Recent Advances in Pregnancy-Related Complications

A special issue of Reproductive Medicine (ISSN 2673-3897).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 11636

Special Issue Editor


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Guest Editor
Head, Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
Interests: pregnancy-related complications; pathogenesis; diagnosis/prognosis biomarkers; epigenetics; extracellular nucleic acids in maternal circulation; postpartum/postnatal short-term and long-term consequences
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Special Issue Information

Dear Colleagues, 

Preeclampsia, HELLP syndrome, fetal growth restriction, gestational diabetes mellitus, preterm birth (preterm prelabor rupture of membranes and spontaneous preterm labor) and invasive placenta are major complications responsible for maternal and perinatal morbidity and mortality. The elucidation of the molecular mechanisms related to the initiation and onset of severe pregnancy-related complications enables the identification of potential biomarkers for an early stratification of at-risk patients. Additionally, pregnancy-related complications induce long-term metabolic and vascular abnormalities that might increase the overall risk of metabolic, cardiovascular, cerebrovascular, kidney, and other diseases later in life in mothers and their offspring. This Special Issue aims to provide an overview of the latest research on the molecular and cellular mechanisms associated with pregnancy-related complications, as well as the contribution of pregnancy-related complications to the later development of various diseases. This will include the underlying mechanisms, diagnostics/prognostics and treatment strategies associated with pregnancy-related complications and will be of interest to scientists and clinicians working in this quickly expanding area.

Prof. Dr. Ilona Hromadnikova
Guest Editor

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Keywords

  • gestational hypertension
  • preeclampsia
  • HELLP syndrome
  • fetal growth restriction
  • gestational diabetes mellitus
  • preterm birth
  • invasive placenta

Published Papers (4 papers)

