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Background: This study aims to conduct a preliminary exploration of the correlation between the oral microbiota of full-term pregnant women and both local placental immunity and the systemic immune system of the mother., Methods: A total of 26 pregnant women participated in this study, with samples collected from oral swabs, placental tissue, and peripheral venous blood. High-throughput sequencing was used to examine the oral microbial community. Flow cytometry was employed to assess immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid bead chip technology were utilized to detect cytokines in both placental tissue and peripheral venous blood., Results: In placental tissue, The oral microbial community is primarily negatively correlated with placental CD3+CD4+CD8+T cells and positively correlated with placental IL-5. In the peripheral blood, The oral microbial community is primarily positively correlated with maternal systemic immune parameters, including CD3+CD4+ T cells and the CD4+/CD8+ ratio, as well as positively correlated with peripheral IL-18., Conclusions: The oral microbiota of full-term pregnant women participates in the regulatory function of the maternal immune system. Meanwhile, the oral microbial community may also be an important factor mediating local immune regulation in the placenta., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nocardioform placentitis is a poorly understood disease of equine late gestation. The presence of nocardioform, filamentous branching gram-positive bacteria, has been linked to the disease, with Crossiella equi, Amycolatopsis spp., and Streptomyces spp. being the most frequently identified bacteria. However, these bacteria are not found in all clinical cases in addition to being isolated from healthy, normal postpartum placentas. To better understand this form of placentitis, we analyzed the microbial composition in the equine placenta (chorioallantois) of both healthy postpartum (control; n = 11) and nocardioform-affected samples (n = 22) using 16S rDNA sequencing. We found a lower Shannon index in nocardioform samples, a higher Chao1 index in nocardioform samples, and a difference in beta diversity between control and nocardioform samples (p < 0.05), suggesting the presence of dysbiosis during the disease. In the majority of the NP samples (77 %), one of the following genera-Amycolatopsis, Crossiella, Lentzea, an unidentified member of the Pseudonocardiaceae family, Mycobacterium, or Enterococcus -represented over 70 % of the relative abundance. Overall, the data suggest that a broader spectrum of potential opportunistic pathogens could be involved in nocardioform placentitis, extending beyond the traditionally recognized bacteria, resulting in a similar histomorphological profile., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The reproductive features of equine leptospirosis are often neglected. Equine genital leptospirosis is characterized as a silent chronic syndrome, and besides abortions, leads to placental abnormalities, stillbirths, and birth of weak foals. This study aimed to study the occurrence of placental abnormalities associated with Leptospira interrogans infection in naturally infected mares under field conditions. The studied herd had a high occurrence of placentitis and abortions. Ten pregnant mares, eight with placental abnormalities on ultrasonography and were selected. Serum and cervicovaginal mucus (CVM) samples were collected for serology and PCR, respectively. Positive samples in lipL32-PCR were submitted to the sequencing of the secY gene. In lipL32-PCR of CVM, five out of 10 (50%) mares were positive and all were characterized as Leptospira interrogans. Our results highlight the presence of placental abnormalities in the reproductive subclinical leptospirosis syndrome. We encourage field veterinarians to include leptospirosis testing in their reproductive management., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Meconium-stained amniotic fluid (MSAF) often signifies colonization of the amniotic sac by microorganisms. This study investigated additional adverse obstetric outcomes associated with MSAF in deliveries complicated by maternal intrapartum fever (IF)., Methods: This retrospective study included all singleton pregnancies from 2014 to 2020, with intrapartum maternal fever ≥ 38 °C during a trial of labor. In accordance with departmental protocol, all patients received intravenous antibiotic therapy consisting of ampicillin and gentamicin in the absence of allergies to these medications. Subsequent antibiotic therapy was adjusted based on the culture results. Antibiotic treatment was discontinued postpartum after 48 h without fever. Swab cultures were obtained immediately postpartum from both the maternal and fetal sides of the placenta. Maternal and fetal outcomes, along with positive placental cultures, were compared between participants with MSAF&IF and those with clear amniotic fluid &IF (control group)., Results: In comparison to the control group (n = 1089), the MSAF&IF group (n = 264) exhibited significantly higher rates of cesarean delivery (CD) (p = 0.001), CD due to non-reassuring fetal heart rate (p = 0.001), and cord pH ≤ 7.1 (p = 0.004). Positive swab cultures from the placental maternal and fetal sides were more prevalent among the MSAF&IF group (23.1% vs. 17.6%, p = 0.041 and 29.2% vs. 22.9%, p = 0.032, respectively). Placental cultures yielding gastrointestinal pathogens and extended spectrum beta-lactamase were notably more common in the MSAF&IF group compared to controls (p = 0.023). However, there was no significant difference between groups regarding the rate of group B streptococcus positive placental cultures., Conclusions: Women experiencing IF and MSAF during labor face an elevated risk of CD compared to those with IF alone. The presence of MSAF heightens the risk of positive placental cultures, particularly with gastrointestinal and extended spectrum beta-lactamase pathogens., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pregnancy is extremely vulnerable to external environmental influences. Bisphenol A, an endocrine-disrupting chemical, poses a significant environmental hazard to individuals of all ages and stages, particularly during pregnancy. The placenta is a temporary organ facilitating the connection between the mother and fetus. While it can detoxify certain exogenous substances, it is also vulnerable to the impacts of endocrine disruptors. Likewise, the intestinal flora is highly sensitive to exogenous stresses and environmental pollutants. The regulation of gut microbiota plays a crucial role in ensuring the health of both the mother and the fetus. The gut-placental axis connects the gut, gut microbes, placenta, and fetus. Exploring possible effects on placental function and fetal development involves analyzing changes in gut microbiota composition. Given that bisphenol A may cross the intestine and affect intestinal function, gut microorganisms, and their metabolites, as well as its potential impact on the placenta, resulting in impaired placental function and fetal development, this study aims to establish a link between bisphenol A exposure, intestinal microorganisms, placental function, and fetal development. This paper seeks to analyze the effects of maternal exposure to bisphenol A during pregnancy on the balance of the maternal gut microbiota, placental function, and fetal development, considering the key role of the gut-placental axis. Additionally, this paper proposes potential directions for future research emphasizing the importance of mitigating the adverse outcomes of bisphenol A exposure during pregnancy in both human and animal studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanisms and challenges in replicating trophoblast-pathogen interactions using in vitro models, we tested an existing stem-cell-derived model of trophoblast development for its relevance to infection with Toxoplasma gondii . We grew human trophoblast stem cells (TS CT ) under conditions leading to either syncytiotrophoblast (TS SYN ) or cytotrophoblast (TS CYT ) and infected them with T. gondii . We evaluated T. gondii proliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TS SYNs cells showed similar ultrastructure compared to primary cells and villous explants when analyzed by transmission electron microscopy and scanning electron microscopy (SEM), a resistance to T. gondii adhesion could be visualized on the SEM level. Furthermore, TS SYNs were highly refractory to parasite adhesion and replication, while TS CYTs were not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded to T. gondii infection. We also evaluated if TS SC -derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen, Listeria monocytogenes . We demonstrate that TS SYNs are highly resistant to L. monocytogenes , while TS CYTs are not. Like T. gondii , TS SYN resistance to L. monocytogenes was at the level of bacterial adhesion. Altogether, our data indicate that stem-cell-derived trophoblasts recapitulate resistance profiles of primary cells to T. gondii and highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.IMPORTANCECongenital toxoplasmosis can cause a devastating consequence to the fetus. To reach the fetus's tissues, Toxoplasma gondii must cross the placenta barrier. However, how this parasite crosses the placenta and the precise molecular mechanisms of placental resistance to this parasite are still unknown. In this study, we aimed to characterize a new cellular model of human trophoblast stem cells to determine their resistance, susceptibility, and response to T. gondii . Syncytiotrophoblast derived from trophoblast stem cells recapitulate the resistance profile similarly to placenta cells. We also showed that these cells are highly resistant to Listeria monocytogenes , at the level of bacterial adhesion. Our results suggest that resisting pathogen adhesion/attachment may be a generalized mechanism of syncytiotrophoblast resistance, and trophoblast stem cells represent a promising model to investigate cell-intrinsic mechanisms of resistance to pathogen adhesion and replication., Competing Interests: The authors declare no conflict of interest.

