Genomics, the diversification of mammals, and the evolution of placentation.

When and why did variations in placental structure and function evolve? Such questions cannot be addressed without a reliable version of mammalian phylogeny. Twenty-five years ago, the mammalian tree was reshaped by molecular phylogenetics. Soon it was shown, in contrast to prevailing theories, that the common ancestor of placental mammals had invasive placentation. Subsequently, evolution of many other features of extraembryonic membranes was addressed. This endeavour stimulated research to fill gaps in our knowledge of placental morphology. Last year the mammalian tree was again revised based on a large set of genomic data. With that in mind, this review provides an update on placentation in the nineteen orders of placental mammals, incorporating much recent data. The principal features such as shape, interdigitation, the interhaemal barrier and the yolk sac are summarized in synoptic tables. The evolution of placental traits and its timing is then explored by reference to the revised mammalian tree. Examples are the early appearance of epitheliochorial placentation in the common ancestor of artiodactyls, perissodactyls, pangolins and carnivores (with reversion to invasive forms in the latter) and later refinements such as the binucleate trophoblast cells and placentomes of ruminants. In primates, the intervillous space gradually evolved from the more basic labyrinth whereas trophoblast invasion of the decidua was a late development in humans and great apes. Only seldom can we glimpse the "why" of placental evolution. The best examples concern placental hormones, including some striking examples of convergent evolution such as the chorionic gonadotropins of primates and equids. In concluding, I review current ideas about what drives placental evolution and identify significant gaps in our knowledge of placentation, including several relevant to the evolution of placentation in primates.

Association between trimester-specific prenatal air pollution exposure and placental weight of twins.

INTRODUCTION: This study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. METHODS: Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. RESULTS: In the third trimester, for each 10 µm/m3 increase in PM10 or NO2 placental weight decreased -19.7 g (95%-C.I. -35.1; -4.3) and -17.7 g (95%-C.I. -30.4; -0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). DISCUSSION: The association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.

Evaluation of embryo-foetal biometry and its correlation with parturition date in Toy Poodle bitches.

Estimating the parturition date in dogs is challenging due to their reproductive peculiarities that. Ultrasonographic examination serves as a tool for studying embryo/foetal biometry and estimating the time of parturition by measuring foetal and extra-foetal structures. However, due to reproductive differences among various dog breeds, such estimates may have a non-significant pattern, representing inaccuracies in the estimated date of birth. This study aimed to monitor pregnant Toy Poodle bitches and establish relationships between ultrasonographically measured foetal and extra-foetal dimensions and the remaining time until parturition. Eighteen pregnant Toy Poodle bitches were subjected to weekly ultrasonographic evaluations and measurements of the inner chorionic cavity diameter, craniocaudal length (CCL), biparietal diameter (BPD), diameter of the deep portion of diencephalo-telencephalic vesicle (DPTV), abdominal diameter, thorax diameter (TXD), placental thickness and the renal diameter (REND). These parameters were retrospectively correlated with the date of parturition and linear regressions were established between gestational measurements and days before parturition (DBP). All analyses were conducted using the Statistical Package for Social Sciences (IBM® SPSS®) program at a 5% significance level. The foetal measurements that showed a high correlation (r) and reliability (R2) with DBP were BPD [(DBP = [15.538 × BPD] - 39.756), r = .97 and R2 = .93], TXD [(DBP = [8.933 × TXD] - 32.487), r = .94 and R2 = .89], DPTV [(DBP = [34.580 × DPTV] - 39.403), r = .93 and R2 = .86] and REND [(DBP = [13.735 × REND] - 28.937), r = .91 and R2 = .82]. This statistically validates the application of these specific formulas to estimate the parturition date in Toy Poodle bitches.

Assessment of an AI-based tool for population-wide collection of placental morphological data.

OBJECTIVES: Automated placental assessment could allow accurate and timely morphological/pathological measurements at scale. We undertook a pilot study using an artificial intelligence-based assessment system (AI-PLAX) to ascertain the potential of a state-wide rollout as part of Generation Victoria, assessing the impact of time post-delivery, user, and technology used for image capture, on a range of derived placental data. STUDY DESIGN: Ten placentas were imaged by three different users and imaging technologies (iPad, iPhone, Samsung) at (0 h), 24 h, and 48 h post-delivery. Using AI-PLAX, disc size (short and long length, perimeter, area), shape (normal, abnormal), cord insertion type (central, eccentric), cord coiling, abruption (retroplacental hematoma), and meconium staining were determined. RESULTS: When analysing the maternal surface of the placenta, time in cold storage post-delivery had modest effects on placental dimensions, with decreases in the short length (24-48 h: -3.7 %), disc area (0-24 h: 4.7 % and 0-48 h: -7.4 %), and perimeter (0-48 h: -3.8 %) observed. There was marginal impact on placental dimensions when the placenta was imaged by different users, including long length (+1.9 %), disc area (+2.9 %), and perimeter (+2.0 %). Measures of placental size were not impacted by the type of technology used to capture the images. When analysing the fetal surface of the placenta, more variance in placental size measures were observed between users. Abruption detection was not affected by any parameter. Time between delivery and imaging impacted apparent meconium staining - likely reflecting changes in fetal surface colour over time. Meconium staining was not affected by technology or user. CONCLUSIONS: This study supports the feasibility of the collection of placenta images for later morphological analysis by AI-PLAX, with measures obtained minimally influenced by time in cold storage, user imaging the placenta, or technology to capture the images.

