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Data in Brief Aug 2024Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and...
Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and high-intensity ultraviolet radiation. Based on the unique physiological and morphological characteristics of the Tibetan people, they have outstanding hypoxia adaptation skills and can continue to thrive in plateau hypoxia. The placenta of high-altitude Tibetans is protected from oxidative stress during delivery; however, little is known about changes in placental protein expression during vaginal delivery. In this study, we aimed to reveal these adaptive mechanisms by studying changes in placental protein expression during vaginal delivery in high-altitude Tibetans, low-altitude Tibetans, and low-altitude Han populations. Studying the changing mechanisms of maternal responses to hypoxia at high altitudes can reveal the molecular mechanisms of maternal and fetal adaptation to hypoxia at high altitudes and provide theories for preventing and treating maternal hypoxia and intrauterine growth and development restriction caused by other diseases.
PubMed: 38948405
DOI: 10.1016/j.dib.2024.110542 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe...
Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-β2 glycoprotein Ⅰ domain Ⅰ antibody (aβ2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.
PubMed: 38948301
DOI: 10.12182/20240560104 -
Frontiers in Immunology 2024A maternal vaccine to protect newborns against invasive infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy...
A maternal vaccine to protect newborns against invasive infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.
PubMed: 38947337
DOI: 10.3389/fimmu.2024.1430901 -
MedRxiv : the Preprint Server For... Jun 2024Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We...
BACKGROUND
Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses.
METHODS
We analyzed data from 633 infants born to mothers enrolled in a randomized trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0-12 months of age. Using generalized linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrollment, maternal age, maternal parasitemia at enrollment, education, and wealth.
FINDINGS
SP increased LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased WLZ by 0.11-0.28 Z from 2-8 months compared to SP among infants of multigravidae. We did not observe these differences among primigravida. Mediators of SP included increased birth weight and length and maternal stem cell factor at delivery. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery.
INTERPRETATION
In high malaria transmission settings, different IPTp regimens influenced infant growth among multigravidae through distinct pathways in the period of exclusive breastfeeding, when few other interventions are available.
FUNDING
Stanford Center for Innovation and Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.
RESEARCH IN CONTEXT
Intermittent Preventive Treatment in Pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the WHO for regions with moderate-to-high malaria transmission. While SP is effective in reducing neonatal mortality and low birth weight, its efficacy has diminished in some areas of sub-Saharan Africa due to widespread parasite resistance to SP. Although IPTp with dihydroartemisinin-piperaquine (IPTp-DP) has demonstrated superior efficacy in reducing malaria in pregnancy, its impact on birth outcomes has not significantly surpassed that of SP. The ultimate goal of IPTp extends beyond enhancing birth outcomes to include benefits during infancy and later stages. Yet, the effects of SP vs. DP in relation to infant growth post-birth and the underlying mechanisms remain unknown. Prior studies also found that different IPTp regimens worked through different pathways, with DP influencing birth outcomes by reducing placental malaria and SP influencing them through non-malarial pathways such as maternal weight gain. Here, we re-analyzed data from of a randomized trial in Uganda to explore the impacts of these two IPTp regimens on infant growth and to understand potential mechanisms underlying its impacts on infant growth. This study quantified how IPTp with SP compared to DP influenced infants' growth trajectories, both ponderal and linear, during the first year of life. We found that SP improved linear growth of infants up to age 4 months compared to DP, and DP improved ponderal growth of infants from 2-8 months compared to SP among babies who were born to multigravidae. In addition, we identified birth size, placental malaria, and certain markers of maternal inflammation measured at delivery using the Olink Target 96 inflammation panel as pathways through which IPTp influenced infant growth. Our approach provides new insights into effects of IPTp beyond birth and the mechanisms by which IPTp impacts infant growth. Our study provides evidence that different IPTp regimens can influence infant postnatal growth through distinct pathways. Our findings highlight the potential of combined SP and DP IPTp regimens and bolster the evidence base for continued delivery of IPTp to improve maternal and child health outcomes, particularly in malaria-endemic regions.
PubMed: 38947035
DOI: 10.1101/2024.06.09.24308656 -
Frontiers in Cell and Developmental... 2024Embryo implantation involves a series of events that bring the embryo and maternal tissues into contact to support post-implantation development in mammals. During...
Embryo implantation involves a series of events that bring the embryo and maternal tissues into contact to support post-implantation development in mammals. During implantation, alignment of the embryonic-abembryonic (E-Ab) axis of the blastocyst with the mesometrial-antimesometrial (M-AM) axis of the uterus precedes post-implantation embryonic development and placentation. In the present study, we observed the morphological changes in blastocysts and the endometrial luminal epithelium (LE) that occur during the alignment of the embryonic and the uterine axes. We found that at the time that the blastocysts attached to the LE at the mural trophectoderm, the embryonic axis was not aligned with the uterine axis. Alignment of the embryonic E-Ab axis with the uterine M-AM axis occurred after E4.0, and the embryo was significantly elongated during the process. The depth of the implantation chamber (IC) correlated with the degree of alignment, suggesting that elongated embryos are oriented along the M-AM axis during IC formation. Transplantation of the Concanavalin A (Con A)-coated beads induced IC formation, and the alignment of two Con A-coated beads present in the same IC in the M-AM direction suggested that elongated materials can align along the M-AM axis. These data suggest that an elongated shape of the embryo and IC formation coordinate the alignment of the embryonic and uterine axes.