One of the main causes of human brucellosis is Brucella melitensis infecting small ruminants. To date, Rev1 is the only vaccine successfully used to control ovine and caprine brucellosis. However, it is pathogenic for pregnant animals, resulting in abortions and vaginal and milk shedding, as well as being infectious for humans. Therefore, there is an urgent need to develop an effective vaccine that is safer than Rev1. In efforts to further attenuate Rev1, we recently used wzm inactivation to generate a rough mutant (Rev1Δwzm) that retains a complete antigenic O-polysaccharide in the bacterial cytoplasm. The aim of the present study was to evaluate the placental pathogenicity of Rev1Δwzm in trophoblastic cells, throughout pregnancy in mice, and in ewes inoculated in different trimesters of pregnancy. This mutant was evaluated in comparison with the homologous 16MΔwzm derived from a virulent strain of B. melitensis and the naturally rough sheep pathogen B. ovis. Our results show that both wzm mutants triggered reduced cytotoxic, pro-apoptotic, and pro-inflammatory signaling in Bewo trophoblasts, as well as reduced relative expression of apoptosis genes. In mice, both wzm mutants produced infection but were rapidly cleared from the placenta, in which only Rev1Δwzm induced a low relative expression of pro-apoptotic and pro-inflammatory genes. In the 66 inoculated ewes, Rev1Δwzm was safe and immunogenic, displaying a transient serological interference in standard RBT but not CFT S-LPS tests; this serological response was minimized by conjunctival administration. In conclusion, these results support that B. melitensis Rev1Δwzm is a promising vaccine candidate for use in pregnant ewes and its efficacy against B. melitensis and B. ovis infections in sheep warrants further study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rev1Δwzm is protected under a CSIC-UPNA patent WO/2019/101993 (PCT/EP2018/082539) and both are public institutions without any conflict of interests with this publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth., Methods: The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed., Results: The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of Chlamydia trachomatis , Neisseria gonorrhea, Listeria monocytogenes, and Mycoplasma genitalium infections was zero in both groups. The highest prevalence of Gardnerella vaginalis was 19 (19%) in the case group and Ureaplasma parvum 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between Gardnerella vaginalis bacteria and spontaneous preterm delivery., Conclusion: The results of our study showed that except for Gardnerella vaginalis bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ahmadi, Khadem Erfan, Roshani, Derakhshan, Ramazanzadeh, Farhadifar, Mohsenpour, Shahgheibi, Zarei, Salimizand and Nikkhoo.)

Objective: The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model., Methods: Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing., Results: Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed., Conclusion: Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth., (© 2024. The Author(s).)

This review illuminates the complex interplay between various maternal microbiomes and their influence on preterm birth (PTB), a driving and persistent contributor to neonatal morbidity and mortality. Here, we examine the dynamics of oral, gastrointestinal (gut), placental, and vaginal microbiomes, dissecting their roles in the pathogenesis of PTB. Importantly, focusing on the vaginal microbiome and PTB, the review highlights (1) a protective role of Lactobacillus species; (2) an increased risk with select anaerobes; and (3) the influence of social health determinants on the composition of vaginal microbial communities., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to and even cross the placenta, causing pregnancy complications with potential lifelong impacts on the child's health. Here, we profiled at the single-cell level the placental responses to three pathogens associated with intrauterine complications-Plasmodium falciparum, Listeria monocytogenes, and Toxoplasma gondii. We found that upon exposure to the pathogens, all placental lineages trigger inflammatory responses that may compromise placental function. Additionally, we characterized the responses of fetal macrophages known as Hofbauer cells (HBCs) to each pathogen and propose that they are the probable niche for T. gondii. Finally, we revealed how P. falciparum adapts to the placental microenvironment by modulating protein export into the host erythrocyte and nutrient uptake pathways. Altogether, we have defined the cellular networks and signaling pathways mediating acute placental inflammatory responses that could contribute to pregnancy complications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully understood, leading to limited effective treatments. The goal of this study is to enhance our knowledge of its causes, devise prevention strategies, and develop treatments., Methods: We performed a systematic literature search. Six models regarding the pathogenesis of preeclampsia are discussed in this review., Results: This review focuses on the latest advancements in understanding preeclampsia's origins. Preeclampsia is a complex condition caused by various factors, processes, and pathways. Reduced blood flow and oxygen to the uterus and placenta, heightened inflammatory reactions, immune imbalances, altered genetic changes, imbalanced blood vessel growth factors, and disrupted gut bacteria may contribute to its development., Conclusion: Preeclampsia is thought to result from the interplay of these factors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR., Methods: In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient., Results: The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides , Akkermansia , Eubacterium&#95;coprostanoligenes&#95;group , Phascolarctobacterium , Parasutterella , Odoribacter , Lachnospiraceae&#95;UCG&#95;010 , and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota ( Tyzzerella ), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR., Conclusion: Metabolites (METHIONINE, alanine) as well as microbiota ( Tyzzerella ) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Hui Tang et al.)

