Role Of Placenta Research Articles

Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming.

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.

With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types. We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases. We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal-fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types. Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreover, most of the newly defined markers in one study were not observed in other studies. These discrepancies were confirmed by our analysis on trophoblast cell types, where hundreds of potential marker genes were identified in each study but with little overlap across studies. From 35461 and 23378 cells of high quality in the first trimester and term placentas, respectively, we obtained major placental cell types, including perivascular cells that previously had not been identified in the first trimester. Importantly, our meta-analysis provides marker genes for major placental cell types based on our extensive curation. This review and meta-analysis emphasizes the need for establishing a consensus for annotating placental cell types from scRNAseq data. The marker genes identified here can be deployed for defining human placental cell types, thereby facilitating and improving the reproducibility of trophoblast cell annotation.

Maternal Vitamin B12 in Pregnancy and Placental Development.

Vitamin B12, or cobalamin, is an essential nutrient required for diverse physiological functions secondary to its role as a critical cofactor for two mammalian enzymes, methionine synthase and methylmalonyl-CoA mutase. While essential throughout all life stages, several pathways that require vitamin B12, including hematopoiesis, myelination, and DNA/histone methylation, are particularly critical during pregnancy and fetal development. This narrative review aims to describe vitamin B12 in pregnancy, with emphasis on the placenta's role in ensuring adequate nutrition of the fetus and impacts of vitamin B12 deficiency on placental development and function. Our literature search included preclinical model systems and human cohorts and interventions. Our review identified evidence of B12 deficiency resulting in impaired placental development, greater placental inflammation, and modulation of placental docosahexaenoic acid concentration, collectively suggestive of vitamin B12 deficiency as a determinant of both maternal and fetal health outcomes. Heterogeneity in study design complicated generalization of findings. Future studies should consider selecting a B12 marker that is relatively stable across pregnancy, such as holotranscobalamin, while accounting for important confounders such as maternal folate.

Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders.

Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety of neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence to support these mechanistic links, with placental inflammatory responses and dysregulation of placental function implicated. This leads to changes in fetal brain cytokine balance and altered epigenetic regulation of key neurodevelopmental pathways. The prenatal timing of such mIA-evoked changes, and the accompanying fetal developmental responses to an altered in utero environment, will determine the scope of the impacts on neurodevelopmental processes. Such dysregulation can impart enduring neuropathological changes, which manifest subsequently in the postnatal period as altered neurodevelopmental behaviours in the offspring. Hence, elucidation of the functional changes that occur at the molecular level in the placenta is vital in improving our understanding of the mechanisms that underlie the pathogenesis of NDDs. This has notable relevance to the recent COVID-19 pandemic, where inflammatory responses in the placenta to SARS-CoV-2 infection during pregnancy and NDDs in early childhood have been reported. This review presents an integrated overview of these collective topics and describes the possible contribution of prenatal programming through placental effects as an underlying mechanism that links to NDD risk, underpinned by altered epigenetic regulation of neurodevelopmental pathways.

Association of polycystic ovary syndrome with multiple health factors and adverse pregnancy outcomes

