Embryonic-placental relationship in Lagostomus maximus as compared to other hystricognath rodents and eutherian mammals.

Reproductive specializations in caviomorphs (infraorder Hystricognathi), are very peculiar within the Order Rodentia. These include long gestations, the birth of offspring with an extreme degree of precociality, and short lactation periods. This study describes the embryo-placental relationship of viable implantation sites (IS) of the plains viscacha, Lagostomus maximus, after 46 post-coital days. The observations recorded in this study are comparatively discussed with those of other hystricognaths and eutherians. At this stage, the embryo resembles that of other eutherians. At this time of embryo development, the placenta exhibits a size, shape, and organization similar to that it will have in its mature state. Besides, the subplacenta is already highly folded. These characteristics are adequate to sustain the development of future precocial offspring. The mesoplacenta, a structure present in other hystricognaths and related to uterine regeneration is described for the first time in this species. This detailed description of the placental and embryonic structure contributes to the knowledge of the reproductive and developmental biology of the viscacha, as well as that of hystricognaths. These characteristics will allow testing other hypotheses related to the morphology and physiology of the placenta and subplacenta, and their relationship with the growth and development of precocial offspring in Hystricognathi.

Automated segmentation and morphological characterization of placental intervillous space based on a single labeled image.

In this study, a novel method of data augmentation has been presented for the segmentation of placental histological images when the labeled data are scarce. This method generates new realizations of the placenta intervillous morphology while maintaining the general textures and orientations. As a result, a diversified artificial dataset of images is generated that can be used for training deep learning segmentation models. We have observed that on average the presented method of data augmentation led to a 42% decrease in the binary cross-entropy loss of the validation dataset compared to the common approach in the literature. Additionally, the morphology of the intervillous space is studied under the effect of the proposed image reconstruction technique, and the diversity of the artificially generated population is quantified. We have demonstrated that the proposed method results in a more accurate morphological characterization of the placental intervillous space with an average feature relative error of 6.5%, which is significantly lower than the 11.5% error observed with conventional augmentation techniques. Due to the high resemblance of the generated images to the real ones, applications of the proposed method may not be limited to placental histological images, and it is recommended that other types of tissue be investigated in future studies.

Placental glycotype of the caviomorph rodent Lagostomus maximus and its evolution within Eutheria.

The main evolutionary milestone in the oviparity-viviparity transition is placentation. The placenta is an organ with great morphological diversity among eutherians. The expression of different glycosidic residues (Gr) in the near-term placenta constitutes its glycotype. In this study, the expression of different Gr was determined by lectin histochemistry in early, midterm, and near-term placentas of the plains viscacha (Lagostomus maximus), a caviomorph rodent with the highest poliovulatory rate and embryonic resorption rate among eutherians. Besides, a matrix with the expression of each Gr in the exchange trophoblast of viscacha and other eutherians was constructed to map and infer phylogenetic and evolutionary relationships. Between early, midterm, and near-term placentas, variations in the pattern expression of Gr were observed. The glycotype of the near-term placenta is composed of a high diversity of Gr. Reconstruction of the ancestral state for each Gr present in the near-term placenta showed a diverse scenario: some sugars were common to the species of Placentalia included in this study. In the analyzed species with synepitheliochorial and epitheliochorial placentas, no differential glycosylation patterns between them were observed. In species with invasive placentas, such as the endotheliochorial placentas of Carnivora, some common Gr were detected among them, while others were species-specific. In species with hemochorial placenta, the same Gr are shared. Particularly, in the viscacha greater differences with species of the Hominidae and even Muridae families were observed. Nevertheless, greater similarities with other caviomorph rodents were detected. Placental glycotype of each species constitutes an excellent tool to achieve phylogenetic and evolutionary inferences among eutherians.

Placentation in the Mexican scincid lizard Plestiodon brevirostris (Squamata: Scincidae).