Background: Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract METHODS: Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1-10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota., Results: We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70-82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation., Conclusions: Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease., (© 2024. The Author(s).)

Bacteria derived from the maternal circulation have been suggested to seed the human placenta during pregnancy leading to development of an intrinsic placental microbiome; however, other data indicates these bacteria are artifactual contaminants. Limited research on the localization of bacteria in human placental tissue is available, which may help differentiate resident placental bacteria from contaminants. This study spatially localizes bacteria in situ in normal late first to early second trimester human placenta by 16S rRNA chromogenic in situ hybridization and demonstrates patterns consistent with both contaminants and intraparenchymal signals. These results suggest that placental microbiome studies may benefit from spatial strategies that can exclude surface contamination., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The microbiome -defined as the microbiota (bacteria, archaea, lower and higher eukaryotes), their genomes, and the surrounding environmental conditions- has a well-described range of physiological functions. Thus, an imbalance of the microbiota composition -dysbiosis- has been associated with pregnancy complications or adverse fetal outcomes. Although there is controversy about the existence or absence of a microbiome in the placenta and fetus during healthy pregnancy, it is known that gut microbiota can produce bioactive metabolites that can enter the maternal circulation and may be actively or passively transferred through the placenta. Furthermore, the evidence suggests that such metabolites have some effect on the fetus. Since the microbiome can influence the epigenome, and modifications of the epigenome could be responsible for fetal programming, it can be experimentally supported that the maternal microbiome and its metabolites could be involved in fetal programming. The developmental origin of health and disease (DOHaD) approach looks to understand how exposure to environmental factors during periods of high plasticity in the early stages of life (e.g., gestational period) influences the program for disease risk in the progeny. Therefore, according to the DOHaD approach, the influence of maternal microbiota in disease development must be explored. Here, we described some of the diseases of adulthood that could be related to alterations in the maternal microbiota. In summary, this review aims to highlight the influence of maternal microbiota on both fetal development and postnatal life, suggesting that dysbiosis on this microbiota could be related to adulthood morbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruiz-Triviño, Álvarez, Cadavid J. and Alvarez.)

Background: Anaplasma phagocytophilum is a tick-borne zoonotic bacterium that is the aetiologic pathogen of tick-borne fever (TBF) in ruminants. In clinical bovine cases of TBF, abortion and stillbirth may be observed. However, in this regard, the pathophysiology of TBF has not yet been completely elucidated, and no clear guidelines to diagnose A. phagocytophilum-related abortions and perinatal mortalities (APM) are available., Methods: This exploratory study aimed to investigate the presence of A. phagocytophilum in bovine cases of APM and determine whether placental or fetal spleen tissue has the greatest sensitivity for A. phagocytophilum identification. The placenta and fetal spleen of 150 late-term bovine APM cases were analysed using real-time PCR to detect A. phagocytophilum., Results: A total of 2.7% of sampled placentas were positive for A. phagocytophilum, while none of the fetal spleen samples was., Limitations: No histopathology to detect associated lesions was performed. Consequently, no evidence of causality between the detection of A. phagocytophilum and APM events could be achieved., Conclusion: The detection of A. phagocytophilum suggests a potential role of this pathogen in bovine APM, and placental tissue seems to be the most suitable tissue for its identification., (© 2023 British Veterinary Association.)

In spite of controversy, recent studies present evidence that a microbiome is present in the human placenta. However, there is limited information about a potential equine placental microbiome. In the present study, we characterized the microbial population in the equine placenta (chorioallantois) of healthy prepartum (280 days of gestation, n = 6) and postpartum (immediately after foaling, 351 days of gestation, n = 11) mares, using 16S rDNA sequencing (rDNA-seq). In both groups, the majority of bacteria belonged to the phyla Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidota. The five most abundant genera were Bradyrhizobium, an unclassified Pseudonocardiaceae, Acinetobacter, Pantoea, and an unclassified Microbacteriaceae. Alpha diversity (p < 0.05) and beta diversity (p < 0.01) were significantly different between pre- and postpartum samples. Additionally, the abundance of 7 phyla and 55 genera was significantly different between pre- and postpartum samples. These differences suggest an effect of the caudal reproductive tract microbiome on the postpartum placental microbial DNA composition, since the passage of the placenta through the cervix and vagina during normal parturition had a significant influence on the composition of the bacteria found in the placenta when using 16S rDNA-seq. These data support the hypothesis that bacterial DNA is present in healthy equine placentas and opens the possibility for further exploration of the impact of the placental microbiome on fetal development and pregnancy outcome., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other journal., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A variety of infectious agents including viral, bacterial, and fungal organisms can cause equine abortion and placentitis. Knowledge of normal anatomy and the common pattern distribution of different infectious agents will assist the practitioner in evaluating the fetus and/or placenta, collecting appropriate samples for further testing, and in some cases, forming a presumptive diagnosis. In all cases, it is recommended to confirm the diagnosis with molecular, serologic, or microbiological testing. If a causative agent can be identified, then appropriate biosecurity and vaccination measures can be instituted on the farm., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA or delivery-associated contamination. Using fifteen publicly available 16S rRNA gene datasets, existing data were uniformly re-analyzed with DADA2 to maximize comparability. While Amplicon Sequence Variants (ASVs) identified as Lactobacillus, a typical vaginal bacterium, were highly abundant and prevalent across studies, this prevalence disappeared after applying likely  DNA contaminant removal to placentas from term cesarean deliveries. A six-study sub-analysis targeting the 16S rRNA gene V4 hypervariable region demonstrated that bacterial profiles of placental samples and technical controls share principal bacterial ASVs and that placental samples clustered primarily by study origin and mode of delivery. Contemporary DNA-based evidence does not support the existence of a placental microbiota.ImportanceEarly-gestational microbial influences on human development are unclear. By applying DNA sequencing technologies to placental tissue, bacterial DNA signals were observed, leading some to conclude that a live bacterial placental microbiome exists in typical term pregnancy. However, the low-biomass nature of the proposed microbiome and high sensitivity of current DNA sequencing technologies indicate that the signal may alternatively derive from environmental or delivery-associated bacterial DNA contamination. Here we address these alternatives with a re-analysis of 16S rRNA gene sequencing data from 15 publicly available placental datasets. After identical DADA2 pipeline processing of the raw data, subanalyses were performed to control for mode of delivery and environmental DNA contamination. Both environment and mode of delivery profoundly influenced the bacterial DNA signal from term-delivered placentas. Aside from these contamination-associated signals, consistency was lacking across studies. Thus, placentas delivered at term are unlikely to be the original source of observed bacterial DNA signals., (© 2023. The Author(s).)

