1.Multi-organ inflammatory phenotypes and transcriptomic characterization in an inflammation-driven mouse model of preeclampsia induced by LPS.
Ning WANG ; Jing-Qiu FENG ; Ying XIE ; Meng-Can SUN ; Qi WANG ; Zhe WANG ; Lu GAO
Acta Physiologica Sinica 2025;77(5):775-791
Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals
;
Female
;
Pregnancy
;
Mice
;
Pre-Eclampsia/genetics*
;
Inflammation
;
Lipopolysaccharides/adverse effects*
;
Disease Models, Animal
;
Transcriptome
;
Placenta/pathology*
;
Phenotype
3.Clinical characteristics and placental pathology analysis of 14 cases of pregnancy with aortic dissection/aortic aneurysm.
Meng Han ZHENG ; Dong CHEN ; Jian Feng SHANG ; Rui LIU ; Hao Tan ZHOU
Chinese Journal of Pathology 2023;52(5):480-485
Objective: To investigate the pathological changes of placenta in pregnant women with aortic dissection/aneurysm and their relationship with clinical features. Methods: The placental samples of 14 pregnant women with aortic dissection/aneurysm diagnosed from January 2012 to October 2021 and 10 normal placental samples of pregnant women from January 2021 to December 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China were selected. Routine H&E staining and immunohistochemistry were used to analyze the histological features under light microscope. The clinical data were also analyzed. Results: The age of 14 pregnant patients with aortic dissection/aneurysm for placental examination ranged from 22 to 38 years (median, 28 years). The gestational ages ranged from 22 to 39 weeks (median, 34 weeks). The pregnancy of second trimester was noted in 2 cases, and the third trimester in 12 cases. All cases were singleton pregnancy. Seven cases were Stanford type A aortic dissection, 6 cases were Stanford type B aortic dissection, and one case was aortic root aneurysm. Four of the pregnant women underwent aortic dissection surgery after caesarean section, three underwent caesarean section after aortic dissection surgery, and seven underwent both caesarean section and aortic dissection procedures. Among the newborns, 2 cases were full-term birth, and 12 cases were premature birth. Twelve cases had alive newborns, and 2 cases stillbirths. Fetal/placental weight ratio (FPR)<10th percentile was in 5 cases and FPR>90th percentile in one case. Compared with the normal group, accelerated villus maturation and distal villus dysplasia were more frequently found in pregnancy with aortic dissection group (P<0.05). There was no significant difference in villi infarction and decidua vascular lesions between the two groups (P>0.05), nor was there correlation between the type of aortic dissection and distal villus dysplasia and accelerated villus maturation of placentas (P>0.05). The number of villous interstitial blood vessels in the placentas of pregnancy with aortic dissection group was significantly fewer than that in the normal control group (P<0.01). Conclusions: There are considerable pathological changes in the placentas of pregnant women with aortic dissection/aneurysm. The main histological features are accelerated villus maturation and distal villus dysplasia, which are manifestations of villous ischemia and hypoxia, and also a part of the placental pathological manifestations of maternal vascular dysperfusion.
Pregnancy
;
Female
;
Infant, Newborn
;
Humans
;
Infant
;
Young Adult
;
Adult
;
Placenta/pathology*
;
Cesarean Section
;
Aortic Dissection/surgery*
;
Gestational Age
;
Aortic Aneurysm/pathology*
4.Solid placental transmogrification of the lung: A case report and literature review.
Xue Mei HA ; Yong Zheng YAO ; Li Hua SUN ; Chun Yan XIN ; Yan XIONG
Journal of Peking University(Health Sciences) 2023;55(2):357-361
Placental transmogrification of the lung (PTL) is a very rare benign lung lesion. There are only about 40 cases reported in the literature. The imaging and histological features of PTL cases in the publication are various, most of which are cystic and a few of which are solid. Being extremely rare, the solid PTL is unknown to major pathologists and surgeons. We reported a case of solid PTL in the anterior mediastinum. The patient was a 52-year-old male with no history of smoking and without symptoms. During physical examination, chest CT revealed a circular low-density lesion with a maximum diameter of 2.9 cm beside the spine in the posterior basal segment of the left lower lobe of the lung. The wedge resection was performed by video-assisted thoracoscopy. Grossly, a round nodule was located underneath the visceral pleura. It was about 3.0 cm×3.0 cm×1.6 cm and the cut surface was grey-red, soft and spongy. Microscopically, the nodule was constituted of papillare, which resembled placental villi at low magnification. The axis of papillae was edema, in which some mild round cells with clear cytoplasm and CD10 positive staining aggregated and transitioned to immature adipocytes and amorphous pink materials deposited with a few of inflammatory cells infiltration. The surface of papillae was covered with disconti-nuous alveolar epithelium. Combined with the typical morphology and immunohistochemical characteristics of CD10 positive, the diagnosis was PTL. The patient was followed up for 1 year without recurrence and discomfort. So far, the pathogenesis of PTL is unclear. The major hypotheses include hamartoma, variant of emphysema and clonal hyperplasia of stromal cells. Based on the study of our case and publication, we speculate that the hyperplasia of stromal cells located in the alveolar septa might be the first step to form the solid PTL. With the progression of the disease, a typical unilateral cystic nodule develops as a result of secondary cystic degeneration due to the occlusive valve effect. Surgery is the only option for diagnosis and treatment of PTL. The clinician should make an individualized operation plan according to the clinical manifestations, location and scope of the lesion, and preserve the surrounding normal lung tissue as much as possible while completely removing the lesion. There is a favorable prognosis.