Polycystic ovary syndrome (PCOS), an endocrine and metabolic disorder in women of reproductive age, is characterized by high androgen levels, irregular periods, and small cysts in the ovaries. PCOS affects approximately 10% of reproductive age women of all races and ethnicities. PCOS has been recognized to affect women of reproductive age since antiquity and in the 21st century, it emerges as the most widespread and serious reproductive metabolic disorder in the world. PCOS is a multifactorial disorder that affects both the reproductive and metabolic health of women. In addition, PCOS is a leading symptom of infertility in women. Nevertheless, women with PCOS who become pregnant unfortunately have an increased risk of complications, such as gestational diabetes mellitus (GDM), preterm birth. Many people believe GDM disappears after childbirth, despite the fact that GDM is a warning symptom of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. According to growing evidence, GDM complicates 40% of PCOS pregnancies, suggesting that PCOS is a risk factor for GDM. Hence, PCOS is a lifelong disorder that can eventually lead to various long-term health complications, including chronic menstrual irregularity, infertility, endometrial hyperplasia, and endometrial cancer. Thus, it’s a scientific fact that both PCOS and GDM are significantly associated with each other. However, most studies on the risk of GDM in PCOS patients are retrospective. Therefore, there is no strong evidence whether PCOS is a risk factor for GDM or any other related factor. PCOS, a polygenic endocrinopathy, is in a true sense a set of diseases that worsen the state of the body. Reproductive and metabolic disorders associated with PCOS cause several clinical symptoms, such as irregular and painful periods, hirsutism, acanthosis nigricans, acne, psoriasis, anxiety, mood swings, patterned baldness, cardiovascular problems, type 2 diabetes, infertility, pelvic pain, low libido, low self-esteem, etc. Further studies are needed to understand the genetic and epigenetic contributions of PCOS, PCOS-related comorbidities, the role of placenta in nutrient availability, and influence of medications that may affect the long-term offspring health.

Phylogenomic analysis of cytochrome P450 multigene family and its differential expression analysis in pepper (Capsicum annuum L.).

Plant cytochrome P450 is a multifamily enzyme widely involved in biochemical reactions for the synthesis of antioxidants, pigments, structural polymers, and defense-related compounds. Pepper (Capsicum annuum L.) is an economically important plant. A comprehensive identification and characterization of P450 genes would provide valuable information on the evolutionary relationships of genes and their functional characteristics. In this study, we identified P450 genes in pepper with the aid of bioinformatics methods to investigate the phylogenetic relation, gene structure, chromosomal localization, duplicated events, and collinearity among Solanaceae species. We identified and classified 478 genes of P450 from the pepper genome into two major clades and nine subfamilies through phylogenetic analysis. Massive duplication events were found in the P450 gene family, which may explain the expansion of the P450 gene family. In addition, we also found that these duplication genes may have undergone strict purification selection during evolution. Gene expression analysis showed that some P450 genes that belong to clan 71 in pepper may play an important role in placenta and pericarp development. Through quantitative real-time polymerase chain reaction and transcriptome analysis, we also found that many P450 genes were related to defensive and phytohormone response in pepper. These findings provide insight for further studies to identify the biological functions of the P450 genes in pepper.

Histopathological and immunological characteristics of placentas infected with chikungunya virus.

Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1-4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-β and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.

ANNEXIN A1: Roles in Placenta, Cell Survival, and Nucleus.

The unbiased approaches of the last decade have enabled the collection of new data on the biology of annexin A1 (ANXA1) in a variety of scientific aspects, creating opportunities for new biomarkers and/or therapeutic purposes. ANXA1 is found in the plasma membrane, cytoplasm, and nucleus, being described at low levels in the nuclear and cytoplasmic compartments of placental cells related to gestational diabetic diseases, and its translocation from the cytoplasm to the nucleus has been associated with a response to DNA damage. The approaches presented here open pathways for reflection upon, and intrinsic clarification of, the modulating action of this protein in the response to genetic material damage, as well as its level of expression and cellular localization. The objective of this study is to arouse interest, with an emphasis on the mechanisms of nuclear translocation of ANXA1, which remain underexplored and may be beneficial in new inflammatory therapies.

Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia.

Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7–14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8–20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.

Maternal 3,3’-Diiodothyronine Sulfate Formation from Guinea Pig Placenta Perfused with 3,3’,5-Triodothyronine