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Research

12 pages, 695 KiB  
Article
Predicting the Need for Insulin Treatment: A Risk-Based Approach to the Management of Women with Gestational Diabetes Mellitus
by Anna S. Koefoed, H. David McIntyre, Kristen S. Gibbons, Charlotte W. Poulsen, Jens Fuglsang and Per G. Ovesen
Reprod. Med. 2023, 4(3), 133-144; https://doi.org/10.3390/reprodmed4030014 - 10 Jul 2023
Viewed by 1078
Abstract
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes including large for gestational age infants. Individualizing the management of women with GDM based on the likelihood of needing insulin may improve pregnancy outcomes. The aim of this study is to identify characteristics [...] Read more.
Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes including large for gestational age infants. Individualizing the management of women with GDM based on the likelihood of needing insulin may improve pregnancy outcomes. The aim of this study is to identify characteristics associated with a need for insulin in women with GDM, and to develop a predictive model for insulin requirement. A historical cohort study was conducted among all women with GDM in a singleton pregnancy at Aarhus University Hospital from 2012 to 2017. Variables associated with insulin treatment were identified through multivariable logistic regression. The variables were dichotomized and included in a point scoring system aiming to predict the likelihood of needing insulin. Seven variables were associated with needing insulin: family history of diabetes, current smoker, multiparity, prepregnancy body mass index, gestational age at the oral glucose tolerance test (OGTT), 2-h glucose value at the OGTT and hemoglobin A1c at diagnosis. A risk score was calculated assigning one point to each variable. On ROC analysis, a cut-off value of ≥3 points optimally predicted a requirement for insulin. This prediction model may be clinically useful to predict requirement for insulin treatment after further validation. Full article
(This article belongs to the Special Issue Recent Advances in Pregnancy-Related Complications)
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15 pages, 2745 KiB  
Article
The Autophagy-Lysosomal Machinery Enhances Cytotrophoblast–Syncytiotrophoblast Fusion Process
by Atsushi Furuta, Tomoko Shima, Mihoko Kawaguchi, Akemi Yamaki-Ushijima, Ippei Yasuda, Sayaka Tsuda, Satoshi Yoneda, Kazuma Higashisaka, Shi-Bin Cheng, Kenji Matsumoto, Yasuo Tsutsumi, Surendra Sharma, Shigeru Saito and Akitoshi Nakashima
Reprod. Med. 2022, 3(2), 112-126; https://doi.org/10.3390/reprodmed3020010 - 05 May 2022
Cited by 3 | Viewed by 2623
Abstract
Poor placentation is closely related with the etiology of preeclampsia and may impact fetal growth restriction. For placental developmental growth, we have demonstrated that dysregulation of autophagy, a key mechanism to maintain cellular homeostasis, in trophoblasts contributes to the pathophysiology of preeclampsia, a [...] Read more.
Poor placentation is closely related with the etiology of preeclampsia and may impact fetal growth restriction. For placental developmental growth, we have demonstrated that dysregulation of autophagy, a key mechanism to maintain cellular homeostasis, in trophoblasts contributes to the pathophysiology of preeclampsia, a severe pregnancy complication, associated with poor placentation. It remains, however, unknown whether autophagy inhibition affects trophoblast syncytialization. This study evaluated the effect of autophagy in an in vitro syncytialization method using BeWo cells and primary human trophoblasts (PHT). In this study, we observed that autophagic activity decreased in PHT and BeWo cells during syncytialization. This decreased activity was accompanied by downregulation of the transcription factor, TFEB. Next, bafilomycin A1, an inhibitor of autophagy via suppressing V-ATPase in lysosomes, inhibited hCG production, CYP11A1 expression (a marker of differentiation), p21 expression (a senescence marker), and cell fusion in BeWo cells and PHT cells. Finally, LLOMe, an agent inducing lysosomal damage, also inhibited syncytialization and led to TFEB downregulation. Taken together, the autophagy-lysosomal machinery plays an important role in cytotrophoblast fusion, resulting in syncytiotrophoblasts. As autophagy inhibition contributed to the failure of differentiation in cytotrophoblasts, this may result in the poor placentation observed in preeclampsia. Full article
(This article belongs to the Special Issue Recent Advances in Pregnancy-Related Complications)
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16 pages, 3638 KiB  
Article
Adaptations in the Hippocampus during the Fetal to Neonatal Transition in Guinea Pigs
by Julia C. Shaw, Rebecca M. Dyson, Hannah K. Palliser, Gabrielle K. Crombie, Mary J. Berry and Jonathan J. Hirst
Reprod. Med. 2022, 3(2), 85-100; https://doi.org/10.3390/reprodmed3020008 - 18 Apr 2022
Cited by 1 | Viewed by 2300
Abstract
(Background) The transition from in utero to ex utero life is associated with rapid changes in the brain that are both protective and required for newborn functional activities, allowing adaption to the changing environment. The current study aimed to reveal new insights into [...] Read more.
(Background) The transition from in utero to ex utero life is associated with rapid changes in the brain that are both protective and required for newborn functional activities, allowing adaption to the changing environment. The current study aimed to reveal new insights into adaptations required for normal ongoing brain development and function after birth. (Methods) Time-mated dams were randomly allocated to fetal collection at gestational age 68 or spontaneous term delivery followed by neonatal collection within 24 h of birth. Immunohistochemistry was performed to examine mature myelin formation and neuronal nuclei coverage. RT-PCR was used to quantify the mRNA expression of key markers of the oligodendrocyte lineage, neuronal development, and GABAergic/glutamatergic pathway maturation. (Results) Mature myelin was reduced in the subcortical white matter of the neonate, whilst neuronal nuclei coverage was increased in both the hippocampus and the overlying cortical region. Increased mRNA expression in neonates was observed for oligodendrocyte and neuronal markers. There were also widespread mRNA changes across the inhibitory GABAergic and excitatory glutamatergic pathways in neonates. (Conclusions) This study has identified important adaptations in the expression of key neurodevelopmental structures, including oligodendrocytes and neurons, that may be essential for appropriate transition in neurodevelopment to the postnatal period. Full article
(This article belongs to the Special Issue Recent Advances in Pregnancy-Related Complications)
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12 pages, 272 KiB  
Article
Placental Maternal Vascular Malperfusion Is Associated with Prepregnancy and Early Pregnancy Maternal Cardiovascular and Thrombotic Profiles
by Carole A. McBride, Ira M. Bernstein, Amelia B. Sybenga, Kelley C. McLean, Thomas Orfeo and Maria Cristina Bravo
Reprod. Med. 2022, 3(1), 50-61; https://doi.org/10.3390/reprodmed3010006 - 08 Mar 2022
Cited by 1 | Viewed by 4481
Abstract
Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation [...] Read more.
Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m2, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies. Full article
(This article belongs to the Special Issue Recent Advances in Pregnancy-Related Complications)
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