Aim: To investigate microbial profiles in placentas from a population of East African mothers with and without adverse pregnancy outcomes and with regard to their periodontal status., Material and Methods: Thirty-six placentas from pregnant women from Tanzania were classified into three groups according to both pregnancy outcome and the mother's periodontal health. The microbial composition in each group was then compared using 16S rRNA metagenomics. Additionally, placenta specimens were analyzed histologically for chorioamnionitis by a single pathologist blinded to the clinical data., Results: The greatest differences were observed in the group of mothers with periodontitis. The microbial load was low in all three groups of mothers. Periodontitis had a notable influence on the structure of the placental microbiota. Three phyla and 44 genera were associated with periodontitis, whereas only the Tenericutes phylum was associated with the adverse pregnancy variable. Streptococcaceae and Mycoplasmataceae families were associated with both periodontitis and adverse pregnancy outcomes. Finally, although the differences for chorioamnionitis were not significant, this intra-amniotic infection was more frequent in the placentas from mothers with periodontitis., Conclusions: Our findings suggest that bacteria from the oral cavity may involve the feto-placental unit, and that periodontitis may be a modulating factor of the microbial community present in this niche., (© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Abortions in domestic ruminants cause significant economic losses to farmers. Determining the cause of an abortion is important for control efforts, but it can be challenging. All available diagnostic methods in the bacteriology laboratory should be employed in every case due to the many limiting factors (autolysis, lack of history, range of samples) that complicate the investigation process. The purpose of this study was to determine whether the recovery of diagnostically significant isolates from domestic ruminant abortion cases could be increased through the use of a combination of the existing aerobic culture and Brucella selective method with methods that are commonly recommended in the literature reporting abortion investigations. These methods are examination of wet preparations and impression smears stained by the modified Ziehl-Neelsen method, anaerobic, microaerophilic, Leptospira, Mycoplasma and fungal culture. Samples of placenta and aborted foetuses from 135 routine clinical abortion cases of cattle (n = 88), sheep (n = 25) and goats (n = 22) were analysed by the new combination of methods. In 46 cases, bacteria were identified as aetiological agents and in one case a fungus. Isolation of Brucella species increased to 7.4% over two years compared with the previous 10 years (7.3%), as well as Campylobacter jejuni (n = 2) and Rhizopus species (n = 1). Salmonella species (5.9%) and Trueperella pyogenes (4.4%) were also isolated more often. In conclusion, the approach was effective in removing test selection bias in the bacteriology laboratory. The importance of performing an in-depth study on the products of abortion by means of an extensive, combination of conventional culture methods was emphasised by increased isolation of Brucella abortus and isolation of C. jejuni. The combination of methods that yielded the most clinically relevant isolates was aerobic, microaerophilic, Brucella and fungal cultures.

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts., (© 2023. Springer Nature Limited.)

Opportunistic bacteria and fungi are commonly reported causes of bovine abortion in a small percentage of fetal losses of infectious etiology in cattle. The objective of this study was to characterize the pathological and etiological findings in fetuses aborted due to secondary bacterial and fungal infections submitted for postmortem examination between 2004 and 2019 in the State of Rio Grande do Sul, Brazil. Nineteen cases of bacterial etiology and five cases of fungal etiology were assessed. In cases of bacterial etiology, gross changes were uncommon and two different microscopic patterns were observed: (1) primary bronchopneumonia with occasional dissemination in cases of Staphylococcus sp., Streptococcus sp., and Mannheimia haemolytica infections; and (2) systemic disease with sepsis in cases of Escherichia coli and Listeria sp. infections. Aspergillus sp. was the main fungal agent identified, and cases of mycotic abortion were characterized by placentitis, dermatitis, and pneumonia. Fetal membranes were available for examination in less than half of the submissions (11/24), and placental lesions were observed in all cases. This study reaffirms the importance of postmortem examinations in the determination of causes of fetal loss in cattle and highlights pathological findings commonly observed in fetuses aborted due to sporadic bacterial and fungal agents., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Placental immunity is critical for fetal health during pregnancy, as invading pathogens spread from the parental blood to the fetus through this organ. However, inflammatory responses in the placenta can adversely affect both the fetus and the pregnant person, and the balance between protective placental immune response and detrimental inflammation is poorly understood. Extracellular vesicles (EVs) are membrane-enclosed vesicles that play a critical role in placental immunity. EVs produced by placental trophoblasts mediate immune tolerance to the fetus and to the placenta itself, but these EVs can also activate detrimental inflammatory responses. The regulation of these effects is not well characterized, and the role of trophoblast EVs (tEVs) in the response to infection has yet to be defined. The Gram-positive bacterial pathogen Listeria monocytogenes infects the placenta, serving as a model to study tEV function in this context. We investigated the effect of L. monocytogenes infection on the production and function of tEVs, using a trophoblast stem cell (TSC) model. We found that tEVs from infected TSCs can induce the production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in recipient cells. Surprisingly, this tEV treatment could confer increased susceptibility to subsequent L. monocytogenes infection, which has not been reported previously as an effect of EVs. Proteomic analysis and RNA sequencing revealed that tEVs from infected TSCs had altered cargo compared with those from uninfected TSCs. However, no L. monocytogenes proteins were detected in tEVs from infected TSCs. Together, these results suggest an immunomodulatory role for tEVs during prenatal infection.

The microbiome is believed to be established during the birthing process through exposure to the maternal microbiome and immediate external environment. The absence of a microbiome prior to birth is based on the sterile womb hypothesis, which was formulated at the beginning of the 20th century and is supported primarily by the culture-based approach in microbiological studies.Findings of bacterial presence in products of fertilization such as the placenta, amniotic fluid, foetal membranes, and umbilical cord blood in studies using next-generation DNA sequencing technologies began to challenge the sterile nature of the intrauterine environment during gestation. These studies have been mainly criticized by their approach to contamination and inconclusive evidence of viability. The implications of bacterial presence in utero are far reaching in medicine and basic sciences. If commensal bacteria exist in the foetus, antibiotic therapies in pregnancy particularly for asymptomatic cases will need to be re-evaluated. Experimental studies utilizing gnotobiology may also be impacted by a realignment of theory.This review of existing literature aims to provide insight into the existence of bacteria in utero , specifically the foetal microbiome through analysis of experimental evidence and theoretical concepts, and to suggest approaches that may further provide clarity into this inquiry.

