-
Blood Advances Jun 2024Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in...
Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in preeclampsia remains controversial. LMWH may convey beneficial effects in preeclampsia independent of their anti-coagulant activity, possibly by inhibiting inflammation. Here we evaluated whether LMWH inhibit placental thrombo-inflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle (EV)-induced and platelet-dependent preeclampsia-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation and improves trophoblast proliferation in-vivo and in-vitro. Moreover, LMWH inhibits platelet independent trophoblast NLRP3 inflammasome activation. Mechanistically, LWMH activates via Heparin binding epidermal growth factor (HBEGF) signaling the PI3-Kinase-AKT pathway in trophoblasts thus preventing inflammasome activation. In human preeclampsia placental explants, inflammasome activation and PI3-Kinase-AKT signaling events were reduced with LMWH treatment compared to those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates preeclampsia-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in preeclampsia and identify a signaling mechanism through which LMWH ameliorates preeclampsia, thus providing a rationale for the use of LMWH in preeclampsia.
PubMed: 38941535
DOI: 10.1182/bloodadvances.2023011895 -
Science Advances Jun 2024Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using...
Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out-of-sample greater than 0.25 for 73% of target genes. We performed siRNA knockdowns of four TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for three of the four TFs. Our final model contained 113,158 interactions across 391 TFs and 7712 target genes and is publicly available. We identified 29 TFs which were significantly enriched as regulators for genes previously associated with preterm birth, and eight of these TFs were decreased in preterm placentas.
Topics: Humans; Placenta; Female; Pregnancy; Gene Regulatory Networks; Transcription Factors; Genome, Human; Transcriptome; Gene Expression Regulation; Gene Expression Profiling
PubMed: 38941464
DOI: 10.1126/sciadv.adf3411 -
Medicine Jun 2024To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were... (Comparative Study)
Comparative Study Observational Study
To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were also compared to predict pregnancy outcomes in addition to hypertension. This retrospective cohort designed study was conducted on 115 pregnant women with PA. The main parameters scanned and recorded from the hospital database and patient medical files. Two groups were classified regarding of presence or absence of hypertension (53 hypertensive, 62 normotensive). Maternal demographical and clinical characteristics (abdominal pain, vaginal bleeding) were recorded. APGAR scores below 5 at 1st and 5th minute, fetal or neonatal death, admission and length of stay in Neonatal Intensive Care Unit were also investigated and compared between the groups. Stillborn to live-born ratio and lower APGAR scores < 5 at 5th minute were significantly higher in hypertensive group than normotensive group (P = .006 and 0.047, respectively). Poor maternal outcomes were detected in the hypertensive group than normotensive group regarding rate of blood transfusion (27/53, 50.9%; 18/62, 29%, respectively, P = .017). More abdominal pain and less vaginal bleeding were seen in PA with HT. Higher lymphocyte count, mean platelet volume, and platelet distribution width were reported in hypertensive group. Poorer maternal and neonatal outcomes of hypertensive patients with PA were detected. These patients should deserve greater attention to assess not only the possible risks associated with abruption but also the accompanying complications.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Abruptio Placentae; Pregnancy Outcome; Infant, Newborn; Apgar Score; Hypertension, Pregnancy-Induced; Hypertension
PubMed: 38941372
DOI: 10.1097/MD.0000000000038633 -
Frontiers in Medicine 2024Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a... (Review)
Review
Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother's placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.
PubMed: 38938382
DOI: 10.3389/fmed.2024.1388481 -
Case Reports in Obstetrics and... 2024Primary extragonadal germ cell tumors (EGCTs) are a very rare clinical encounter most commonly reported in males. Among females, the placenta, pelvis, uterus, brain, and...
INTRODUCTION
Primary extragonadal germ cell tumors (EGCTs) are a very rare clinical encounter most commonly reported in males. Among females, the placenta, pelvis, uterus, brain, and mediastinum are the most common extragonadal sites and predominantly display nondysgerminoma histology. In this report, we present a case of a primary cervical dysgerminoma in a young female patient. . An 18-year-old nulligravid woman presented with a 12-month history of vaginal bleeding and discharge. Routine blood tests and serum levels of tumor markers were within normal limits. The chest X-ray was normal. A high-resolution pelvic MRI showed a well-defined lobulated cervicovaginal mass measuring 8 × 6 × 5 cm expanding into the vaginal canal with mild homogenous contrast enhancement. An incisional biopsy was performed vaginally under anesthesia, and histologic findings were consistent with dysgerminoma. A repeat follow-up pelvic MRI was done and showed a reduction in the size of the mass by more than 70%. The patient was treated with 4 cycles of bleomycin, etoposide, and cisplatin chemotherapy. Additional external pelvic beam radiation treatment was administered for a partial response. After 3 months of radiotherapy, a contrast abdominopelvic CT scan showed a recurrent cervicovaginal mass with extension to the pelvic sidewalls. The patient was initiated with ifosfamide, paclitaxel, and cisplatin (ITP) as second-line chemotherapy for a recurrent germ cell tumor but later died from hydronephrosis, chronic anemia, and sepsis.
CONCLUSION
The uterine cervix is a very unusual site for primary dysgerminoma and can have a very aggressive clinical course. A high index of suspicion and an exhaustive workup are necessary to reach a diagnosis, particularly in a young patient presenting with a cervical lesion.
PubMed: 38938322
DOI: 10.1155/2024/6465387 -
JACC. Advances Jun 2023
PubMed: 38938231
DOI: 10.1016/j.jacadv.2023.100403 -
JACC. Advances Jun 2023Congenital heart disease (CHD) affects 8 in 1,000 live births with significant postnatal implications including growth failure, neurodevelopmental delay, and mortality....