Viviparity is the reproductive pattern in which females gestate eggs within their reproductive tract to complete their development and give birth to live offspring. Within extant sauropsids, only the Squamata (e.g., snakes, lizards, and amphisbaenians) evolved viviparity, representing 20% of the existing species. The genus Plestiodon is represented by 43 species and is one of the most widely distributed genera of the Scincidae in Mexico. The goal of this research has been to determine the placental morphology and ontogeny during gestation in the lizard Plestiodon brevirostris. Specimens were dissected to obtain the embryonic chambers and the embryos were categorized to carry out the correlation between the development stage and the placenta development. The embryonic chambers were processed using the conventional histological technique for light microscopy. The identified embryonic stages were 4, 29, 34, 36, and 39. A thin eggshell surrounds the egg in early developmental stages; however, this structure is already absent in the embryonic hemisphere during the developmental stage 29. The results revealed that P. brevirostris is a lecithotrophic species, but a close maternal-fetal relationship is established by tissue apposition. Ontogenically, the placental types that form in the embryonic hemisphere are the chorioplacenta, choriovitelline placenta, and chorioallantoic placenta; whereas the omphaloplacenta is formed in the abembryonic hemisphere. The structure of the chorioallantoic placenta in P. brevirostris suggests that it may play a role during gas exchange between the mother and the embryo, due to the characteristics of the epithelia that comprise it. The structure of embryonic and maternal epithelia of the omphaloplacenta suggests a role in the absorption of the eggshell during gestation and possibly in the transport or diffusion of some nutrients. In general, it is evident that ontogeny and placental characteristics of P. brevirostris match those of other species of viviparous lecithotrophic scincids.

Influencia de la anastomosis de las arterias umbilicales (Hyrtl's) en la morfometría y eficiencia placentaria / Influence of the anastomosis of the umbilical arteries (Hyrtl's) on the morphometry and efficiency of the placenta

La anastomosis de Hyrtl's (AH), vaso único con amplia variabilidad anatómica, comunica las arterias umbilicales cerca de la inserción del cordón umbilical en las placentas humanas. El objetivo del presente trabajo fue determinar si existe relación entre las características morfométricas de la placenta y la presencia de anastomosis y analizar si esta tiene influencia en la eficiencia placentaria. Estudio descriptivo. Se analizaron 60 placentas provenientes de madres que aceptaron participar en la investigación, embarazo único, a término (entre 37,0 y 41,6 semanas), con edades entre 18 y 37 años, con al menos cuatro visitas a control prenatal, sin comorbilidades. Las características placentarias de peso, diámetros y grosor se tomaron en fresco. Una vez fijadas con formaldehido al 10 %, mediante disección se ubicó, clasificó y fotografió la anastomosis. El peso de la placenta fue 494,4 ± 87,1 gramos, el grosor central correspondió a 1,7 ± 0,4 cm, DM 19,9 ± 2,0 cm y Dm 18,4 ± 1,7 cm. La inserción de cordón predominante fue excéntrica (65 %) y la forma discoidea u ovalada (60 %). En 51 placentas se ubicó la presencia de anastomosis (85 %). En el grupo de placentas con presencia AH se encontró un peso placentario más bajo al compararlo con el grupo que no presentó AH, el resto de las características morfométricas de la placenta, incluido el tipo de inserción de cordón umbilical no presentaron relación con la anastomosis. La eficiencia placentaria expresada con la relación entre peso neonato/peso placenta presentó diferencias significativas en el grupo con presencia de anastomosis, con mayores valores comparados con el grupo sin anastomosis. La presencia de AH contribuye positivamente a la eficiencia placentaria. Sin embargo, el incremento del peso placentario puede ser un efecto compensador de la placenta y no siempre indica una mayor eficiencia funcional del órgano.