Objective:Serum 3, 3’,5-triiodothyronine (T3) remains low in near-term fetus to prevent the growing fetus from undue exposure to its active catabolic effect in mammals. The present study was undertaken to gain insight in the role of placenta in T3 metabolism, fetal to maternal transfer of T3, and its metabolites by in situ placenta perfusion with outer-ring labeled [125I]-T3 in pregnant guinea pig, a species showing increased sulfated 3, 3’-diiodothyronine (T2S) levels in maternal serum in late pregnancy (term = 65 days), similarly to humans in pregnancy.Materials and Methods:One-pass placenta perfusions performed on pregnant guinea pigs were studied between 58 – 65 days of gestation. In two separate experiments, the umbilical artery of the guinea pig placenta was perfused in situ at 37°C with outer-ring labeled [125I]-T3. Maternal sera and umbilical effluents were obtained for analysis at the end of a 60-minute perfusion, when the steady-state levels of radioactivity were reached in the placenta effluent after 30-minute.Results:Sulfated [125I]-T2S was readily detected in the maternal serum as the major metabolite of T3 following the perfusion of placenta with [125I]-T3, suggesting that placental inner-ring deiodinase and sulfotransferase may play an important role in fetal T3 homeostasis and in the fetal to maternal transfer of sulfated iodothyronine metabolites.Conclusions:The expression of type 3 deiodinase (D3) and thyroid hormone sulfotransferase activity in placenta may play an important role to protect developing organs against undue exposure to active thyroid hormone in late gestation in the fetus. The combined activities of D3 and sulfotransferase promoted a placental transfer of T2S into maternal circulation. The maternal circulation of T2S is fetal T3 in origin and its role as a fetal thyroid function biomarker deserves further evaluations and studies.

Does exercise during pregnancy impact organs or structures of the maternal-fetal interface?

Exercise during pregnancy has been shown to be associated with improved health outcomes both during and after pregnancy for mother and fetus across the lifespan. Increasing physical activity and reducing sedentary behaviour during pregnancy have been recommended by many researchers and clinicians-alike. It is thought that the placenta plays a central role in mediating any positive or negative pregnancy outcomes. The positive outcomes obtained through prenatal exercise are postulated to result from exercise-induced regulation of maternal physiology and placental development. Considerable research has been performed to understand the placenta's role in pregnancy-related diseases, such as preeclampsia, fetal growth restriction, and gestational diabetes mellitus. However, little research has examined the potential for healthy lifestyle and behavioural changes to improve placental growth, development, and function. While the placenta represents the critical maternal-fetal interface responsible for all gas, nutrient, and waste exchange between the mother and fetus, the impact of exercise during pregnancy on placental biology and function is not well known. This review will focus on prenatal exercise and its promising influence on the structures of the maternal-fetal interface, with particular emphasis on the placenta. Potential molecular mechanistic hypotheses are presented to aid future investigations of prenatal exercise and placental health.

Role of placenta in development of pre-eclampsia: revisited.

Role of placenta in development of pre-eclampsia: revisited.

Buprenorphine Metabolism in Human Liver, Human Placenta, and Recombinant Cyp19 Microsomes

Background and Hypothesis: Buprenorphine (BUP), a partial opioid agonist, is commonly used to treat opioid use disorder in pregnant women. BUP is metabolized in the liver by cytochrome P450s (CYP) and UDPGlucuronosyltransferases (UGT). Compared to non-pregnant women, higher doses of BUP are needed during pregnancy to maintain therapeutic concentrations. We hypothesize that the placenta has a role in the metabolism of BUP, thus contributing to the need for higher doses during pregnancy.
 Experimental Design or Project Methods: : BUP was incubated with human liver microsome (HLM), human placenta microsome (HPM) or recombinant CYP19 microsome (rCYP19). Norbuprenorphine (Nor-BUP) formation was measured by HPLC/MS/MS (Thermo TSQ Quantum Ultra). Positive controls included midazolam for HLMs and testosterone for HPMs and rCYP19, and negative controls were without NADPH. Initial experiments assessed linearity with time and protein concentration. Subsequently, BUP concentrations were varied and Nor-BUP formation vs. BUP concentration was fitted to the Michaelis–Menten equation (GraphPad Prism) to calculate Km and Vmax.
 Results: The Km was 11.89 μM and Vmax was 0.4627 μmol/min/mg for Nor-BUP formation following incubation of BUP (0-20 µM) with HLM. Higher concentrations of BUP indicated non-typical Michaelis–Menten kinetics. Results from the HPM show metabolism of BUP to Nor-BUP is present in the placenta. Incubation of BUP in rCYP19, an enzyme known to be in human placenta, resulted in Nor-BUP formation, indicating its role in BUP metabolism.
 Conclusions and Potential Impact: : The Km and Vmax values generated from concentrations of 5-20 μM in HLM is comparable with existing data. Because multiple enzymes breakdown BUP with different Km and Vmax values, a curve not adhering to the normal Michaelis–Menten shape over 20 μM BUP is reasonable in HLMs. Formation of Nor-BUP following incubation of BUP in rCYP19 and HPMs suggest their role in the metabolism of BUP in pregnant women. Understanding the role of placenta in metabolizing BUP will provide insight to fetal drug exposure. Placental metabolism of BUP would possibly indicate lower exposure to BUP but higher exposure to nor-BUP to the fetus. Future directions of this study will quantify placental metabolism of BUP, investigate other pathways of BUP metabolism in the placenta, and determine drug interactions that may exacerbate Neonatal Abstinence Syndrome when coadministered with BUP.