Sociodemographic factor associations with maternal and placental outcomes: A cluster and partial least squares regression analysis.

INTRODUCTION: Maternal social disadvantage adversely affects maternal and offspring health, with limited research on placental outcomes. Therefore, we examined maternal sociodemographic factor associations with placental and birth outcomes in general (Lifeways Cross-Generation Cohort) and at-risk (PEARS Study of mothers with overweight or obesity) populations of pregnant women. METHODS: TwoStep cluster analysis profiled Lifeways mothers (n = 250) based on their age, parity, marital status, household income, private healthcare insurance, homeowner status, and education. Differences in placental and birth outcomes (untrimmed placental weight (PW), birthweight (BW) and BW:PW ratio) between clusters were assessed using one-way ANOVA and chi-square tests. Partial least squares regression analysed individual effects of sociodemographic factors on placental and birth outcomes in Lifeways and PEARS mothers (n = 461). RESULTS: Clusters were classified as "Married Homeowners" (n = 140, 56 %), "Highest Income" (n = 58, 23.2 %) and "Renters" (n = 52, 20.8 %) in the Lifeways Cohort. Renters were younger, more likely to smoke, have a means-tested medical card and more pro-inflammatory diets compared to other clusters (p < 0.01). Compared to Married Homeowners, renters' offspring had lower BW (-259.26 g, p < 0.01), shorter birth length (-1.31 cm, p < 0.01) and smaller head circumference (-0.59 cm, p = 0.02). PLS regression analyses identified nulliparity as having the greatest negative effect on PW (Lifeways and PEARS) while being a homeowner had the greatest positive effect on PW (Lifeways). CONCLUSION: Certain combinations of sociodemographic factors (particularly homeownership) were associated with less favourable lifestyle factors, and with birth, but not placental outcomes. When explored individually, parity contributed to the prediction of placental and birth outcomes in both cohorts of pregnant women.

Exercise FITT-V during pregnancy: Association with birth outcomes.

BACKGROUND: Prenatal exercise improves birth outcomes, but research into exercise dose-response effects is limited. METHODS: This study is a retrospective, secondary analysis of pooled data from three blinded, prospective, randomized controlled trials. Prenatal exercise frequency, intensity, type, time, and volume (FITT-V) were assessed in supervised sessions throughout pregnancy. Gestational age (GA), neonatal resting heart rate (rHR), morphometrics (body circumferences, weight-to-length and ponderal index) Apgar and reflex scores, and placental measures were obtained at birth. Stepwise regressions and Pearson correlations determined associations between FITT-V and birth outcomes. RESULTS: Prenatal exercise frequency reduces ponderal index (R2 = 0.15, F = 2.76, p = .05) and increased total number of reflexes present at birth (R2 = 0.24, F = 7.89, p < .001), while exercise intensity was related to greater gestational age and birth length (R2 = 0.08, F = 3.14; R2 = 0.12, F = 3.86, respectively; both p = .04); exercise weekly volume was associated with shorter hospital stay (R2 = 0.24, F = 4.73, p = .01). Furthermore, exercise type was associated with placenta size (R2 = 0.47, F = 3.51, p = .01). CONCLUSIONS: Prenatal exercise is positively related to birth and placental outcomes in a dose-dependent manner.

Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

Presence and Size of Placental Lakes on 20-Week Fetal Anatomy Ultrasound and Obstetrical Outcomes.

Our objective was to determine if placental lake presence or size is associated with adverse pregnancy outcomes. This was a retrospective cohort of patients who had fetal anatomy ultrasounds at 18-22 weeks and delivered between 2018 and 2022. Placental lakes were classified as small (>2.0 to 3.9 cm) or large (≥4 cm). Multiple gestations, placenta previas, and placenta accretas were excluded. Outcomes included low birthweight, cesarean delivery, primary cesarean for non-reassuring fetal heart tracing, fetal growth restriction, preterm birth, and severe preeclampsia. A total of 1052 patients were included; 294 had placental lakes (204 small, 90 large). No differences in pregnancy outcomes were observed.

Paternal age and first trimester placental size and growth: The Rotterdam Periconceptional Cohort.