SUMMARY: Hyrtl's anastomosis (HA), a single vessel, with wide anatomical variability, communicates the umbilical arteries, near the insertion of the umbilical cord in human placentas. The objective of this study was to determine if there is a relationship between the morphometric characteristics of the placenta and the presence of the anastomosis and to analyze if this influences the placental efficiency. Descriptive study. We analyzed 60 placentas from mothers who agreed to participate in the study, single pregnancy, term (between 37.0 and 41.6 weeks), aged between 18 and 37 years with at least four visits to prenatal control, without comorbidities. The placental characteristics of weight, diameters and thickness were taken fresh. Once fixed with 10 % formaldehyde, the anastomosis was located, classified, and photographed by dissection. The weight of the placenta was 494.4 ± 87.1 g, the central thickness corresponded to 1.7 ± 0.4 cm, the MD 19.9 ± 2.0 cm and Dm 18.4 ± 1.7 cm: The predominant cord insertion was eccentric, with 65 % and the discoid or oval shape with 60 %. In 51 placentas the presence of anastomosis was found (85 %). In the group of placentas with AH presence, a lower placental weight was found when compared to the group that did not present AH, the rest of the morphometric characteristics of the placenta, including the type of umbilical cord insertion, were not related to the anastomosis. Placental efficiency expressed as the neonatal weight/placental weight ratio showed significant differences in the group with presence of anastomosis, with higher values compared to the group without anastomosis. The presence of HA contributes positively to placental efficiency. However, the increase in placental weight may be a compensatory effect of the placenta and does not always indicate a greater functional efficiency of the organ.

Mammalian Placentation: A Tribute to E.C. Amoroso's Contributions to Placenta Development.

Establishment of viviparity in mammals evolved through not only the long-term retainment of the fetus within the maternal uterus but differentiation and expansion of cell layers to form functional membranes to exchange O2/CO2 and nutrients between the placenta and maternal circulations. Development of a fetal placental vascular circulation to interact with the maternal uterus is critical to the survival of all species. However, the fascination with the mammalian placenta is the robust variation in types, form, attachment, invasiveness, structure, cell differentiation, endocrine function, and regulation of the maternal immune system. Despite the obvious role of the placenta to support fetal development, mammals have evolved multiple strategies to give live birth at term. The placenta and the maternal-fetal interface during pregnancy can be quite simple to very complex. Professor E.C. Amoroso contributed greatly to the study of comparative placentation in animals. His paper "Placentation" in Marshall's Physiology of Reproduction published in 1952 remains the standard for comparative placental anatomy today. The present volume on "Mammalian Placentation" brings together current reviews for leading experts to diversity of placentation in a number of mammalian species. Chapters will discuss viviparity, blastocyst formation, and placentation in the cow, pig, horse, mouse, dog, primate, human, elephant, and marsupials.

Toll-like receptor-4 null mutation causes fetal loss and fetal growth restriction associated with impaired maternal immune tolerance in mice.

Maternal immune adaptation to accommodate pregnancy depends on sufficient availability of regulatory T (Treg) cells to enable embryo implantation. Toll-like receptor 4 is implicated as a key upstream driver of a controlled inflammatory response, elicited by signals in male partner seminal fluid, to initiate expansion of the maternal Treg cell pool after mating. Here, we report that mice with null mutation in Tlr4 (Tlr4-/-) exhibit impaired reproductive outcomes after allogeneic mating, with reduced pregnancy rate, elevated mid-gestation fetal loss, and fetal growth restriction, compared to Tlr4+/+ wild-type controls. To investigate the effects of TLR4 deficiency on early events of maternal immune adaptation, TLR4-regulated cytokines and immune regulatory microRNAs were measured in the uterus at 8 h post-mating by qPCR, and Treg cells in uterus-draining lymph nodes were evaluated by flow cytometry on day 3.5 post-coitum. Ptgs2 encoding prostaglandin-endoperoxide synthase 2, cytokines Csf2, Il6, Lif, and Tnf, chemokines Ccl2, Cxcl1, Cxcl2, and Cxcl10, and microRNAs miR-155, miR-146a, and miR-223 were induced by mating in wild-type mice, but not, or to a lesser extent, in Tlr4-/- mice. CD4+ T cells were expanded after mating in Tlr4+/+ but not Tlr4-/- mice, with failure to expand peripheral CD25+FOXP3+ NRP1- or thymic CD25+FOXP3+ NRP1+ Treg cell populations, and fewer Treg cells expressed Ki67 proliferation marker and suppressive function marker CTLA4. We conclude that TLR4 is an essential mediator of the inflammation-like response in the pre-implantation uterus that induces generation of Treg cells to support robust pregnancy tolerance and ensure optimal fetal growth and survival.

Methodology for Biometrical Analysis of the Placenta: Feasibility and Reproducibility.