Placental Studies for Child Development.

Research on children's psychological and behavioral development readily incorporates changing biological models and techniques. In this article, we suggest that, in response to increasing evidence of robust influences of prenatal exposures on children's neurodevelopment and mental and physical health, developmental science also needs to consider the placenta's role in development. We argue why placental mechanisms are plausible targets in developmental science, and suggest initial and practical steps toward integrating placenta markers and mechanisms into research on child development.

Cornelia de Lange syndrome, related disorders, and the Cohesin complex: Abstracts from the 8th biennial scientific and educational symposium 2018.

Cornelia de Lange Syndrome (CdLS), due to mutations in genes of the cohesin protein complex, is described as a disorder of transcriptional regulation. Phenotypes in this expanding field include short stature, microcephaly, intellectual disability, variable facial features and organ involvement, resulting in overlapping presentations, including established syndromes and newly described conditions. Individuals with all forms of CdLS have multifaceted complications, including neurodevelopmental, feeding, craniofacial, and communication. Coping mechanisms and management of challenging behaviors in CdLS, disruption of normal behaviors, and how behavior molds the life of the individual within the family is now better understood. Some psychotropic medications are known to be effective for behavior. Other medications, for example, Indomethacin, are being investigated for effects on gene expression, fetal brain tissue, brain morphology and function in Drosophila, mice, and human fibroblasts containing CdLS-related mutations. Developmental studies have clarified the origin of cardiac defects and role of placenta in CdLS. Chromosome architecture and cohesin complex structure are elucidated, leading to a better understanding of regulatory aspects and controls. As examples, when mutations are present, the formation of loop domains by cohesin, facilitating enhancer-promotor interactions, can be eliminated, and embryologically, the nuclear structure of zygotes is disrupted. Several important genes are now known to interact with cohesin, including Brca2. The following abstracts are from the 8th Cornelia de Lange Syndrome Scientific and Educational Symposium, held in June 2018, Minneapolis, MN, before the CdLS Foundation National Meeting, AMA CME credits provided by GBMC, Baltimore, MD. All studies have been approved by an ethics committee.

HERV-W group evolutionary history in non-human primates: characterization of ERV-W orthologs in Catarrhini and related ERV groups in Platyrrhini