Male
;
Humans
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Female
;
Pregnancy
;
Middle Aged
;
Hyperplasia/pathology*
;
Placenta/pathology*
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Lung/pathology*
;
Pulmonary Emphysema/surgery*
;
Tomography, X-Ray Computed/methods*
5.Research progress on the effect of mitochondrial and endoplasmic reticulum stress caused by hypoxia during pregnancy on preeclampsia and intrauterine growth restriction.
Hui-Fang LIU ; Ri-Li GE ; Ta-Na WUREN
Acta Physiologica Sinica 2023;75(5):714-726
Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy
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Female
;
Humans
;
Placenta
;
Fetal Growth Retardation/etiology*
;
Pre-Eclampsia/pathology*
;
Reactive Oxygen Species
;
Hypoxia/pathology*
;
Pregnancy Complications/pathology*
;
Endoplasmic Reticulum Stress
6.Advances in in vitro and in vivo models for Listeria monocytogenes placental infection.
Hui YAN ; Mengjie WU ; Qingli DONG ; Zhuosi LI
Chinese Journal of Biotechnology 2023;39(10):3985-4003
Listeria monocytogenes is recognized as a significant foodborne pathogen, capable of causing listeriosis in humans, which is a global public health concern. This pathogen is particularly dangerous for pregnant women, as it can lead to invasive listeriosis in fetuses and neonates, posing a significant threat to both maternal and fetal health. Therefore, establishing suitable in vitro and in vivo models for L. monocytogenes placenta infection, as well as analyzing and exploring the infection process and its pathogenic mechanism, are important approaches to prevent and control L. monocytogenes infection in mothers and infants. In this study, we reviewed the in vitro and in vivo placental models used for studying the infection of L. monocytogenes in maternal and infant, summarized and discussed the advantages and limitations of each model, and explored the potential of in vitro cell models and organoids for the study of L. monocytogenes infection. This paper aims to support the study of the infection pathway and pathogenesis of listeriosis and provide scientific references for the prevention and control of L. monocytogenes infection.
Female
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Humans
;
Pregnancy
;
Listeria monocytogenes
;
Listeriosis/prevention & control*
;
Placenta/pathology*
;
Public Health
;
Infant, Newborn
7.Free sialic acid storage disorders with fetal hydrops in a neonate.
Wei-Ying MAO ; Yue HE ; Lan ZHANG ; Qi-Zhi HE ; Lu-Ming SUN ; Rong ZHANG
Chinese Journal of Contemporary Pediatrics 2023;25(5):546-550
A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.
Infant, Newborn
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Male
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Humans
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Female
;
Pregnancy
;
Hydrops Fetalis/genetics*
;
N-Acetylneuraminic Acid
;
Placenta/pathology*
;
Ascites
8.Autopsies and placental examinations of perinatal fetal deaths: a clinicopathological analysis of 105 cases.
Ai Chun WANG ; Jun Ling XIE ; Ying Nan WANG ; Xiao Fei SUN ; Li Juan LU ; Yun Fei SUN ; Yi Qun GU
Chinese Journal of Pathology 2022;51(5):431-436
Objective: To summarize the clinicopathological factors related to perinatal fetal death and to evaluate importance of fetal autopsy and placental pathology. Methods: The clinicopathological data of 105 perinatal fetal deaths in Beijing Haidian Maternal and Child Health Hospital from November 2012 to December 2020 were retrospectively analyzed. Relevant literature was also reviewed. Results: The maternal age of the deceased fetuses ranged from 22 to 43 years with the average (31.35±4.04 years), and the gestational weeks were 28-40+6 weeks. Among them, 101 were singleton cases and 4 twin cases. 103 fetuses died in uterus and 2 died during delivery. Relevant factors analysis of the 105 perinatal fetal deaths showed that 86 cases (81.9%, 86/105) were related to umbilical cord/placental abnormality, 10 cases (9.5%, 10/105) uterine infection, 6 cases (5.7%, 6/105) fetal factors, 1 case was fetal maternal blood transfusion syndrome, 1 case twin blood transfusion syndrome, and 1 case died of complete uterine rupture. Among the 86 cases related to umbilical cord/placental abnormality, the diagnosis was most often based on the gross examination of placenta. The most common cause of death was umbilical cord torsion with thin root, followed by placental abruption, tight umbilical cord winding, vascular rupture and umbilical cord true knot. The morphology of placenta revealed mainly functional changes. Among the 10 cases related to intrauterine infections, the placenta generally showed lobular placental edema. The morphological characteristics of ascending infection were mainly acute chorioamnionitis, and the morphological characteristics of blood-borne infection were mainly acute or chronic villitis, as well as villous interstitial inflammation. Identification of viral inclusions suggested viral etiology, while the final diagnosis was relied on laboratory testing. Among the 6 cases related to fetal abnormality, the diagnostic value of placenta was limited and the diagnosis could be made with fetal autopsy. Conclusion: The causes of perinatal fetal death are complex, diverse, and often the synergistic result of multiple factors. Fetal autopsy and placental pathology are the key technical means to identify the cause of death and deserve more attention and utilization.