The role of a healthy placenta as the interface between mother and fetus, which regulates the intrauterine environment and affects fetal and pregnancy outcomes, points to placental examination as a potentially useful diagnostic tool. Placental macroscopic and microscopic patterns are routinely evaluated when pregnancy complications occur. Moreover, placental measures particularly the ratio between fetal and placental weight have been reported to correlate with maternal characteristics, such as BMI as well as with birth-weight and fetal gender. Our pilot study evaluates the feasibility of the placental measures' reproducibility intra-operators. We enrolled 50 consecutive singleton pregnancies including physiological pregnancies and any pre-existing maternal disease or maternal and fetal complication. We conducted a macroscopic analysis of fetal adnexa with four different operators assessing pathological findings or other abnormalities. Intra-class correlation coefficient (ICC) and Cohen and Fleiss kappa coefficient were used to assess the degree of consistency between operators. The results of our study show that the placental morphometric analysis is a reproducible method.

Gross and histological findings in the canine placenta and amnion at term: What's normal, abnormal or pathological?

The canine placenta is an underexamined organ. Placental abnormalities can affect foetus development and may be responsible for a low weight of the infant at birth; however, knowledge on their clinical significance in the canine species is limited. We aimed to describe macroscopic and microscopic findings in the canine placenta and amnion at term in clinically uncomplicated pregnancies and to evaluate their relationship with birth weight of healthy puppies. During natural delivery or C-section, the birth weight of 82 puppies was recorded, 72 placentas and 66 amnions were recovered. The foetal and maternal surfaces of the placental girdle, marginal haematoma and amnion were evaluated. Each gross finding was recorded, morphometrically assessed and sampled for histological diagnosis. Furthermore, specimens of placenta and amnion were collected from representative areas and microscopic deviations from normal structure were evaluated in haematoxylin and eosin sections. Gross examination revealed 'abnormalities' in the 75.4% of the collected placentas. Necrosis was the gross change most commonly observed in the placental girdle (72.5%). Congestion (17.4%) and clotted blood/fibrinoid material (2.9%) were also observed. No gross changes of either the marginal haematoma or the amnion were recorded. Histologically, placental girdle showed necrosis (62.3%), mineralization (52.2%), congestion (36.2%) and neutrophilic infiltration (27.5%). Marginal haematoma exhibited mineralization (11.6%) and neutrophils (29%), while necrotic foci were rarely observed (4.3%). In the amnion, the most frequent alteration observed was hypertrophy of the epithelium (35.9%) followed by oedema (31.2%), mineralized foci (28.1%), fibrosis (23.4%), congestion (15.6%) and more rarely neutrophils (12.5%). Puppies' birth weight was not statistically affected by either gross or histological abnormalities. Our study revealed that macroscopic and microscopic 'abnormalities' of the placenta and amnion may be common in uncomplicated pregnancies at term; however, no implications on puppies' birth weight were observed. Deviations from 'normal' morphology of canine foetal adnexa warrant further investigation to assess their clinical implications if present.

Effects of maternal nutrient restriction during the periconceptional period on placental development in the mouse.

Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic disease risks during adulthood. The placenta is responsible for transport of nutrients from the maternal to fetal circulation, and the efficiency with which it does so can be adjusted to the maternal nutrient supply. There is evidence that placental adaptations to nutrient restriction in early pregnancy may be retained even when adequate nutrition is restored later in pregnancy, leading to a potential mismatch between placental efficiency and maternal nutrient supplies. However, in the mouse, 50% caloric restriction from days 1.5-11.5 of gestation, while temporarily altering placental structure and gene expression, had no significant effect on day 18.5. The periconceptional period, during which oocyte maturation, fertilization, and preimplantation development occur may be especially critical in creating lasting impact on the placenta. Here, mice were subjected to 50% caloric restriction from 3 weeks prior to pregnancy through d11.5, and then placental structure, the expression of key nutrient transporters, and global DNA methylation levels were examined at gestation d18.5. Prior exposure to caloric restriction increased maternal blood space area, but decreased expression of the key System A amino acid transporter Slc38a4 at d18.5. Neither placental and fetal weights, nor placental DNA methylation levels were affected. Thus, total caloric restriction beginning in the periconceptional period does have a lasting impact on placental development in the mouse, but without changing placental efficiency.