PubMed: 38946796
DOI: 10.3389/fcell.2024.1421222 -
Nature Ecology & Evolution Jul 2024Ninu (greater bilby, Macrotis lagotis) are desert-dwelling, culturally and ecologically important marsupials. In collaboration with Indigenous rangers and conservation...
Ninu (greater bilby, Macrotis lagotis) are desert-dwelling, culturally and ecologically important marsupials. In collaboration with Indigenous rangers and conservation managers, we generated the Ninu chromosome-level genome assembly (3.66 Gbp) and genome sequences for the extinct Yallara (lesser bilby, Macrotis leucura). We developed and tested a scat single-nucleotide polymorphism panel to inform current and future conservation actions, undertake ecological assessments and improve our understanding of Ninu genetic diversity in managed and wild populations. We also assessed the beneficial impact of translocations in the metapopulation (N = 363 Ninu). Resequenced genomes (temperate Ninu, 6; semi-arid Ninu, 6; and Yallara, 4) revealed two major population crashes during global cooling events for both species and differences in Ninu genes involved in anatomical and metabolic pathways. Despite their 45-year captive history, Ninu have fewer long runs of homozygosity than other larger mammals, which may be attributable to their boom-bust life history. Here we investigated the unique Ninu biology using 12 tissue transcriptomes revealing expression of all 115 conserved eutherian chorioallantoic placentation genes in the uterus, an XYY sex chromosome system and olfactory receptor gene expansions. Together, we demonstrate the holistic value of genomics in improving key conservation actions, understanding unique biological traits and developing tools for Indigenous rangers to monitor remote wild populations.
PubMed: 38945974
DOI: 10.1038/s41559-024-02436-2 -
The Journal of Reproduction and... Jun 2024Retained placenta (RP) adversely affects postpartum productivity and reproduction in dairy cattle. Thus, methods to predict the occurrence of RP before calving would be...
Retained placenta (RP) adversely affects postpartum productivity and reproduction in dairy cattle. Thus, methods to predict the occurrence of RP before calving would be desirable. Herein, we assessed whether vaginal temperature measurements (which have already been applied to detect calving) could be used to predict the occurrence of RP in cattle. A vaginal temperature recording device was inserted into the vagina of 49 pregnant Holstein-Friesian heifers (n = 16) and cows (n = 33); this device recorded the vaginal temperature every 5 min until the device dropped out at calving. Serum was collected 10 days before the expected calving date. The time points of calving and placental expulsion were identified via video recordings. We further calculated calving duration (temperature decrease to calving) and placenta expulsion time (PE time = calving to placenta expulsion). The PE times were divided into four categories (0-4 h, 4-8 h, 8-12 h, and RP at >12 h), while subsequent analysis revealed that an extension of the PE time dependent on the shortening of the calving duration (P < 0.05). The vaginal temperature patterns also differed in a PE time-dependent manner, and cows with RP did not show any re-elevation of vaginal temperature. Serum analyses indicated an energy deficiency in RP cattle. These results suggest that RP may be detected early as a specific change in the vaginal temperature associated with reproductive hormone secretion.
PubMed: 38945853
DOI: 10.1262/jrd.2024-012 -
Biological & Pharmaceutical Bulletin 2024Porcine placental extract (PPE) is commonly used in various health foods and cosmetics. PPE use in cosmetics predominantly consist of the water-soluble fraction derived...
Porcine placental extract (PPE) is commonly used in various health foods and cosmetics. PPE use in cosmetics predominantly consist of the water-soluble fraction derived from the entire placenta. In this report, we examined the effect of the hydrophobic constituents of the PPE, specifically the sphingolipid-enriched fraction designated as the sphingolipid-enriched porcine placental extract (SLPPE), on the expression of genes associated with skin function in cultured normal human epidermal keratinocytes. Using quantitative RT-PCR (qRT-PCR) analysis, we found that SLPPE concentrations ranging from 25 to 100 µg/mL upregulated the gene expression of key components associated with the cornified envelope structure (filaggrin (FLG), involucrin (IVL) and loricrin (LOR)), cornification enzymes (transglutaminase 1 (TGM1) and TGM5) and the desquamation enzymes (kallikrein 5 (KLK5) and KLK7). Additionally, KLK5p and FLG protein (FLGp) were detected in the culture supernatants of keratinocytes treated with SLPPE at these concentrations. These findings suggest that SLPPE is possible to promote the cornification and desquamation in epidermal keratinocytes, and it may offer potential benefits in cosmetics.
