Placental Structure Research Articles

Comparison of pregnancy outcomes and placental characteristics for monochorionic diamniotic twins with and without proximate umbilical cord insertion

IntroductionThis study was developed to evaluate the relative placental characteristics and pregnancy outcomes associated with monochorionic diamniotic (MCDA) twins with and without proximate umbilical cord insertion (PCI). MethodsAll MCDA twins delivered with complete placentas for whom placental characteristics were assessed via dye injection between April 1, 2013 and April 1, 2021 were included in the present cohort study. Cases were separated into PCI and non-PCI groups, and pregnancy outcomes and placental characteristics were then compared between these groups. ResultsBirthweight discordance rates were significantly lower in the PCI group relative to the non-PCI group (7.3 ± 7.5% vs 29.9 ± 16.8%, P＜0.001), while relative to the non-PCI group, rates of artery-artery (AA), vein-vein (VV), thick AA, and thick VV anastomoses were significantly higher in the PCI group (95.5% vs 67.0%, P = 0.008, 59.1% vs 16.4, P＜0.001,90.5% vs 34.9%, P＜0.001, 54.5% vs 10.5%, P＜0.001). Significantly more anastomoses were observed in the PCI group (7 (3,11) vs 6 (3,15), P = 0.015), and they were significantly larger on average than those in the non-PCI group 12.8 (6.7,21.3) mm vs 11.9 (3.4, 24.6) mm, P = 0.009). Significantly lower placental territory discordance and UCI ratios were evident in the PCI group relative to the non-PCI group (23.5 (15.0,51.0) % vs 60.0 (2.0,80.0) %, P＜0.001, 13.3 ± 5.8% vs 56.1 ± 18.0%, P < 0.001). Marginal cord insertion rates were lower in the PCI group relative to the non-PCI group (13.6% vs 77.5%, P < 0.001). DiscussionThe placental structure of MCDA twins with PCI is distinct from that of twins without PCI, and these results suggest PCI may be indicative of the more even distribution of placental territory between MCDA fetuses.

Maternal PUFAs, Placental Epigenetics, and Their Relevance to Fetal Growth and Brain Development.

Dietary polyunsaturated fatty acids (PUFAs), especially omega-3 (n-3) and n-6 long-chain (LC) PUFAs, are indispensable for the fetus' brain supplied by the placenta. Despite being highly unsaturated, n-3 LCPUFA-docosahexaenoic acid (DHA) plays a protective role as an antioxidant in the brain. Deficiency of DHA during fetal development may cause irreversible damages in neurodevelopment programming. Dietary PUFAs can impact placental structure and functions by regulating early placentation processes, such as angiogenesis. They promote remodeling of uteroplacental architecture to facilitate increased blood flow and surface area for nutrient exchange. The placenta's fatty acid transfer depends on the uteroplacental vascular development, ensuring adequate maternal circulatory fatty acids transport to fulfill the fetus' rapid growth and development requirements. Maternal n-3 PUFA deficiency predominantly leads to placental epigenetic changes than other fetal developing organs. A global shift in DNA methylation possibly transmits epigenetic instability in developing fetuses due to n-3 PUFA deficiency. Thus, an optimal level of maternal omega-3 (n-3) PUFAs may protect the placenta's structural and functional integrity and allow fetal growth by controlling the aberrant placental epigenetic changes. This narrative review summarizes the recent advances and underpins the roles of maternal PUFAs on the structure and functions of the placenta and their relevance to fetal growth and brain development.

Large-scale placenta DNA methylation integrated analysis reveals fetal sex-specific differentially methylated CpG sites and regions

Although male–female differences in placental structure and function have been observed, little is understood about their molecular underpinnings. Here, we present a mega-analysis of 14 publicly available placenta DNA methylation (DNAm) microarray datasets to identify individual CpGs and regions associated with fetal sex. In the discovery dataset of placentas from full term pregnancies (N = 532 samples), 5212 CpGs met genome-wide significance (p < 1E−8) and were enriched in pathways such as keratinization (FDR p-value = 7.37E−14), chemokine activity (FDR p-value = 1.56E−2), and eosinophil migration (FDR p-value = 1.83E−2). Nine differentially methylated regions were identified (fwerArea < 0.1) including a region in the promoter of ZNF300 that showed consistent differential DNAm in samples from earlier timepoints in pregnancy and appeared to be driven predominately by effects in the trophoblast cell type. We describe the largest study of fetal sex differences in placenta DNAm performed to date, revealing genes and pathways characterizing sex-specific placenta function and health outcomes later in life.