An investigation into uterine capacity based on litter and placental characteristics in two sow lines with different prolificacy (Danish Landrace x Danish Yorkshire versus German Saddleback).

Litter size in modern so called hyperprolific pig (Sus scrofa Linnaeus) breeds such as of crossbred Danish Landrace x Danish Yorkshire (LY/YL) sows increased remarkably over recent years, however, commonly associated with reduced piglet birth weight and higher within litter birth weight variability likely due to a limited uterine capacity. Since investigation into this issue is patchy, the aim of this study was to investigate uterine capacity based on litter and placental characteristics in two sow lines with different prolificacy, that is crossbred Danish genetic (Danish Landrace x Danish Yorkshire; DG; n = 14) and purebred German Saddleback (GS) sows (n = 12). Parameters recorded were litter size, piglet birth weight and vitality, placental weight and surface area as well as placental vascularization. Litters of DG were on average larger than of GS (p < .001). Piglets of DG weighed on average less than GS (p < .001) and were less vital (p < .001-.142). Increasing litter size was associated with reduced piglet birth weight and increased within litter birth weight variability in GS, but not in DG. DG had on average a lower placental weight (p < .001) and smaller placentae (p < .001) than GS, but the placenta was on average more efficient than of GS (based on the quotient of piglet and corresponding placental weight; p < .001). Vascularization of placentae was on average not or only slightly different between breeds (p < .05 - .982). Remarkably, however, vascularization of the lateral and apical chorionic epithelium of the chorionic ridges as the immediate foetal/maternal interface was on average slightly higher in DG than GS (p < .05-.111). Results thus demonstrate that uterine capacity based on litter and placental characteristics is higher in DG than GS sows.

The Effect of Maternal Physical Activity and Gestational Weight Gain on Placental Efficiency.

INTRODUCTION: Adherence to physical activity (PA) and gestational weight gain (GWG) recommendations during pregnancy has been shown to improve maternal and fetal health outcomes, including reducing the risk for chronic diseases. Limited research has evaluated the effect of meeting PA in combination with GWG recommendations on placental efficiency (Pl-E), a surrogate marker of the placenta's ability to exchange nutrients and gas based on surface area. The purpose of this study was to measure and compare Pl-E based on meeting PA and GWG recommendations. METHOD: Healthy pregnant women (n = 61) wore accelerometers in their second and third trimesters to objectively measure PA. Women were classified as active or inactive at each time point based on meeting the 2019 Canadian prenatal PA guidelines. Total GWG was calculated as weight measured in the third trimester minus self-reported prepregnancy weight, and were categorized as insufficient (n = 19), adequate (n = 22), and excessive (n = 20) according to the 2009 Institute of Medicine guidelines. Placental weight (PW) and birth weight (BW) were measured within 30 min of delivery and 24-48 h postdelivery, respectively. Pl-E was determined in three ways: BW:PW ratio, residual BW, and measured BW, with a higher value indicating better Pl-E. Pl-E was compared by PA and GWG status using a two-way ANOVA. RESULTS: No differences were found in the BW:PW ratio or residual BW corresponding to PA and GWG status. Measured BW was significantly higher in newborns of women who gained weight excessively compared with those who gained insufficient weight (P < 0.05). CONCLUSION: These findings suggest that prenatal PA does not compromise Pl-E; however, further research is required to evaluate the potential mechanistic benefits of meeting PA and GWG guidelines on the placenta.

Longer distance between umbilical cord insertions is associated with spontaneous twin anemia polycythemia sequence.