BACKGROUND
Congenital heart disease (CHD) affects 8 in 1,000 live births with significant postnatal implications including growth failure, neurodevelopmental delay, and mortality. The placenta develops concomitantly with the fetal heart. High rates of placental pathology and discordant growth in pregnancies affected by CHD highlight the significance of the fetal-placental-cardiac axis.
OBJECTIVES
This study aimed to characterize the relationship between neonatal birthweight (BW), head circumference, placental weight (PW), and placental pathology in pregnancies affected by CHD. PW:BW provides a surrogate to assess placental efficiency, or nutrient exchange and delivery by the placenta, across CHD phenotypes.
METHODS
Retrospective cohort of 139 live-born singletons with postnatally confirmed CHD with placental pathology. Placental examination, infant BW, head circumference, and CHD categories (septal defects, right-sided defects, left-sided defects, conotruncal anomalies, and others) were included. Chi-square, Fisher's exact, or Kruskall-Wallis tests and multinomial logistic regressions, as appropriate.
RESULTS
Median birthweight and head circumference percentile was 33 and 35, respectively. Placental pathology was documented in 37% of cases. PW to BW ratios were <10th percentile for 78% and <3rd percentile for 54% of the cohort, with no difference between CHD categories ( = 0.39 and = 0.56, respectively).
CONCLUSIONS
Infants with CHD have preserved BW and head circumferences in the setting of small placentas and increased prevalence of placental pathology, suggesting placental efficiency. Detection of abnormal placental growth could add prenatal diagnostic value. Placental and neonatal discordant growth may allude to a vascular anomaly predisposing fetuses to developing CHD. Further studies are needed to explore fetal nutrient delivery and utilization efficiency.
PubMed: 38938228
DOI: 10.1016/j.jacadv.2023.100383 -
Current Topics in Developmental Biology 2024Biomechanics in embryogenesis is a dynamic field intertwining the physical forces and biological processes that shape the first days of a mammalian embryo. From the... (Review)
Review
Biomechanics in embryogenesis is a dynamic field intertwining the physical forces and biological processes that shape the first days of a mammalian embryo. From the first cell fate bifurcation during blastulation to the complex symmetry breaking and tissue remodeling in gastrulation, mechanical cues appear critical in cell fate decisions and tissue patterning. Recent strides in mouse and human embryo culture, stem cell modeling of mammalian embryos, and biomaterial design have shed light on the role of cellular forces, cell polarization, and the extracellular matrix in influencing cell differentiation and morphogenesis. This chapter highlights the essential functions of biophysical mechanisms in blastocyst formation, embryo implantation, and early gastrulation where the interplay between the cytoskeleton and extracellular matrix stiffness orchestrates the intricacies of embryogenesis and placenta specification. The advancement of in vitro models like blastoids, gastruloids, and other types of embryoids, has begun to faithfully recapitulate human development stages, offering new avenues for exploring the biophysical underpinnings of early development. The integration of synthetic biology and advanced biomaterials is enhancing the precision with which we can mimic and study these processes. Looking ahead, we emphasize the potential of CRISPR-mediated genomic perturbations coupled with live imaging to uncover new mechanosensitive pathways and the application of engineered biomaterials to fine-tune the mechanical conditions conducive to embryonic development. This synthesis not only bridges the gap between experimental models and in vivo conditions to advancing fundamental developmental biology of mammalian embryogenesis, but also sets the stage for leveraging biomechanical insights to inform regenerative medicine.
Topics: Animals; Humans; Embryonic Development; Embryo, Mammalian; Biomechanical Phenomena
PubMed: 38937030
DOI: 10.1016/bs.ctdb.2024.05.001 -
Journal of Neurovirology Jun 2024After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's...
After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.
PubMed: 38935226
DOI: 10.1007/s13365-024-01218-7 -
Frontiers in Endocrinology 2024The utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves... (Comparative Study)
Comparative Study
INTRODUCTION
The utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves safety by mitigating the risks associated with ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. There has been an increasing debate in recent years regarding the advisability of making elective frozen embryo transfer the standard practice. Our study aims to determine the optimal choice between fresh and frozen embryo transfer, as well as whether the transfer should occur at the cleavage or blastocyst stage.
METHOD
In this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, were analyzed. The study included 51,762 eligible female participants who underwent ART and embryo transfer. Pregnancy outcomes, maternal complications, and singleton neonatal outcomes were evaluated using the National Health Insurance Database from January 1st, 2013, to December 31st, 2018. Cases were categorized into groups based on whether they underwent fresh or frozen embryo transfers, with further subdivision into cleavage stage and blastocyst stage transfers. Exposure variables encompassed clinical pregnancy rate, live birth rate, OHSS, pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, preterm premature rupture of membranes (PPROM), gestational age, newborn body weight, and route of delivery.
RESULTS
Frozen blastocyst transfers showed higher rates of clinical pregnancy (CPR) and live births (LBR) compared to fresh blastocyst transfers. Conversely, frozen cleavage stage transfers demonstrated lower rates of clinical pregnancy and live birth compared to fresh cleavage stage transfers. Frozen embryo transfers were associated with reduced risks of OHSS but were linked to a higher risk of pregnancy-induced hypertension compared to fresh embryo transfers. Additionally, frozen embryo transfers were associated with a higher incidence of large for gestational age infants and a lower incidence of small for gestational age infants.
CONCLUSION
The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, FET is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option.
Topics: Humans; Female; Pregnancy; Embryo Transfer; Adult; Retrospective Studies; Cryopreservation; Pregnancy Outcome; Infant, Newborn; Taiwan; Pregnancy Rate; Cohort Studies; Fertilization in Vitro; Live Birth; Blastocyst
PubMed: 38933826
DOI: 10.3389/fendo.2024.1400255