BackgroundThe genomes of all vertebrates harbor remnants of ancient retroviral infections, having affected the germ line cells during the last 100 million years. These sequences, named Endogenous Retroviruses (ERVs), have been transmitted to the offspring in a Mendelian way, being relatively stable components of the host genome even long after their exogenous counterparts went extinct. Among human ERVs (HERVs), the HERV-W group is of particular interest for our physiology and pathology. A HERV-W provirus in locus 7q21.2 has been coopted during evolution to exert an essential role in placenta, and the group expression has been tentatively linked to Multiple Sclerosis and other diseases. Following up on a detailed analysis of 213 HERV-W insertions in the human genome, we now investigated the ERV-W group genomic spread within primate lineages.ResultsWe analyzed HERV-W orthologous loci in the genome sequences of 12 non-human primate species belonging to Simiiformes (parvorders Catarrhini and Platyrrhini), Tarsiiformes and to the most primitive Prosimians. Analysis of HERV-W orthologous loci in non-human Catarrhini primates revealed species-specific insertions in the genomes of Chimpanzee (3), Gorilla (4), Orangutan (6), Gibbon (2) and especially Rhesus Macaque (66). Such sequences were acquired in a retroviral fashion and, in the majority of cases, by L1-mediated formation of processed pseudogenes. There were also a number of LTR-LTR homologous recombination events that occurred subsequent to separation of Catarrhini sub-lineages. Moreover, we retrieved 130 sequences in Marmoset and Squirrel Monkeys (family Cebidae, Platyrrhini parvorder), identified as ERV1–1_CJa based on RepBase annotations, which appear closely related to the ERV-W group. Such sequences were also identified in Atelidae and Pitheciidae, representative of the other Platyrrhini families. In contrast, no ERV-W-related sequences were found in genome sequence assemblies of Tarsiiformes and Prosimians.ConclusionsOverall, our analysis now provides a detailed picture of the ERV-W sequences colonization of the primate lineages genomes, revealing the exact dynamics of ERV-W locus formations as well as novel insights into the evolution and origin of the group.

Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology

In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication.

Maternal exercise during pregnancy reduces the risk of preterm birth through the mediating role of placenta

Objective: The extent of research on maternal exercise during pregnancy and the risk of preterm birth (PTB) have grown substantially, but conclusions still remained controversial. Thus, this study aims to examine the relationship of maternal exercise during pregnancy and PTB and explore whether placenta mediates their relationship. Study design: We investigated 849 pregnant women delivering PTB newborns (cases) and 1306 delivering full-term appropriate for gestational age newborns (controls) in this case–control study. Information concerning maternal exercise during pregnancy, sociodemographics and obstetric characteristics were collected at Women and Children’s Hospitals of Shenzhen and Foshan in Guangdong, China. A series of logistic and linear regressions were used to examine the relationships of maternal exercise during pregnancy, placenta, and PTB. Results: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were negatively associated with PTB. Moreover, compared with mother taking no exercise during pregnancy, those taking exercise lowered the risk of PTB except those taking low/medium frequency and short duration exercise, and their adjusted ORs ranged from 0.43 to 0.65. Furthermore, mediation analysis illustrated that placental weight partially mediated 65.20% of the effects of maternal exercise frequency on PTB, as well as 41.98% of the association between maternal exercise duration and PTB. Conclusions: Maternal exercise during pregnancy is beneficial for lowering the risk of PTB, especially when taking appropriate and enough exercise. Placenta weight may partially mediate the association between maternal exercise during pregnancy and PTB.

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development.

ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13-von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.

Expression analysis of IL-15 as a candidate gene for placental efficiency in goats

In present study, functional relevance of IL-15 with goat placenta was determined by quantitative real-time PCR (SYBR Green chemistry) and western blot. The 486 bp full-length coding sequence of the gene, encoding 162 amino acids, was cloned. Expression of IL-15 was significantly higher in placenta, especially in cotyledon, than that in other neonatal tissues (P less than 0.05). In both Dazu Black and Inner Mongolia Cashmere breeds, IL-15 mRNA in cotyledon was up-regulated at term compare to that at day 30 of gestation (P less than 0.05), and was significantly different between both breeds (P less than 0.05). Additionally, IL-15 transcripts had a close relationship with that of vascular endothelial growth factor and a positive correlation with placental efficiency (R2=0.922, P=0.04), but it was negatively correlated with cotyledon density (R2=0.952, P=0.024). The results indicate that IL-15 is conserved in goats, and has important role in placenta, thereby can be a candidate gene for placental efficiency in goats.