INTRODUCTION: The aim of the study was to investigate the placental characteristics in spontaneous twin anemia polycythemia sequence. MATERIAL AND METHODS: A retrospective case-control study of spontaneous twin anemia polycythemia sequence, twin-to-twin transfusion syndrome and normal monochorionic diamniotic twin pregnancies was performed. The primary outcome was placental characteristics. RESULTS: The prevalence of artery-artery anastomoses in spontaneous twin anemia polycythemia sequence and twin-to-twin transfusion syndrome groups was significantly lower than in the normal monochorionic diamniotic twin group (40.0% vs 33.3% vs 88.8%, respectively, P < .001). The total number of vascular anastomoses in the spontaneous twin anemia polycythemia sequence group (with range given in parentheses) was significantly lower than in the two control groups (3 [1-6] vs 5 [1-14] vs 6 [1-20], P = .001/<.001/.794). The number of artery-vein anastomoses in the spontaneous twin anemia polycythemia sequence was significantly lower than in the two control groups (2 [1-5] vs 4 [1-13] vs 5 [1-19], P = .011/.001/1.000). The total diameter of all vascular anastomoses was significantly smaller in the spontaneous twin anemia polycythemia sequence than in the two control groups (0.9 mm [0.3-4.7] vs 5.2 mm [0.8-24.6] vs 7.3 mm [1.0-25.1], P < .001/<.001/.104), as was the total diameter of artery-to-artery anastomoses (0.5 mm [0.3-1.3] vs 2.0 mm [0.5-11.8] vs 2.3 mm [0.7-9.7], P = .003/<.001/1.000) and the total diameter of artery-to-vein anastomoses (0.8 mm [0.3-2.1] vs 4.6 mm [0.8-15.3] vs 4.0 mm [0.2-21.8], P < .001/<.001/1.000). The ratio between the distance of the two umbilical cords insertion points and the placental maximum diameter in the spontaneous twin anemia polycythemia sequence group was significantly larger than in the two control groups (0.78 [0.49-0.99] vs 0.64 [0.32-1.00] vs 0.55 [0.05-1.00], P = .033/<.001/.138). CONCLUSIONS: In spontaneous twin anemia polycythemia sequence placentas, the number of superficial vascular anastomoses is lower, their diameter is smaller and the distance between the two umbilical cord insertion points is longer.

Importancia social del estudio morfométrico en placentas procedentes de embarazos gemelares / Social importance of the morphometric study in placentas from twin pregnancies

Se fundamenta la necesidad de la investigación científica para el estudio morfométrico en placentas procedentes de embarazos gemelares, como aproximación a la correlación entre el patrón morfométrico, la corionicidad y el bienestar fetal y neonatal, en tanto criterios básico/clínicos a tomar en cuenta para perfeccionar las acciones del programa nacional de salud sexual y reproductiva en Cuba. Se destaca la importancia social de un diseño de investigación en este campo, al constatar las carencias epistémicas desde una búsqueda sistematizada de información bibliográfica sobre el tema(AU)

The need for scientific research for the morphometric study in placentas from twin pregnancies is founded, as an approximation to the correlation between the morphometric pattern, chorionicity and fetal and neonatal well-being, as basic/clinical criteria to be taken into account to improve the actions of the national sexual and reproductive health program in Cuba. The social importance of a research design in this field is highlighted, when verifying the epistemic deficiencies from a systematized search of bibliographic information on the subject(EU)

Resilience to drought in semi-desert sheep: Effects of water restriction during pregnancy on placental efficiency in the Awassi breed.

Assessing the resilience of Awassi sheep to water shortages during pregnancy, thereby investigating the effects of water scarcity on gestation efficiency in animals, could provide valuable and pertinent insight into future scenarios posed by climate change risks. In this study, 40 pregnant Awassi ewes randomly allocated to free watering group (C, n = 20) received water ad libitum and the water restricted group (WR) received 50% less water than the amount provided to group C. Water restriction decreased (p < .05) lambs' birth weights, placental weights (PWs), and cotyledon numbers (CNs). Placental efficiency (PE) and cotyledon efficiency (CE) were significantly higher in the WR group (p < .05). A marked difference in cotyledon weight - an increase of 12.1% - was recorded in the C group. The body weights of the pregnant ewes in the WR group decreased significantly (p < .05) by 22% during pregnancy. Significant increases (p < .05) in plasma ADH, cholesterol, Cl- , and Na+ levels were observed in the WR group ewes, indicating intense dehydration. We conclude that the Awassi breed of sheep can endure 50% water restriction during pregnancy and maintain successful parturition, a key outcome for sustainability.

The unique applicability of the human placenta to the Adverse Outcome Pathway (AOP) concept: the placenta provides fundamental insights into human organ functions at multiple levels of biological organization.