Relationship of individual and mixed prenatal phthalate exposure with placental structure and efficiency in the prospective Ma'anshan Birth Cohort Study

BackgroundFew studies have investigated the associations between prenatal phthalate exposure and placental structure and function with inconsistent conclusions. MethodsNested on the Ma'anshan Birth Cohort study, 2723 women provided spot urine samples during the first, second and third trimesters of pregnancy to analyze six phthalate metabolites. The outcomes of interest were placental weight, efficiency (birth weight/placental weight), chorionic disc area and disc eccentricity. The relationships of prenatal exposure to a single phthalate with placental measures were analyzed. The associations between prenatal phthalate mixture exposure and placental measures were also evaluated. ResultsMost phthalate metabolites were significantly associated with placental weight, efficiency and chorionic disc area during the whole gestation and in each trimester of pregnancy, with different directions of relationships. Sensitivity analyses revealed similar findings, indicating the robustness of the statistical results. Furthermore, inverted U-shaped nonlinear relationships of prenatal exposure to some phthalate metabolites with placental weight, efficiency and chorionic plate area were observed. However, quantile g-computation mixture models did not reveal any association between maternal combined exposure to the total phthalate metabolites and placental measures. ConclusionsMaternal exposure to most phthalates and their metabolites was associated with placental weight, efficiency and chorionic plate area in both a linear manner and an inverted U-shaped nonlinear manner. However, the mixture of multiple phthalate metabolites was not observed to be associated with any placental measure.

Endocytosis-mediated vitellogenin absorption and lipid metabolism in the hindgut-derived placenta of the viviparous teleost Xenotoca eiseni

Certain viviparous animals possess mechanisms for mother-to-embryo nutrient transport during gestation. Xenotoca eiseni is one such viviparous teleost species in which the mother supplies proteins and other components to the offspring developing in the ovary. The embryo possesses trophotaenia, hindgut-derived placental structure, to receive the maternal supplement. However, research on the molecular mechanisms underlying viviparous species is scarce in non-mammalian vertebrates, including teleosts. Thus, we conducted this study to investigate the mechanism for nutrient absorption and degradation in trophotaeniae of X. eiseni. A tracer assay indicated that a lipid transfer protein, vitellogenin (Vtg), was absorbed into the epithelial layer cells of the trophotaeniae. Vtg uptake was significantly suppressed by Pitstop-2, an inhibitor of clathrin-mediated endocytosis. Gene expression analysis indicated that the genes involved in endocytosis-mediated lipolysis and lysosomal cholesterol transport were expressed in the trophotaeniae. In contrast, plasma membrane transporters expressed in the intestinal tract were not functional in the trophotaeniae. Our results suggested that endocytosis-mediated lysosomal lipolysis is one of the mechanisms underlying maternal component metabolism. Thus, our study demonstrated how viviparous teleost species have acquired a unique developmental system that is based on the hindgut-derived placenta.

Comparative Characteristics of Sialoglycans Expression Disorders in the Placental Barrier Structures in Preeclampsia and Fetal Growth Restriction.

We compared the expression profiles of α2,3- and α2,6-sialoglycans in the glycocalyx of the placental barrier structures in early and late forms of preeclampsia and fetal growth restriction using the method of lectin histochemistry. It was found that the expression of α2,3-sialoglycans in the syncytiotrophoblast and fetal endothelium of the terminal villi of the placenta was reduced in preeclampsia in comparison with normal placenta and, on the contrary, was increased in fetal growth restriction. Significant differences were found in both clinical phenotypes of preeclampsia and fetal growth restriction. Changes in the expression pattern of α2,6-sialoglycans in the endothelium of terminal villi were more pronounced than in syncytiotrophoblast. In early and late-onset preeclampsia, a significant increase in the expression of α2,6-sialoglycans was revealed only in the fetal endothelium; in early fetal growth restriction, the expression of α2,6-sialoglycans was reduced in the endothelium, but increased in syncytiotrophoblast in late fetal growth restriction. The features of the expression of sialoglycans in structures of the placental barrier in preeclampsia and fetal growth restriction were revealed, which may indicate the pathogenetic involvement of sialoglycans in the inflammatory activation cascade in fetal growth restriction, and in preeclampsia, apparently, they are associated with impaired fetal tolerance.

New insights on folliculogenesis and follicular placentation in marine viviparous fish black rockfish (Sebastes schlegelii).