Preterm birth (PTB) poses great risk to neonatal health in Pakistan with few tertiary health care facilities. Role of intrauterine microbiome in maintaining healthy pregnancy has been highlighted. However, there is ongoing debate whether a true placental microbiome exist. We analyzed placental and vaginal microbiome through V3-V4 16srRNA sequencing and observed increased abundance of proteobacteria, with concomitant decline in the firmicutes population in preterm vagina. Simplistic placental microflora included many environmental microbes with PTB placenta carrying pathogenic microbes like ureaplasma and mycoplasma species. We observed contribution of environmental, vaginal and skin contamination in term versus pathobiome signatures in preterm placenta., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Group B Streptococcus (GBS) is one of the most common bacteria isolated in human chorioamnionitis. Placental infection due to GBS is a major risk factor for fetal organ injuries, preterm birth, perinatal morbidity and mortality, and life-long multiorgan morbidities. Preclinical and clinical studies have shown that GBS-induced infection drives polymorphonuclear (PMN) cell infiltration within the placenta, the hallmark of human chorioamnionitis. In preclinical and clinical studies, the upregulation of interleukin(IL)-1β in the placenta and maternal/fetal blood was associated with a high risk of neurodevelopmental impairments in the progeny. We hypothesized that targeted IL-1 blockade administered to the dam alleviates GBS-induced chorioamnionitis and the downstream fetal inflammatory response syndrome (FIRS). IL-1 receptor antagonist (IL-1Ra) improved the gestational weight gain of GBS-infected dams and did not worsen the infectious manifestations. IL-1Ra reduced the IL-1β titer in the maternal sera of GBS-infected dams. IL-1Ra decreased the levels of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), and polymorphonuclear (PMN) infiltration in GBS-infected placenta. IL-1Ra treatment reduced the IL-1β titer in the fetal sera of GBS-exposed fetuses. IL-1 blockade also alleviated GBS-induced FIRS and subsequent neurobehavioral impairments of the offspring without worsening the outcome of GBS infection. Altogether, these results showed that IL-1 plays a key role in the physiopathology of live GBS-induced chorioamnionitis and consequent neurobehavioral impairments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ayash, Vancolen, Segura, Allard and Sebire.)

Objective: The purpose of this study was to identify the most common causes of equine abortion in Canada, and to compare findings to similar reports from other countries., Animal: Equine., Procedure: Necropsy reports from 901 equine abortion cases were acquired from provincial veterinary diagnostic laboratories across Canada. The final diagnosis was classified into basic abortion causes (infectious, non-infectious, unknown) and into primary and secondary categories for analysis., Results: Non-infectious causes of abortion were the most frequently identified in Canada, with fetoplacental causes, including umbilical cord torsion or placental insufficiency, being the most common primary diagnosis category. Streptococcus and Escherichia were the bacterial species most often identified as causing infectious abortions, whereas equine herpesvirus-1 was implicated in all viral abortions identified., Conclusion: The high rate of non-infectious causes of abortion was similar to previous studies conducted in the United Kingdom. This finding was somewhat dissimilar to the USA, which had higher rates of infectious abortions, despite Canada's geographic proximity to the USA. The reason for variations among countries in equine abortion causes is unknown., Clinical Relevance: The large number of fetoplacental-related abortions identified in this study emphasized the need for submission of both the fetus and placenta, if possible, to increase the probability of a diagnosis. In addition, the high rate of unidentified diagnoses suggests a need for further study into both non-infectious and infectious causes of equine abortion, including potential development of new diagnostic tests or markers., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Listeria monocytogenes ( Lm ) is a bacterial pathogen that causes listeriosis in immunocompromised individuals, particularly pregnant women. Several virulence factors support the intracellular lifecycle of Lm and facilitate cell-to-cell spread, allowing it to occupy multiple niches within the host and cross-protective barriers, including the placenta. One family of virulence factors, internalins, contributes to Lm pathogenicity by inducing specific uptake and conferring tissue tropism. Over 25 internalins have been identified thus far, but only a few have been extensively studied. Internalins contain leucine-rich repeat (LRR) domains that enable protein-protein interactions, allowing Lm to bind host proteins. Notably, other Listeria species express internalins but cannot colonize human hosts, prompting questions regarding the evolution of internalins within the genus Listeria . Internalin P (InlP) promotes placental colonization through interaction with the host protein afadin. Although prior studies of InlP have begun to elucidate its role in Lm pathogenesis, there remains a lack of information regarding homologs in other Listeria species. Here, we have used a computational evolutionary approach to identify InlP homologs in additional Listeria species. We found that Listeria ivanovii londoniensis ( Liv ) and Listeria seeligeri ( Ls ) encode InlP homologs. We also found InlP-like homologs in Listeria innocua and the recently identified species Listeria costaricensis . All newly identified homologs lack the full-length LRR6 and LRR7 domains found in Lm 's InlP. These findings are informative regarding the evolution of one key Lm virulence factor, InlP, and serve as a springboard for future evolutionary studies of Lm pathogenesis as well as mechanistic studies of Listeria internalins.

Coxiella burnetii is an intracellular bacterial pathogen that can be associated with significant reproductive disease or acute mortality in livestock and wildlife. A novel marine mammal-associated strain of C. burnetii has been identified in pinnipeds of the northwestern Pacific Ocean. Little is known about C. burnetii infection in regard to reproductive success or population status. Our objective was to characterize the severity and extent of histologic lesions in 117 opportunistically collected placentas from presumed-normal northern fur seals (Callorhinus ursinus) in July 2011 on St. Paul Island, Alaska, US, where a high placental prevalence of C. burnetii had been reported. Sections were examined by histology and immunohistochemistry and impression smears with modified acid-fast stain. The nature and frequency of histologic changes were compared with target COM1 PCR-confirmed C. burnetii positive and negative placentas. Overall, histologic changes were similar to placental lesions described in aborting ruminants; however, changes were variable within and between placentas. Vasculitis and occasional intracellular bacteria were seen only in C. burnetii PCR-positive placentas. Dystrophic mineralization, edema, and inflammation were seen in PCR-positive and negative placentas, although they were statistically more common in PCR-positive placentas. Results suggest that C. burnetti and associated pathologic changes are multifocal and variable in placentas from these presumably live-born pups. Therefore, multiple sections of tissue from different placental areas should be examined microscopically, and screened by PCR, to ensure accurate diagnosis as the genomes per gram of placenta may not necessarily represent the severity of placental disease. These limitations should inform field biologists, diagnosticians, and pathologists how best to screen and sample for pathogens and histopathology in marine mammal placental samples., (© Wildlife Disease Association 2022.)