Topics: Keratinocytes; Humans; Filaggrin Proteins; Animals; Transglutaminases; Swine; Sphingolipids; Kallikreins; Placental Extracts; Cells, Cultured; Female; Intermediate Filament Proteins; Membrane Proteins; Protein Precursors; Pregnancy
PubMed: 38945844
DOI: 10.1248/bpb.b24-00109 -
The Journal of Maternal-fetal &... Dec 2024The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the...
BACKGROUND
The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the dehiscent area, eliminates associated intraluminal fibrosis, and establishes a vascularized anterior wall by creating a sliding myometrial flap.
OBJECTIVE
Propose a comprehensive surgical repair for recurrent and large low hysterotomy defects in women seeking pregnancy or recurrent spotting.
STUDY DESIGN
A retrospective cohort analysis included 54 patients aged 25-41 with recurrent large cesarean scar defects treated at Otamendi, CEMIC, and Valle de Lili hospitals. Comprehensive surgical repair was performed by suprapubic laparotomy, involving a wide opening of the vesicouterine space, removal of the dehiscent cesarean scar and all intrauterine abnormal fibrous tissues, using a glide myometrial flap, and intramyometrial injection of autologous platelet-rich plasma. Qualitative variables were determined, and descriptive statistics were employed to analyze the data in absolute frequencies or percentages. The data obtained were processed using the Infostat statistic program.
RESULTS
Following the repair, all women experienced normal menstrual cycles and demonstrated an adequate lower uterine segment thickness, with no evidence of healing defects. All patients experienced early ambulation and were discharged within 24 h. Uterine hemostasis was achieved at specific points, minimizing the use of electrocautery. The standard duration of the procedure was 60 min (skin-to-skin), and the average bleeding was 80-100 ml. No perioperative complications were recorded. A control T2-weighted MRI was performed six months after surgery. All patients displayed a clean, unobstructed endometrial cavity with a thick anterior wall (Median: 14.98 mm, IQR 13-17). Twelve patients became pregnant again, all delivered by cesarean between 36.1 and 38.0 weeks, with a mean of 37.17 weeks. The thickness of the uterine segment before cesarean ranged between 3 and 7 mm, with a mean of 3.91 mm. No cases of placenta previa, dehiscence, placenta accreta spectrum (PAS), or postpartum hemorrhage were reported.
CONCLUSIONS
The comprehensive repair of recurrent low-large defects offers a holistic solution for addressing recurrent hysterotomy defects. Innovative repair concepts effectively address the wound defect and associated fibrosis, ensuring an appropriate myometrial thickness through a gliding myometrial flap.
Topics: Humans; Female; Adult; Retrospective Studies; Hysterotomy; Pregnancy; Cicatrix; Surgical Flaps; Cesarean Section; Myometrium; Recurrence
PubMed: 38945839
DOI: 10.1080/14767058.2024.2365344 -
Placenta Jun 2024This study aimed to explore the association between ferroptosis, a newly identified type of cell death, and the role of retinoic acid in developing pregnancy...
INTRODUCTION
This study aimed to explore the association between ferroptosis, a newly identified type of cell death, and the role of retinoic acid in developing pregnancy complications. Therefore, the effects of all-trans retinoic acid (ATRA) on ferroptosis susceptibility in BeWo cells were assessed to understand abnormal placental development.
METHODS
BeWo cells were used as surrogates for cytotrophoblasts. The effect of ATRA on ferroptosis sensitivity was assessed on BeWo cells pretreated with ATRA or dimethyl sulfoxide (DMSO; control), following which the LDH-releasing assay was performed. The effects of ATRA pretreatment on the antioxidant defense system (including glutathione [GSH], mitochondrial membrane potential, and heme oxygenase-1 [HMOX1]) in BeWo cells were assessed using assay kits, RT-qPCR, and HMOX1 immunostaining. To evaluate the effect of ATRA on BeWo cells, HMOX1 was silenced in BeWo cells using shRNA.
RESULTS
ATRA pretreatment increased ferroptosis resistance in BeWo cells. Although with pretreatment, qPCR indicated upregulation of HMOX1, no significant change was observed in the GSH levels or mitochondrial membrane potential. This was corroborated by intensified immunostaining for heme oxygenase-1 protein (HO-1). Notably, the protective effect of ATRA against ferroptosis was negated when HO-1 was inhibited. Although HMOX1-silenced BeWo cells exhibited heightened ferroptosis sensitivity compared with controls, ATRA pretreatment counteracted ferroptosis in these cells.
DISCUSSION
ATRA pretreatment promotes BeWo cell viability by suppressing ferroptosis and upregulating HMOX1 and this can be used as a potential therapeutic strategy for addressing placental complications associated with ferroptosis.
PubMed: 38945098
DOI: 10.1016/j.placenta.2024.06.012