Adult
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Autopsy
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Child
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Female
;
Fetal Death/etiology*
;
Fetus/pathology*
;
Gestational Age
;
Humans
;
Placenta/pathology*
;
Pregnancy
;
Retrospective Studies
;
Young Adult
9.Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore.
Citra Nz MATTAR ; Shirin KALIMUDDIN ; Sapna P SADARANGANI ; Shephali TAGORE ; Serene THAIN ; Koh Cheng THOON ; Eliane Y HONG ; Abhiram KANNEGANTI ; Chee Wai KU ; Grace Mf CHAN ; Kelvin Zx LEE ; Jeannie Jy YAP ; Shaun S TAN ; Benedict YAN ; Barnaby E YOUNG ; David C LYE ; Danielle E ANDERSON ; Liying YANG ; Lin Lin SU ; Jyoti SOMANI ; Lay Kok TAN ; Mahesh A CHOOLANI ; Jerry Ky CHAN
Annals of the Academy of Medicine, Singapore 2020;49(11):857-869
INTRODUCTION:
Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.
METHODS:
Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission.
RESULTS:
Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5).
CONCLUSION
The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology*
;
Adult
;
COVID-19/transmission*
;
COVID-19 Nucleic Acid Testing
;
COVID-19 Serological Testing
;
Cohort Studies
;
Disease Transmission, Infectious/statistics & numerical data*
;
Female
;
Fetal Blood/immunology*
;
Humans
;
Infectious Disease Transmission, Vertical/statistics & numerical data*
;
Live Birth/epidemiology*
;
Maternal Age
;
Milk, Human/virology*
;
Obesity, Maternal/epidemiology*
;
Placenta/pathology*
;
Pregnancy
;
Pregnancy Complications, Infectious/physiopathology*
;
Pregnancy Outcome/epidemiology*
;
Pregnancy Trimester, First
;
Pregnancy Trimester, Second
;
Prospective Studies
;
RNA, Viral/analysis*
;
Risk Factors
;
SARS-CoV-2
;
Severity of Illness Index
;
Singapore/epidemiology*
;
Umbilical Cord/pathology*
;
Young Adult
10.Thick “Swiss Cheese” Appearance of Uterine Endometrium in Postmenopausal Women with Different Gynecologic Conditions
Yuri KO ; Jinha CHUNG ; Sa Ra LEE ; Sung Hoon KIM ; Heedong CHAE ; Byung Moon KANG
Journal of Menopausal Medicine 2019;25(3):158-163
OBJECTIVES: To uncover gynecologic conditions with similar transvaginal sonographic findings of thick uterine endometrium with honeycomb appearance in pre-and postmenopausal women.METHODS: We retrospectively reviewed cases of patients with endometrial tissue biopsy from January 2010 to December 2016. We also collected office flexible hysteroscopic findings and surgical pathologic results. We analyzed data from 393 patients with confirmed endometrial pathology. Among these patients, 69 had transvaginal ultrasonographic images with thick uterine endometrium and honeycomb or “Swiss cheese” appearance.RESULTS: We found gynecologic conditions such as submucosal leiomyoma with degeneration, endometrial polyp, pseudocystic endometrial change associated with tamoxifen use, progesterone associated endometrial change, pyometra, retained placenta, and uterine synechiae manifested with similar thick endometrium with “Swiss cheese” appearance in transvaginal sonographic images. The most common diagnosis in postmenopausal women was atrophic endometritis, followed by endometrial cancer and endometrial polyps. The most common diagnosis in premenopausal women was abnormal uterine bleeding without pathologic conditions.CONCLUSIONS: Sonographic findings of thick uterine endometrium with “Swiss cheese” appearance need to be considered together with a thorough review of the patient's history and chief complaint before making a tentative diagnosis due to the various conditions sharing the feature.
Biopsy
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Diagnosis
;
Endometrial Neoplasms
;
Endometritis
;
Endometrium
;
Female
;
Gynatresia
;
Humans
;
Hyperplasia
;
Leiomyoma
;
Menopause
;
Pathology
;
Placenta, Retained
;
Polyps
;
Progesterone
;
Pyometra
;
Retrospective Studies
;
Tamoxifen
;
Ultrasonography
;
Uterine Hemorrhage

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