Despite the short lifespan of the human placenta, the proper formation and function of the organ is of crucial importance for fetal development. Placental dysfunction increases the risk of complications for mother and child during pregnancy and childbirth and beyond as it predisposes to fetal programming. The placenta is an upstream organ of the fetus. It performs the functions of fetal lungs, liver, intestines, kidneys and glands as long as these organs are not fully functional. Furthermore, it is the only human organ that is non-invasively available either after elective abortion or after birth. This is a crucial point given that the conceptual framework of Adverse Outcome Pathway (AOP) requires data on organ function. In vitro and ex vivo placental studies, combined with epidemiological and clinical data on pregnant women, newborns, and infants can uniquely cover all levels of information needed to develop new AOPs and complement existing AOPs related to reproductive toxicity and beyond. To stimulate further research in this area and to support researchers in future studies dealing with the development of AOPs related to the placenta, this review first gives a brief description of placental structure, placental development and relevant pregnancy diseases. The state of knowledge about the available placental models, their particularities and limitations are briefly discussed. Finally, the use of placental research for the development of AOPs is presented with an illustrative example.

Characteristics of the equine placenta at first trimester / Características de la placenta equina en el primer trimestre

The equine placenta is a simple apposition of fetal and maternal tissues, becoming more complex with the formation of microcotyledons around days 75 and 100 of gestation. The present study aimed to describe the gross and microscopic morphology of early equine placenta. Embryonic/fetal membranes from thirty-seven mares were submitted to macroscopic description, light, scanning and transmission microscopy. Overall the gross characteristics of membranes were similar with already described for older stages. However, transmission electron microscopy evidenced high metabolic rate in chorion and allantois, and high secretion profile in amnion and even higher in yolk sac. Gene ontologies enrichment, using published data, pointed several common ontologies in allantoic and amniotic fluids, related to oxygen and iron transport, extracellular space and high-density lipoprotein receptor binding. Overall, the morphological and ontology enrichment could indicate allantois and amnion crosstalk.

La placenta equina es una simple aposición de tejidos fetales y maternos, que se vuelve más compleja con la formación de microcotiledones alrededor de los días 75 y 100 de gestación. El presente estudio tuvo como objetivo describir la morfología macroscópica y microscópica de la placenta equina temprana. Las membranas embrionarias / fetales de treinta y siete yeguas fueron sometidas a descripción macroscópica, luz, escaneo y microscopía de transmisión. En general, las características generales de las membranas fueron similares a las ya descritas para las etapas más antiguas. Sin embargo, la microscopía electrónica de transmisión mostró una alta tasa metabólica en corion y alantoides, y un alto perfil de secreción en amnios e incluso mayor en el saco vitelino. El enriquecimiento de ontologías génicas, utilizando datos publicados, señaló varias ontologías comunes en fluidos alantoideos y amnióticos, relacionados con el transporte de oxígeno y hierro, espacio extracelular y unión a receptores de lipoproteínas de alta densidad. En general, el enriquecimiento morfológico y ontológico podría indicar alantoides y diafonía de amnios.

An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD.

BACKGROUND: Individuals exposed to gestational stressors such as alcohol exhibit a spectrum of growth patterns, suggesting individualized responses to the stressors. We hypothesized that intrauterine growth responses to gestational alcohol are modified not only by the stressor's severity but by fetal sex and the placenta's adaptive capacity. METHODS: Pregnant C57BL/6J mice were assigned to one of three groups. Group 1 consumed a normal protein diet (18% protein by weight) and received 4.5 g alcohol/kg body weight (NP-Alc-8) or isocaloric maltodextrin (NP-MD-8) daily from embryonic day (E) 8.5-E17.5. Group 2 consumed the same diet but received alcohol (NP-Alc-13) or maltodextrin (NP-MD-13) daily from E13.5-E17.5. Group 3 consumed the same diet but containing a lower protein content (12% protein by weight) from E0.5 and also received alcohol (LP-Alc-8) or maltodextrin (LP-MD-8) daily from E8.5-E17.5. Maternal, placental, and fetal outcomes were assessed on E17.5 using 2-way ANOVA or mixed linear model. RESULTS: We found that intrauterine growth differed in the alcohol-exposed fetuses depending on sex and insult severity. Both NP-Alc-8 (vs. NP-MD-8) males and females had lower body weight and asymmetrical growth, but only NP-Alc-8 females had lower placental weight (P < 0.05). NP-Alc-13 (vs. NP-MD-13) females, but not their male littermates, had lower body weight (P = 0.019). Alcohol exposure beginning from E8.5 (vs. E13.5) decreased the ratio of fetal liver-to-body weight and increased the ratio of fetal brain-to-liver weight in both sexes (P < 0.05). LP-Alc-8 (vs. NP-MD-8) group had smaller litter size (P = 0.048), but the survivors had normal placental and body weight at E17.5. Nevertheless, LP-Alc-8 fetuses still showed asymmetrical growth. Correlation analyses reveal a relationship between litter size and placental outcomes, which were related to fetal outcomes in a sex-dependent manner, suggesting that the placenta may mediate the consequence of LP-Alc-altered litter size on fetal development. CONCLUSIONS: Our data indicate that the placenta is strongly involved in the fetal stress response and adapts in a sex-dependent fashion to support fetal development under the alcohol stressor. These variables may further influence the spectrum of intrauterine growth outcomes observed in those diagnosed with fetal alcohol spectrum disorder.

