Human fetal Doppler ultrasound and invasive blood gas measurements obtained by cordocentesis or at the time of delivery reveal similarities with sheep (an extensively used model for human fetal cardiovascular physiology). r Oxygen saturation (SO 2) measurements in human fetuses have been limited to the umbilical and scalp vessels, providing little information about normal regional SO 2 differences in the fetus. r Blood T2 MRI relaxometry presents a non-invasive measure of SO 2 in the major fetal vessels. r This study presents the first in vivo validation of fetal vessel T2 oximetry against the in vitro T2-SO 2 relationship using catheterized sheep fetuses and compares the normal SO 2 in the major vessels between the human and sheep fetal circulations. r Human fetal vessel SO 2 by T2 MRI confirms many similarities with the sheep fetal circulation and is able to demonstrate regional differences in SO 2 ; in particular the significantly higher SO 2 in the left versus right heart.

The endocervix in the female reproductive tract (FRT) is susceptible to sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Endocervical epithelial cells in vivo make innate immune mediators that likely aid in the protection from these pathogens. In vitro studies to investigate the innate epithelial cell immune response to endocervical pathogens have been hindered by the paucity of human endocervix-derived epithelial cell lines that display the differentiation proteins and functional characteristics of their site of origin. We have established an immortalized epithelial cell line (A2EN) derived from an endocervical tissue explant that can be polarized to exhibit distinct apical and basolateral membrane domains. Polarized A2EN cells secrete mucus at their apical surface, and express MUC5B, a mucin specific to the endocervix. Polarized A2EN cells also express hormone receptors that respond appropriately to female steroid hormones. Polarized A2EN cells can be stimulated with the toll-like receptor 3 agonist, polyI:C, to express anti-microbial peptides (AMPs) as well as pro-inflammatory cytokines and chemokines. Cytokines and chemokines are also differentially secreted depending on the hormone milieu in which the cells are exposed. We conclude that polarized A2EN cells maintain distinctive phenotypic and functional characteristics of the epithelial cells found in the endocervix and, hence, could provide a useful, new in vitro model system for investigations on the role of endogenous and exogenous factors that regulate endocervical epithelial cell immunity including studies on sexually transmitted infections and topical microbicides.

Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low‐resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way. Preterm Yucatan miniature piglets are similar in size to extremely preterm human infants and share similar umbilical cord anatomy, raising the possibility to serve as a good model to investigate the AP. To characterize fetal cardiovascular physiology, the carotid artery (n = 24) was cannulated in utero and umbilical vein (UV) and umbilical artery were sampled. Fetal UV flow was measured by MRI (n = 16). Piglets were delivered at 98 ± 4 days gestation (term = 115 days), cannulated, and supported on the AP (n = 12) for 684 ± 228 min (range 195–3077 min). UV flow was subphysiologic (p = .002), while heart rate was elevated on the AP compared with in utero controls (p = .0007). We observed an inverse relationship between heart rate and UV flow (r2 = .4527; p < .001) with progressive right ventricular enlargement that was associated with reduced contractility and ultimately hydrops and circulatory collapse. We attribute this to excessive afterload imposed by supraphysiologic circuit resistance and augmented sympathetic activity. We conclude that short‐term support of the preterm piglet on the AP is feasible, although we have not been able to attain normal fetal physiology. In the future, we propose to investigate the feasibility of an AP circuit that incorporates a centrifugal pump in our miniature pig model.

Key points Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. Abstract Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non‐communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult‐onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PnormalaO2 and SnormalaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

Key points Human placental function is evaluated using non‐invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption (VnormalO2) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VnormalO2 by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental VnormalO2 by MRI was ∼4 ml min−1 kg−1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental VnormalO2, which involves the quantification of maternal‐ and fetal‐placental blood flows, fetal oxygen delivery and VnormalO2, and the oxygen gradient between uterine‐ and umbilical‐venous blood, providing a comprehensive assessment of placental function with clinical potential. Abstract It has not been feasible to perform routine clinical measurement of human placental oxygen consumption (VnormalO2) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non‐invasively quantify in utero placental and fetal oxygen delivery (DnormalO2) and VnormalO2 in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase‐contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine‐ and umbilical‐placental vessels, allowing calculation of uteroplacental and fetal DnormalO2 and VnormalO2. Maternal DnormalO2 (ml min−1 kg−1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal DnormalO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VnormalO2 (ml min−1 kg−1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal VnormalO2 ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min−1 kg−1 fetus) decreased with advancing age (P = 0.008), while fetal VnormalO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VnormalO2 was preserved through stable umbilical flow (ml min−1 kg−1; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal VnormalO2 between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical ‘placental function test’.

The Adverse Childhood Experiences (ACEs) study (Felitti et al., 1998) has led to an understanding of how exposure to abuse, neglect, and family dysfunction in childhood are related to subsequent physical and mental health problems. These issues are important to consider during the perinatal period, with studies indicating that pregnant women who report adverse experiences in childhood may be at risk of experiencing mental health and substance use problems. This study examined the association of pregnant women’s ACEs with symptoms of depression, anxiety, posttraumatic stress, and substance use, and examined the potential buffering effect of women’s resilience against the deleterious effects of ACES on mental health and substance use. Women reported on ACES, mental health symptoms, substance use, and resilience when they were screened for participation in a perinatal psychosocial support intervention, which was integrated into obstetrical clinics in a Southern academic medical center. Almost a quarter of the 303 women in this sample reported four or more ACEs, indicating significant risk. Those reporting more overall ACEs also reported more symptoms of depression, posttraumatic stress, and increased risk of tobacco use. Unique effects of specific ACEs subtypes were also found. Women exposed to child maltreatment reported more anxiety, depression, and posttraumatic stress symptoms, and were at risk for tobacco, cannabis, or opioid use during pregnancy. Women exposed to household dysfunction reported more posttraumatic stress symptoms and were at increased risk of tobacco and alcohol use during pregnancy. Women’s resilience attenuated effects of household dysfunction on posttraumatic stress symptoms.

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Introduction: Novel imaging measurements of placental development are difficult to validate due to the invasive nature of gold-standard procedures. Animal studies have been important in validation of magnetic resonance imaging (MRI) measurements in invasive preclinical studies, as they allow for controlled experiments and analysis of multiple time-points during pregnancy. This study characterises the longitudinal diffusion and perfusion properties of sheep placentomes using MRI, measurements that are required for future validation studies. Methods: Pregnant ewes were anaesthetised for a MRI session on a 3T scanner. Placental MRI was used to classify placentomes morphologically into three types based on their shape and size at two gestational ages. To validate classification accuracy, placentome type derived from MRI data were compared with placentome categorisation results after delivery. Diffusion-Weighted MRI and T2-relaxometry were used to measure a broad range of biophysical properties of the placentomes. Results: MRI morphological classification results showed consistent gestational age changes in placentome shape, as supported by post-delivery gold standard data. The mean apparent diffusion coefficient was significantly higher at 110 days gestation than at late gestation (~140 days; term, 150 days). Mean T2 was higher at mid gestation (152.2 ± 58.1 ms) compared to late gestation (127.8 ms ± 52.0). Significantly higher perfusion fraction was measured in late gestation placentomes that also had a significantly higher fractional anisotropy when compared to the earlier gestational age. Discussion: We report baseline measurements of techniques common in placental MRI for the sheep placenta. These measurements are essential to support future validation measurements of placental MRI techniques.