In viviparous fish, a considerable degree of variation in placental structures have been described. However, no distinct structures are reported in Scorpaenidae. In this study, we demonstrate a new type of folliculogenesis and follicular placentation in Sebastes schlegelii. Before copulation, the germinal epithelium gradually surrounds the oocytes and develops into individually follicles with a stalk-like structure hanging on the ovigerous lamella, which ensures each follicle have access to spermatozoa after copulation. From V to early gestation stage, the cyp17-I highly expressesaccompanied by cyp19a1a signals disappearance, and 11-ketotestosterone level keeps rising and peaks at blastula stage, while 17β-estradiol declines to the bottom. Meanwhile, the theca cells rapidly proliferate and invade outwards forming a highly hypertrophied and folded microvillous placenta. This unbalance of hormone might be an important factor driving the theca cells proliferation and invasion. Additionally, some conserved genes related to mammalian placentation are significantly high expression in follicular placenta suggesting the high convergence in vertebrate placenta evolution.

Ex vivo dual perfusion of an isolated human placenta cotyledon: Towards protocol standardization and improved inter-centre comparability

Since the full development of the ex vivo dual perfusion model of the human placenta cotyledon, the technique has provided essential insight into how nutrients, lipids, gases, immunoglobulins, endocrine agents, pharmaceuticals, chemicals, nanoparticles, micro-organisms and parasites might traverse the maternofetal barrier. Additionally, the model has been instrumental in gaining a better understanding of the regulation of vascular tone, endocrinology and metabolism within this organ. The human placenta is unique amongst species in its anatomy and transfer modalities. This orthologous diversity therefore requires an appropriate consideration of placental transfer rates of compounds, particles and micro-organisms specific to humans.Different research centres have adapted this model with a wide variation in perfusion parameters, including in the establishment of perfusion, perfusate composition, gassing regime, cannulation method, flow rates, perfused tissue mass, and also in the application of quality control measures. The requirement to harmonise and standardise perfusion practice between centres is largely driven by the need to obtain consistency in our understanding of placental function, but also in the qualification of the model for acceptance by regulatory agencies in drug and toxicology testing.A pilot study is proposed, aiming to describe how existing inter-centre variation in perfusion methodology affects placental metabolism, protein synthesis, oxygen consumption, the materno-fetal transfer of key molecular markers, and placental structure.

Reduced O-linked n-acetyl-glucosamine (O-GLCNAC) in consequence of decreased placental nutritional apport affects the placental structure and fetal growth during pregnancy in hypertensive rats

Reduced O-linked n-acetyl-glucosamine (O-GLCNAC) in consequence of decreased placental nutritional apport affects the placental structure and fetal growth during pregnancy in hypertensive rats

Sexual dimorphism in placental development and function: Comparative physiology with an emphasis on the pig.

Across mammalian species, it has been demonstrated that sex influences birth weight, with males being heavier than females; a characteristic that can be observed from early gestation. Male piglets are more likely to be stillborn and have greater preweaning mortality than their female littermates, despite the additional maternal investment into male fetal growth. Given the conserved nature of the genome between the sexes, it is hypothesized that these developmental differences between males and females are most likely orchestrated by differential placental adaptation. This review summarizes the current understanding of fetal sex-specific differences in placental and endometrial structure and function, with an emphasis on pathways found to be differentially regulated in the pig including angiogenesis, apoptosis, and proliferation. Given the importance of piglet sex in agricultural enterprises, and the potential for skewed litter sex ratios, it is imperative to improve understanding of the relationship between fetal sex and molecular signaling in both the placenta and endometria across gestation.

Maternal exposure to ambient PM2.5 causes fetal growth restriction via the inhibition of spiral artery remodeling in mice

BackgroundMaternal exposure to ambient fine particulate matters (PM2.5) is associated with low birth weight (LBW) in offspring, but the underlying biological mechanisms are not yet fully understood. As the bridge that connects mother and fetus, the placenta plays a crucial role in fetal development by providing the fetus with nutrients and oxygen. However, whether PM2.5 exposure would impact the placental development and the related mechanisms are unclear. ResultsIn the present study, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and the fetal development and placental structure were investigated. Our results showed that maternal exposure to CAP induced fetal growth restriction (FGR) and LBW. The placenta from CAP-exposed mice exhibited abnormal development including significant decrease of surface area, smaller junctional zone and impaired spiral artery remodeling. Meanwhile, CAP exposure altered trophoblast lineage differentiation and disrupted the balance between angiogenic and angiostatic factors in placenta. In addition, the inflammatory cytokines levels in lung, placenta and serum were significantly increased after ambient PM2.5 exposure. ConclusionOur findings indicate that maternal exposure to PM2.5 disrupts normal structure and spiral artery remodeling of placenta and further induces FGR and LBW. This effect may be caused by the placental inflammation response subsequent to the pulmonary and systemic inflammation induced by ambient PM2.5 exposure.

Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism†.

Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8–10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ~60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver.

Preeclampsia associated changes in volume density of fetoplacental vessels in Chinese women and mouse model of preeclampsia

Preeclampsia (PE) is associated with abnormal placental vascular structure. However, the volume density of fetoplacental vessels in PE remains unclear. Additionally, manually annotated CT angiography, which is widely used to analyze placental vessels, has issues regarding inaccuracy. Thus, computer-aided CT angiography for analyzing the volume density of fetoplacental vessels would facilitate the understanding of PE pathogenesis. We performed computer-aided CT angiography to compare differences in placentas among 17 women with PE and 34 normotensive women. The contrast ratio in CT angiography was significantly enhanced using a three-dimensional (3-D) Hessian matrix algorithm. The PE-like mouse model was established by administration of 125mg/kg/day NG-nitro-l-arginine methyl ester (l-NAME) for 10 days. The presence of endothelial marker CD31 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The expression of angiogenic factors (PlGF, VEGFA, and sFlt1) in placentas was detected using qRT-PCR and western blotting. The volume density in fetoplacental vessels and CD31 expression were significantly reduced in women with PE and l-NAME-induced mice. Additionally, the downregulation of angiogenic factors (PlGF/VEGFA) and upregulation of an anti-angiogenic factor (sFlt1) were determined in a mouse model. Contrast-enhanced CT angiography with the aid of a 3-D Hessian matrix algorithm was performed. PE significantly affects the formation of vascular vessels, resulting in a lower volume density of fetoplacental vessels in humans and mice. This may be explained by the abnormal release of angiogenic factors during PE.

Spontaneous embryonic death in plains viscacha (Lagostomus maximus - Rodentia), a species with unique reproductive characteristics

Spontaneous embryonic death is a conserved reproductive event in Eutherians. The macro and microscopic characteristics of this type of death are similar between the different taxa. However, in the hystricomorphic rodent plains viscacha (Lagostomus maximus) is exceptional in terms of massiveness (80% embryonic resorption). In this species, of the 10–12 implantation sites (IS) (half in each uterine horn), only the caudal embryos will survive, resorbing the cranial and intermediate IS. We hypothesize that uterine structural variations in L. maximus restrict growth and promote embryo death, with the consequent loss of placental homeostasis in the cranial and middle IS. In this study, different studies (ultrasonography, macroscopy and microscopy) were carried out to analyze different aspects of the intermediate gestation of L. maximus (46 days postcoitus). Ultrasonographic studies revealed that the cranial and middle IS (IS-1, IS-2, and IS-3) had no recognizable embryonic and placental structures as compared to the caudal implantation sites (IS-4). Macroscopically, the areas corresponding to the embryos in the cranial and middle IS were occupied by a necrotic black semi-fluid mass. Moreover, the placenta in these IS was undifferentiated. However, in the caudal IS both the embryo and its placenta were distinguishable. Using histological and immunohistochemical techniques, it was observed that the placentas of IS-1, IS-2 and IS-3 were disorganized and showed hemorrhage, inflammatory infiltration containing neutrophils, macrophages, mast cells and foreign body giant cells, apoptotic trophoblast, and a layer of collagen fibers and fibroblasts that circumscribed each of these IS. In contrast, the placenta of the caudal IS showed an organized maternal-embryonic interface. The characteristics observed in IS in resorption of viscachas in intermediate gestation show that, regardless of gestation time, embryonic death has a similar macro and microscopic morphological pattern among eutherians with invasive placentation. However, the massiveness and sectorization of embryonic death in the plains viscacha make the species a unique model for the study of this reproductive event.

A New Approach in Detectability of Microcalcifications in the Placenta during Pregnancy Using Textural Features and K-Nearest Neighbors Algorithm.

