regression models investigated associations between log-transformed placenta parameters and birth outcomes.
RESULTS
We observed a trend towards lower placenta weight and smaller placenta area in the HIV group, both of which were significantly associated with small for gestational age births. HIV serostatus was associated with 6-fold (95%CI 2-20) greater odds of having placenta area in the lowest quartile (<236 cm). Cord marginality (distance from the edge) was significantly lower in the HIV group (p = 0.004), with 35% of placenta having an abnormal (marginal or velamentous) cord insertion vs. 12.5% in the HIV group (p = 0.01). Velamentous cord insertion was seen in 13% of placentas in the HIV vs. 0% in HIV group (p = 0.02). A significant correlation between cord marginality and placenta thickness was observed in the HIV group, with a more marginal cord being associated with a thicker placenta. This correlation was not observed in the HIV group. HIV placentas exposed to protease inhibitors were significantly less circular compared to the HIV group (p = 0.03).
CONCLUSION
Our data suggest that HIV/ART exposure affects placenta morphology and is associated with higher rates of abnormal cord insertion.
Topics: Adult; Anti-Retroviral Agents; Female; HIV Infections; Humans; Infant, Newborn; Placenta; Pregnancy; Umbilical Cord
PubMed: 33310298
DOI: 10.1016/j.placenta.2020.12.004 -
Human Pathology Jul 2022Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure...
Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has been well described. However, whether the characteristic placental pathology persists after the acute phase of the infection is less clear. We retrospectively identified 67 COVID-19-recovered pregnant patients who had placental pathology available. After reviewing the gross and histopathology, we categorized the findings and studied the placentas for evidence of chronic infection by immunohistochemistry for the spike protein of the virus. We found these placentas showed significantly increased prevalence of maternal and a trend towards significance of fetal vascular malperfusion when compared to a control group of placentas examined for the sole indication of maternal group B streptococcal colonization. None of the COVID-19-recovered placentas showed expression of the viral spike protein; therefore, we found no evidence of persistent infection of the placenta in women with a history of COVID-19 during their pregnancy. We conclude that recovery from a SARS-CoV-2 infection during pregnancy puts the pregnancy at risk for specific pathology.
Topics: COVID-19; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35405186
DOI: 10.1016/j.humpath.2022.04.005 -
International Journal of Molecular... Feb 2021Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of... (Review)
Review
Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of multiple diseases, including neurodegenerative diseases, cardiac failure, and renal failure. Aggregates could pose a hazard for cell survival. Cells exhibit three main mechanisms against the accumulation of aggregates: protein refolding by upregulation of chaperones, reduction of protein overload by translational inhibition, and protein degradation by the ubiquitin-proteasome and autophagy-lysosome systems. Deletion of autophagy-related genes reportedly contributes to intracellular protein aggregation in vivo. Some proteins recognized in aggregates in preeclamptic placentas include those involved in neurodegenerative diseases. As aggregates are derived both intracellularly and extracellularly, special endocytosis for extracellular aggregates also employs the autophagy machinery. In this review, we discuss how the deficiency of aggrephagy and/or macroautophagy leads to poor placentation, resulting in preeclampsia or fetal growth restriction.
Topics: Animals; Female; Humans; Lysosomes; Macroautophagy; Placenta; Pre-Eclampsia; Pregnancy; Protein Aggregation, Pathological
PubMed: 33670947
DOI: 10.3390/ijms22052432