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym 'TORCH' (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission., (© 2021. Springer Nature Limited.)

Objective: To assess the available scientific evidence regarding the placental microbial composition of a healthy pregnancy, the quality of this evidence, and the potential relation between placental and oral microbiome., Materials and Methods: Data sources: MEDLINE and EMBASE up to August 1, 2019., Study Eligibility Criteria: Human subjects; healthy women; term deliveries; healthy normal birth weight; assessment of microorganisms (bacteria) in placental tissue; full research papers in English. The quality of the included studies was assessed by a modified Joanna Briggs Institute checklist for analytical cross-sectional studies., Results: 57 studies passed the inclusion criteria. Of these, 33 had a high risk of quality bias (e.g., insufficient infection control, lack of negative controls, poor description of the healthy cases). The remaining 24 studies had a low (N = 12) to moderate (N = 12) risk of bias and were selected for in-depth analysis. Of these 24 studies, 22 reported microorganisms in placental tissues, where Lactobacillus (11 studies), Ureaplasma (7), Fusobacterium (7), Staphylococcus (7), Prevotella (6) and Streptococcus (6) were among the most frequently identified genera. Methylobacterium (4), Propionibacterium (3), Pseudomonas (3) and Escherichia (2), among others, although frequently reported in placental samples, were often reported as contaminants in studies that used negative controls., Conclusions: The results support the existence of a low biomass placental microbiota in healthy pregnancies. Some of the microbial taxa found in the placenta might have an oral origin. The high risk of quality bias for the majority of the included studies indicates that the results of individual papers should be interpreted with caution., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To study the inflammatory profile and genes involved in the response to bacterial infections in women who developed spontaneous abortion in the presence of Ureaplasma parvum., Design: Cross-sectional study., Setting: A maternal and child referral center., Patient(s): Eighty-nine women with spontaneous abortion and 20 women with normal vaginal delivery (control group) were studied., Intervention(s): Samples of biopsied placental tissue were collected for Mollicutes detection., Main Outcome Measure(s): The samples were subjected to histologic analysis, immunohistochemical evaluation for macrophages and lymphocytes, cytokine quantification, and quantitative polymerase chain reaction array to evaluate the expression of 84 genes related to the innate and adaptive immune responses., Result(s): The presence of U. parvum in the abortion group was positively associated with the influx of polymorphonuclear cells in the placental tissue and increased concentrations of interleukin-6 and interleukin-12p70. U. parvum caused downregulation of genes involved in the immune response, such as attraction of immune cells, activation of an inflammatory response, T-helper cell 17 response activation, and activation of the complement system at the beginning and end of pregnancy., Conclusion: The direct action of U. parvum on placental tissue altered the gestational tolerogenic state, reducing the immune response against pathogens and activating the extrinsic apoptotic pathway, causing spontaneous abortion., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We critically evaluated the fetal microbiome concept in 44 neonates with placenta, amniotic fluid, and first-pass meconium samples. Placental histology showed no signs of inflammation. Meconium samples were more often bacterial culture positive after vaginal delivery. In next-generation sequencing of the bacterial 16S gene, before and after removal of extracellular and PCR contaminant DNA, the median number of reads was low in placenta (48) and amniotic fluid (46) and high in meconium samples (14,556 C-section, 24,860 vaginal). In electron microscopy, meconium samples showed extracellular vesicles. Utilizing the analysis of composition of microbiomes (ANCOM) against water, meconium samples had a higher relative abundance of Firmicutes, Lactobacillus, Streptococcus, and Escherichia-Shigella. Our results did not support the existence of the placenta and amniotic fluid microbiota in healthy pregnancies. The first-pass meconium samples, formed in utero, appeared to harbor a microbiome that may be explained by perinatal colonization or intrauterine colonization via bacterial extracellular vesicles., (© 2021. The Author(s).)

Salmonella enterica subspecies diarizonae serovar 61:(k):1, 5, (7) (sheep associated S. diarizonae, SASd) is the most common Salmonella serotype identified in sheep flocks. Despite the involvement with animal and human infections, there is limited information regarding virulence profiles of SASds and their antibiotic resistance gene complement, particularly for those circulating in the U.S. In this study, we genetically characterized three SASds, 20-265, 20-269, and 20-312, isolated from sheep placental tissues during an abortion storm affecting a flock in Connecticut during 2020. SASds were the only bacteria isolated from analyzed sheep tissues. The isolates were sensitive to all the antibiotics tested, but all these SASd isolates carry the aminoglycoside resistance gene, aac(6')-Iaa, and a chromosomal substitution in the parC gene. The proportion of pseudogenes (5.3-5.5%) was similar among the isolates, and these SASds carry IncX1 type plasmids. Comparing with the SASds isolates from Enterobase, the three isolates showed an identical genomic virulence profile carrying virulence genes in the conserved set of other SASd isolates except for steC, iagB, iacP, sseI, and slrP genes. In the SNP-based phylogenetic analysis, SASd sequences were grouped into group A-C, and the group C was further subdivided into subgroup C1-C6. The three isolates clustered with other SASd isolates from the U.S. and Canada in subgroup C6. SASd isolates in the identical phylogenetic groups tended to have similar geographical origin. The results of our study did not provide conclusive evidence about which are the genetic traits that trigger SASds to become virulent in sheep, but our data will provide a point for comparative studies of this Salmonella serovar., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Investigators have long been interested in the natural phenomenon of fetal and placental cell trafficking into the maternal circulation. The scarcity of these circulating cells makes their detection and isolation technically challenging. However, as a DNA source of fetal origin not mixed with maternal DNA, they have the potential of considerable benefit over circulating cell-free DNA-based noninvasive prenatal genetic testing (NIPT). Endocervical trophoblasts, which are less rare but more challenging to recover are also being investigated as an approach for cell-based NIPT. We review published studies from around the world describing both forms of cell-based NIPT and highlight the different approaches' advantages and drawbacks. We also offer guidance for developing a sound cell-based NIPT protocol., (© 2021 John Wiley & Sons Ltd.)