(1) Background: Ultrasonography is the main method used during pregnancy to assess the fetal growth, amniotic fluid, umbilical cord and placenta. The placenta’s structure suffers dynamic modifications throughout the whole pregnancy and many of these changes, in which placental microcalcifications are by far the most prominent, are related to the process of aging and maturation and have no effect on fetal wellbeing. However, when placental microcalcifications are noticed earlier during pregnancy, they could suggest a major placental dysfunction with serious consequences for the fetus and mother. For better detectability of microcalcifications, we propose a new approach based on improving the clarity of details and the analysis of the placental structure using first and second order statistics, and fractal dimension. (2) Methods: The methodology is based on four stages: (i) cropping the region of interest and preprocessing steps; (ii) feature extraction, first order—standard deviation (SD), skewness (SK) and kurtosis (KR)—and second order—contrast (C), homogeneity (H), correlation (CR), energy (E) and entropy (EN)—are computed from a gray level co-occurrence matrix (GLCM) and fractal dimension (FD); (iii) statistical analysis (t-test); (iv) classification with the K-Nearest Neighbors algorithm (K-NN algorithm) and performance comparison with results from the support vector machine algorithm (SVM algorithm). (3) Results: Experimental results obtained from real clinical data show an improvement in the detectability and visibility of placental microcalcifications.

Placental structure, function, and mitochondrial phenotype relate to fetal size in each fetal sex in mice†.

Fetal growth depends on placental function, which requires energy from mitochondria. Here we investigated whether mitochondrial function in the placenta relates to the growth of the lightest and heaviest fetuses of each sex within the litter of mice. Placentas from the lightest and heaviest fetuses were taken to evaluate placenta morphology (stereology), mitochondrial energetics (high-resolution respirometry), mitochondrial regulators, nutrient transporters, hormone handling, and signaling pathways (qPCR and Western blotting). We found that mitochondrial complex I and II oxygen consumption rate was greater for placentas supporting the lightest female fetuses, although placental complex I abundance of the lightest females and complexes III and V of the lightest males were decreased compared to their heaviest counterparts. Expression of mitochondrial biogenesis (Nrf1) and fission (Drp1 and Fis1) genes was lower in the placenta from the lightest females, whilst biogenesis-related gene Tfam was greater in the placenta of the lightest male fetuses. In addition, placental morphology and steroidogenic gene (Cyp17a1 and Cyp11a1) expression were aberrant for the lightest females, but glucose transporter (Slc2a1) expression was lower in only the lightest males versus their heaviest counterparts. Differences in intra-litter placental phenotype were related to changes in the expression of hormone-responsive (androgen receptor) and metabolic signaling (AMPK, AKT, and PPARγ) pathways. Thus, in normal mouse pregnancy, placental structure, function, and mitochondrial phenotype are differentially responsive to the growth of the female and male fetus. This study may inform the design of sex-specific therapies for placental insufficiency and fetal growth abnormalities with life-long benefits for the offspring.

Lipidomic Analysis of TRPC1 Ca2+-Permeable Channel-Knock Out Mouse Demonstrates a Vital Role in Placental Tissue Sphingolipid and Triacylglycerol Homeostasis Under Maternal High-Fat Diet.

The transient receptor potential canonical channel 1 (TRPC1) is a ubiquitous Ca2+-permeable integral membrane protein present in most tissues, including adipose and placenta, and functionally regulates energetic homeostasis. We demonstrated that elimination of TRPC1 in a mouse model increased body adiposity and limited adipose accumulation under a high fat diet (HFD) even under conditions of exercise. Additionally, intracellular Ca2+ regulates membrane lipid content via the activation of the protein kinase C pathway, which may impact placental membrane lipid content and structure. Based upon this we investigated the effect of HFD and TRPC1 elimination on neutral lipids (triacylglycerol and cholesteryl ester), membrane lipids (phosphatidylcholine and phosphatidylethanolamine), and other multifunctional lipid species (unesterified cholesterol, sphingomyelins, ceramides). The concentration of unesterified cholesterol and sphingomyelin increased with gestational age (E12.5 to E 18.5.) indicating possible increases in plasma membrane fluidity. Diet-dependent increases ceramide concentration at E12.5 suggest a pro-inflammatory role for HFD in early gestation. TRPC1-dependent decreases in cholesterol ester concentration with concomitant increases in long-chain polyunsaturated fatty acid -containing triacylglycerols indicate a disruption of neutral lipid homeostasis that may be tied to Ca2+ regulation. These results align with changes in lipid content observed in studies of preeclamptic human placenta.