Absence of lymphatic vessels in term placenta.

BACKGROUND: There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2-40 have been found, although PROX1 has not been detected. The most reliable marker for LECs is the double staining for CD31 and PROX1, which has not been performed yet. METHODS: We studied three term placentas and dissected them into three areas: i.) basal plate area, ii.) intermediate area, and iii.) chorionic plate area. We used immunofluorescence single and double staining with antibodies against CD31, PROX1, LYVE-1, VEGFR-3, D2-40/PDPN, CD34, CCBE-1, and vimentin, as well as nested PCR, qPCR, Western blot and transmission electron microscopy (TEM). RESULTS: At TEM level we observed structures that have previously mistakenly been interpreted as lymphatics, however, we did not find any CD31/PROX1 double-positive cells in placenta. Absence of PROX1 was also noted by nested PCR, qPCR and Western blot. Also, LEC marker VEGFR-3 was expressed only in a small number of scattered leukocytes but was absent from vessels. The LEC marker D2-40/PDPN was expressed in most stromal cells, and the LEC marker LYVE-1 was found in a considerable number of stromal cells, but not in endothelial cells, which were positive for CD31, CD34, CCBE-1 and vimentin. Additionally, vimentin was found in stromal cells. CONCLUSIONS: Our studies clearly show absence of lymphatics in term placenta. We also show that the functional area of the mother's endometrium is not penetrated by lymphatics in term pregnancy.

Timing of exposure to gonadotropins has differential effects on the conceptus: evidence from a mouse model†.

Superovulation with gonadotropins alters the hormonal milieu during early embryo development and placentation, and may be responsible for fetal and placental changes observed after in vitro fertilization (IVF). We hypothesized that superovulation has differential effects depending on timing of exposure. To test our hypothesis, we isolated the effect of superovulation on pre- and peri-implantation mouse embryos. Blastocysts were obtained from either natural mating or following superovulation and mating, and were transferred into naturally mated or superovulated pseudopregnant recipient mice. Fetal weight was significantly lower after peri-implantation exposure to superovulation, regardless of preimplantation exposure (p = 0.006). Placentas derived from blastocysts exposed to superovulation pre- and peri-implantation were larger than placentas derived from natural blastocysts that are transferred into a natural or superovulated environment (p < 0.05). Fetal-to-placental weight ratio decreased following superovulation during the pre- or peri-implantation period (p = 0.05, 0.01, respectively) and these effects were additive. Peg3 DNA methylation levels were decreased in placentas derived from exposure to superovulation both pre- and peri-implantation compared with unexposed embryos and exposure of the preimplantation embryo only. Through RNA sequencing on placental tissue, changes were identified in genes involved in immune system regulation, specifically interferon signaling, which has been previously implicated in implantation and maintenance of early pregnancy in mice. Overall, we found that the timing of exposure to gonadotropin stimulation can have differential effects on fetal and placental growth. These findings could impact clinical practice and underscores the importance of dissecting the role of procedures utilized during IVF on pregnancy complications.