The objective was to determine the relationship of histological chorioamnionitis (HCA) with genital tract cultures in preterm birth. Among two hundred women recruited for the study, 100 were taken as cases with gestational age between ≥28 and <37 weeks and 100 women with gestational age >37 weeks were taken as controls. Vaginal swabs were taken for culture sensitivity and vaginal smears were made for performing whiff test and heat dry gram stained smear was examined for growth of microorganisms. Histopathologic examination of the placenta was done after delivery. 49 cases and 26 controls had evidence of histological chorioamnionitis. A significant difference was observed in relation to the presence of E. coli , presence of clue cells, positive whiff test and occurrence of bacterial vaginosis in subjects with and without histological chorioamnionitis. Thus, we conclude that the presence of histological chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region.IMPACT STATEMENT What is already known on the subject? Histologic chorioamnionitis has been regarded to reflect amniotic fluid infection and there are studies showing an association between histologic chorioamnionitis, amniotic fluid, and subchorionic plate cultures. Nevertheless, studies of the correlation of the cervical swab cultures with intrauterine infection in preterm birth remain inconclusive. What do the results of this study add? Histologic chorioamnionitis is closely related to the presence of pathogenic microorganisms in the cervicovaginal region. What are the implications of these findings for clinical practice and/or further research? High vaginal swab cultures and gram staining of vaginal smear is useful in detecting antenatal patients who are at a higher risk for preterm labour. After detection, early intervention may be done to avoid preterm deliveries in these high-risk pregnancies.

Bacillus cereus is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal infections, including sepsis, meningitis, and pneumonia. Non-gastrointestinal B. cereus infections have been identified in children, especially in neonates; however, there are no previously described cases of fetal demise associated with B. cereus placental infection. We present a case of acute chorioamnionitis-related intrauterine fetal demise of twin A at 17 weeks gestation, noted two days after selective termination of twin B. Histological examination revealed numerous gram-positive bacilli in placental tissue, as well as fetal vasculature, in the setting of severe acute necrotizing chorioamnionitis and subchorionitis, intervillous abscesses, acute villitis, and peripheral acute funisitis. Cultures of maternal blood and placental tissue both yielded growth of B. cereus . This case underscores the importance of B. cereus as a human pathogen, and specifically demonstrates its potential as an agent of severe intraamniotic and placental infection with poor outcomes for the fetus.

Objectives: Preeclampsia is a dangerous pregnancy complication. The source of preeclampsia is unknown, though the placenta is believed to have a central role in its pathogenesis. An association between maternal infection and preeclampsia has been demonstrated, yet the involvement of the placental microbiome in the etiology of preeclampsia has not been determined. In this study, we examined whether preeclampsia is associated with an imbalanced microorganism composition in the placenta., Methods: To this end, we developed a novel method for the identification of bacteria/viruses based on sequencing of small non-coding RNA, which increases the microorganism-to-host ratio, this being a major challenge in microbiome methods. We validated the method on various infected tissues and demonstrated its efficiency in detecting microorganisms in samples with extremely low bacterial/viral biomass. We then applied the method to placenta specimens from preeclamptic and healthy pregnancies. Since the placenta is a remarkably large and heterogeneous organ, we explored the bacterial and viral RNA at each of 15 distinct locations., Results: Bacterial RNA was detected at all locations and was consistent with previous studies of the placental microbiome, though without significant differences between the preeclampsia and control groups. Nevertheless, the bacterial RNA composition differed significantly between various areas of the placenta. Viral RNA was detected in extremely low quantities, below the threshold of significance, thus viral abundance could not be determined., Conclusions: Our results suggest that the bacterial and viral abundance in the placenta may have only limited involvement in the pathogenesis of preeclampsia. The evidence of a heterogenic bacterial RNA composition in the various placental locations warrants further investigation to capture the true nature of the placental microbiome., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Salmonella foodborne disease during pregnancy causes a significant fetal loss in domestic livestock and preterm birth, chorioamnionitis and miscarriage in humans. These complications could be associated with alterations in placental structure. This study was aimed to determine how a low dose of Salmonella Enteritidis during late gestation affects placental histomorphometric in mice., Methods: We used a self-limiting enterocolitis murine model. BALB/c pregnant animals received a low dose of Salmonella Enteritidis (3-4 x 10 2  CFU/mouse) on gestational day (GD) 15. At day 3 post infection bacterial loads, serum cytokines expression and placental histomorphometrics parameters were analyzed., Results: We found that a sub-lethal infection with Salmonella induced a significant drop in fetal weight -to-placental weight-ratio and an increase in the placental coefficient. After bacterial inoculation maternal organs were colonized, inducing placental morphometric alterations, including increased placental thickness, reduced surface area, and diminished major and minor diameters. Also, foci of necrosis accompanied by acute leukocyte infiltration in decidual zone, reduction of vascular spaces and vascular congestion in labyrinth zone, were also evident in placentas from infected females on GD 18. Our data shows that placentas from infected mothers are phenotypically different from control ones. Furthermore, expression of IFN-gamma and IL-6 was up regulated in response to Salmonella in maternal serum., Discussion: Our findings demonstrate that a low dose of Salmonella during late gestation alters the placental morphometry leading to negative consequences on pregnancy outcome such as significant reduction in fetal body weight., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A novel Gram-stain-positive bacterium was isolated from a purulent bovine milk sample, the bovine placenta from an abortion, the udder secretion of a heifer and the lung of a pig that had succumbed from suppurative bronchopneumonia in Switzerland from 2015 to 2019. The strains grew best under aerobic conditions with 5 % CO 2 and colonies were non-haemolytic and greyish-white. They were non-motile and negative for catalase and oxidase. The genomes of the four strains 19M2397 T , 15A0121, 15IMD0307 and 19OD0592 were obtained by sequencing. The results of phylogenetic analyses based on the 16S rRNA gene grouped them within the genus Trueperella in the family Arcanobacteriaceae . The genomes had DNA G+C contents of 61.2-62.2 mol% and showed digital DNA-DNA hybridization (dDDH) values of 21.4-22.8 % and average nucleotide identity (ANI) values of approximately 77 % to their closest relatives Trueperella pyogenes and Trueperella bernardiae . With respect to the presence in different livestock species we propose the name Trueperella pecoris sp. nov. The type strain is 19M2397 T (=CCOS 1952 T =DSM 111392 T ), isolated from the udder secretion of a heifer diagnosed with summer mastitis in 2019.