Differential expression of placental 11β-HSD2 induced by high maternal glucocorticoid exposure mediates sex differences in placental and fetal development

A variety of adverse environmental factors during pregnancy cause maternal chronic stress. Caffeine is a common stressor, and its consumption during pregnancy is widespread. Our previous study showed that prenatal caffeine exposure (PCE) increased maternal blood glucocorticoid levels and caused abnormal development of offspring. However, the placental mechanism for fetal development inhibition caused by PCE-induced high maternal glucocorticoid has not been reported. This study investigated the effects of PCE-induced high maternal glucocorticoid level on placental and fetal development by regulating placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) expression and its underlying mechanism. First, human placenta and umbilical cord blood samples were collected from women without prenatal use of synthetic glucocorticoids. We found that placental 11β-HSD2 expression was significantly correlated with umbilical cord blood cortisol level and birth weight in male newborns but not in females. Furthermore, we established a rat model of high maternal glucocorticoids induced by PCE (caffeine, 60 mg/kg·d, ig), and found that the expression of 11β-HSD2 in male PCE placenta was decreased and negatively correlated with the maternal/fetal/placental corticosterone levels. Meanwhile, we found abnormal placental structure and nutrient transporter expression. In vitro, BeWo cells were used and confirm that 11β-HSD2 mediated inhibition of placental nutrient transporter expression induced by high levels of glucocorticoid. Finally, combined with the animal and cell experiments, we further confirmed that high maternal glucocorticoid could activate the GR-C/EBPα-Egr1 signaling pathway, leading to decreased expression of 11β-HSD2 in males. However, there was no significant inhibition of placental 11β-HSD2 expression, placental and fetal development in females. In summary, we confirmed that high maternal glucocorticoids could regulate placental 11β-HSD2 expression in a sex-specific manner, leading to differences in placental and fetal development. This study provides the theoretical and experimental basis for analyzing the inhibition of fetoplacental development and its sex difference caused by maternal stress.

Environmental constraints and pathologies that modulate equine placental genes and development.

Equine placental development is a long process with unique features. Implantation occurs around 40 days of gestation (dpo) with the presence of a transient invasive placenta from 25-35 to 100-120 dpo. The definitive, non-invasive placenta remains until term (330 days). This definitive placenta is diffuse and epitheliochorial, exchanging nutrients, gas and waste with the endometrium through microvilli, called microcotyledons. These are lined by an external layer of haemotrophic trophoblast. Moreover, histotrophic exchange remains active through the histotrophic trophoblast located along the areolae. Placental development is dependent on the maternal environment that can be affected by several factors (e.g. nutrition, metabolism, age, embryo technologies, pathologies) that may affect fetal development as well as long-term offspring health. The first section of the review focuses on normal placental development as well as definitive placental structure. Differences between the various regions of the placenta are also highlighted. The latter sections provide an overview of the effects of the maternal environment and reproductive pathologies, respectively, on trophoblast/placental gene expression and structure. So far, only pre-implantation and late gestation/term data are available, which demonstrate important placental plasticity in response to environmental variation, with genes involved in oxidative stress and tissue differentiation mostly involved in the pre-implantation period, whereas genes involved in feto-placental growth and nutrient transfers are mostly perturbed at term.

Vaginal Exposure to Candida albicans During Early Gestation Results in Adverse Pregnancy Outcomes via Inhibiting Placental Development.

Vulvovaginal candidiasis (VVC) is considered the second most common cause of vaginitis after bacterial vaginosis and the most common lower genital tract infection during pregnancy. Candida albicans (C. albicans), an opportunistic pathogen, is the major species causing VVC. Recently, increasing researches have shown that lower reproductive tract infection during pregnancy can lead to various adverse pregnancy outcomes. However, the underlying mechanisms are not fully understood. Hence, we successfully established a mouse model of vaginal C. albicans infection and characterized the adverse pregnancy outcomes. C. albicans infection strikingly increased abortion rate and decreased litter size. Further analysis of placental development demonstrated that placental structure was abnormal, including that the area of spongiotrophoblast (Spo) and labyrinth (Lab) was reduced, and the formation of placental vessel was decreased in Lab zone. Accordingly, the expression of marker genes during placental development was downregulated. Collectively, the above findings revealed that vaginal C. albicans infection during pregnancy can inhibit placental development and ultimately lead to adverse pregnancy outcomes. This study enhances our comprehension of the effect of VVC on pregnancy, and placental dysplasia as a feasible orientation to explore VVC during pregnancy.