INTRODUCTION: Despite a noticeable trend of delayed fatherhood, less is known about the impact of paternal age on the paternally programmed placenta. We hypothesize that paternal aging affects seminal quality and as such induces ageing-related epigenetic alterations that influence placental growth. Our main aim is to investigate associations between paternal age and first trimester (vascular) placental growth trajectories. METHODS: Pregnant women were enrolled before 10 weeks of gestation in the Rotterdam Periconceptional Cohort (Predict study). Placental volumes (PV) and utero-placental vascular volumes (uPVV) were measured at 7, 9, and 11 weeks gestation. Associations between paternal age and PV and uPVV were investigated using linear mixed models and the maximum likelihood ratio test to test non-linear relationships. We adjusted for gestational age, fetal sex, parental smoking and maternal age, BMI, education and parity, and stratified for conception mode. RESULTS: From 808 pregnancies we obtained 1313 PV and from 183 pregnancies 345 uPVV measurements. We show no associations between paternal age and PV (p = 0.934) and uPVV (p = 0.489) in our total population or in pregnancies conceived naturally (PV p = 0.166; uPVV p = 0.446) and after IVF/ICSI (PV p = 0.909; uPVV p = 0.749). For example, PV was 0.9% smaller (95% CI -5.7%-7.1%) in fathers aged 40 compared to 30 years old at 9 weeks gestation in the total study population. DISCUSSION: We are not demonstrating a significant impact of paternal age on first trimester placental growth in a tertiary care population. Given the trend of increasing paternal age, our study should be repeated in the general population.

Maternal physical activity and sitting time and its association with placental morphology and blood flow during gestation: Findings from the Queensland Family Cohort study.

OBJECTIVES: Antenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation. DESIGN: Prospective cohort study. METHODS: Pregnant women in the Queensland Family Cohort study self-reported physical activity at 24 and 36 weeks of gestation (n = 203) and were categorised into physical activity volume groups of nil-low (0-<500 metabolic equivalent of task·minutes/week), moderate (500-<1000 metabolic equivalent of task·minutes/week), or high-volume activity (≥1000 metabolic equivalent of task·minutes/week). Participants reported average daily sitting time, whereby excessive sitting time was considered as ≥8h/day. Placental stiffness, thickness, and uteroplacental blood flow resistance were measured by ultrasound imaging at each timepoint. RESULTS: Physical activity volume was not associated with changes to placental morphometrics or uteroplacental blood flow resistance at 24 or 36 weeks of gestation. Excessive sitting time at 36 weeks was associated with greater placental stiffness (p = 0.046), and a lower umbilical artery pulsatility index (p = 0.001). CONCLUSIONS: Placental tissue stiffness and umbilical artery resistance were altered in late gestation with higher maternal sitting time but not with physical activity volume. Overall, excessive sitting time may be a risk for suboptimal placental function and could be an important focus for antenatal care.

Impact of birth weight to placental weight ratio and other perinatal risk factors on left ventricular dimensions in newborns: a prospective cohort analysis.

OBJECTIVES: To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. METHODS: A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. RESULTS: We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03-0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=-0.07, p=0.039), LV mass (estimate=-0.11, p=0.024), and LV mass/volume (estimate=-0.55, p=0.005). CONCLUSIONS: This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies.

Association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from the 2010/2011 BRISA birth cohort.

OBJECTIVE: To study the association between placental efficiency with anthropometry and nutritional phenotypes in full-term newborns from a birth cohort. METHOD: This was a secondary cross-sectional analysis of data obtained in a cohort study (Brazilian RibeirãoPreto and São Luís Birth Cohort Studies - BRISA), whose deliveries were performed between 2010 and 2011. Standardized questionnaires were applied to mothers, and placentas and newborns were evaluated shortly after delivery. Placental efficiency was assessed using the ratio between birth weight and placental weight (BW/PW ratio); values below the lower quartile (25th percentile for gestational age) were considered to have low placental efficiency. Newborn phenotypes were small and large for gestational age, stunted and wasted, evaluated using the INTERGROWTH-21 growth standard. To identify the confounding variables theoretical model was constructed using Directed Acyclic Graphs, and unadjusted and adjusted logistic regression were performed. Placental measurements were obtained blindly from pregnancy and delivery data. RESULTS: 723 mother-placenta-child triads were studied. 3.2 % of newborns were small-for-gestational-age (SGA), 6.5 %large-for-gestational-age (LGA), 5.7 %had stunting, and 0.27 % wasting. A significantly higher risk was found between low placental efficiency and SGA (OR 2.82;95 % CI 1.05-7.57), stunting (OR 2.23; 95 % CI 1.07-4.65), and wasting (OR 8.22; 95 % CI 1.96-34.37). No relationship was found between LGA and placental efficiency. CONCLUSIONS: Low placental efficiency was associated with increased risk for small-for-gestational-age, stunting, and wasting. Placental morphometry can provide valuable information on intrauterine conditions and neonatal health, helping to identify newborns at higher risk of future comorbidities.

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.