This study aimed to investigate the association between microbiota found in the maternal gut and placenta, and whether ceftriaxone exposure during pregnancy could alter these microbiota, and consequently affect the immunity of the mothers and their offspring. The microbiota in the feces and placenta of the dams were comprehensively analyzed using16S rRNA sequencing. Furthermore, viable bacteria in the placentas and blood of pups were also isolated by plate cultivation then taxonomically identified in detail by clone sequencing. Serum cytokines collected from dams and pups were quantitatively profiled using Luminex. The spleen organ index of dams was significantly lower and the offspring serum interleukin-6 levels were significantly higher in ceftriaxone-treated mice compared with the control group. The maternal fecal microbiota community was drastically altered in ceftriaxone-treated mice with significantly decreased diversity, depletion of Bacteroidetes and the blooming of Tenericutes. However, the placenta microbiota was dominated by Proteobacteria especially characteristically by Ralstonia, which was distinct from the maternal gut microbiota, regardless of whether ceftriaxone treatment or not. Viable bacteria have been found in placenta and blood cultures. These results indicated that ceftriaxone exposure in pregnancy could dramatically alter maternal intestinal microbiota, which affected the immunity of the mothers and their offspring at least partly, characteristically by enhanced pro-inflammatory responses. This study also indicated that the placenta might harbor its own microbes and the microbes were distinct from maternal gut microbiota, which may not be affected by oral administration of ceftriaxone during pregnancy.

Background: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a "dysbiotic" polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse models of group B Streptococcus and Gardnerella vaginalis colonization have been reported but, to the best of our knowledge, the two have not been studied together. The overarching idea driving this study is that certain members of the dysbiotic vaginal microbiota, such as Gardnerella vaginalis, may directly contribute to the increased rate of group B Streptococcus vaginal colonization observed in women with vaginal dysbiosis., Objective: We used a mouse model to test the hypothesis that vaginal exposure to Gardnerella vaginalis may facilitate colonization and/or invasive infection of the upper reproductive tract by group B Streptococcus during pregnancy., Study Design: Timed-pregnant mice were generated using an allogeneic mating strategy with BALB/c males and C57Bl/6 females. Dams were vaginally inoculated at gestational day 14 with group B Streptococcus alone (using a 10-fold lower dose than previously reported models) or coinoculated with group B Streptococcus and Gardnerella vaginalis. Bacterial titers were enumerated in vaginal, uterine horn, and placental tissues at gestational day 17. The presence (Fisher exact tests) and levels (Mann-Whitney U tests) of bacterial titers were compared between mono- and coinoculated dams in each compartment. Relative risks were calculated for outcomes that occurred in both groups. Tissue samples were also examined for evidence of pathophysiology., Results: Inoculation of pregnant mice with 10 7 group B Streptococcus alone did not result in vaginal colonization or ascending infection. In contrast, coinoculation of group B Streptococcus with Gardnerella vaginalis in pregnant mice resulted in a 10-fold higher risk of group B Streptococcus vaginal colonization (relative risk, 10.31; 95% confidence interval, 2.710-59.04; P=.0006 [Fisher exact test]). Ascending group B Streptococcus infection of the uterus and placenta occurred in approximately 40% of coinoculated animals, whereas none of those receiving group B Streptococcus alone developed uterine or placental infections. Immunofluorescence microscopy revealed group B Streptococcus in both the maternal and fetal sides of the placenta. Histologic inflammation and increased proinflammatory cytokines were evident in the setting of group B Streptococcus placental infection. Interestingly, placentas from dams exposed to group B Streptococcus and Gardnerella vaginalis, but without recoverable vaginal or placental bacteria, displayed distinct histopathologic features and cytokine signatures., Conclusion: These data suggest that Gardnerella vaginalis vaginal exposure can promote group B Streptococcus vaginal colonization, resulting in a greater likelihood of invasive perinatal group B Streptococcus infections. These findings suggest that future clinical studies should examine whether the presence of Gardnerella vaginalis is a risk factor for group B Streptococcus vaginal colonization in women. Because Gardnerella vaginalis can also be present in women without bacterial vaginosis, these findings may be relevant both inside and outside of the context of vaginal dysbiosis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies., Objective: This study aimed to investigate the existence and origin of a placental microbiome., Study Design: A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments., Results: There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth., Conclusion: We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Intrauterine growth restriction (IUGR) is an obstetrical complication with an increased risk of perinatal mortality and morbidity. The uterus, once considered to be a sterile environment, has now been described in recent microbiome studies to harbor diverse commensal placenta microbiota, as well as potentially pathogenic flora known to cause infection. Therefore, in this pilot study, we tested whether IUGR was associated with changes to the reproductive microbiome. The reproductive microbiome was surveyed using 16S sequencing (20 IUGR, 20 controls). Alpha and beta diversity were compared, and differential taxa features associated with IUGR were identified. Microbial screening of the placenta demonstrated a diverse range of flora predominantly including Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes. Neither alpha- nor beta-diversity was significantly different by IUGR status. However, at the taxa level, IUGR patients had significantly higher prevalence of Neisseriaceae, mucosal β-hemolytic bacteria known to uptake iron-bound host proteins including hemoglobin. Moreover, the increase in anaerobic bacteria such as Desulfovibrio reflects the emergence of a hypoxic environment in the IUGR placenta. Further analysis of the reproductive microbiome of IUGR samples showed lower levels of H 2 0 2 -producing Bifidobacterium and Lactobacillus that switch from respiration to fermentation, a less energetic metabolic process, when oxygen levels decrease. Source tracking analysis showed that the placental microbial contents were predominantly contributed from an oral source, as compared to a gut or vaginal source. Our results suggest that the reproductive microbiome profiles may, in the future, constitute potential biomarkers for fetal health during pregnancy, while Neisseriaceae may constitute promising therapeutic targets for IUGR treatment.

Listeria monocytogenes (Lm) is a foodborne bacterial pathogen that causes listeriosis, a severe infection that manifests as bacteremia and meningo-encephalitis mostly in immunocompromised individuals, and maternal-fetal infection. A critical pathogenic determinant of Lm relies on its ability to actively cross the intestinal barrier, disseminate systemically and cross the blood-brain and placental barriers. Here we illustrate how Lm both evades innate immunity, favoring its dissemination in host tissues, and triggers innate immune defenses that participate to its control., (Copyright © 2020 Elsevier Ltd. All rights reserved.)