The human gestational sac as a choriovitelline placenta during early pregnancy; the secondary yolk sac and organoid models.

The yolk sac is phylogenetically the oldest of the extra-embryonic membranes and plays important roles in nutrient transfer during early pregnancy in many species. In the human this function is considered largely vestigial, in part because the secondary yolk sac never makes contact with the inner surface of the chorionic sac. Instead, it is separated from the chorion by the fluid-filled extra-embryonic coelom and attached to the developing embryo by a relatively long vitelline duct.

Ambient air pollution and adverse birth outcomes: A review of underlying mechanisms.

Epidemiological data provide varying degrees of evidence for associations between prenatal exposure to ambient air pollutants and adverse birth outcomes (suboptimal measures of fetal growth, preterm birth and stillbirth). To assess further certainty of effects, this review examines the experimental literature base to identify mechanisms by which air pollution (particulate matter, nitrogen dioxide and ozone) could cause adverse effects on the developing fetus. It likely that this environmental insult impacts multiple biological pathways important for sustaining a healthy pregnancy, depending upon the composition of the pollutant mixture and the exposure window owing to changes in physiologic maturity of the placenta, its circulations and the fetus as pregnancy ensues.

Genomic Selection Signals in Andean Highlanders Reveal Adaptive Placental Metabolic Phenotypes That Are Disrupted in Preeclampsia.

Background: The chronic hypoxia of high-altitude residence poses challenges for tissue oxygen supply and metabolism. Exposure to high altitude during pregnancy increases the incidence of hypertensive disorders of pregnancy and fetal growth restriction and alters placental metabolism. High-altitude ancestry protects against altitude-associated fetal growth restriction, indicating hypoxia tolerance that is genetic in nature.

Protocol for culturing the endocrine junctional zone of the mouse placenta in serum-free medium.

The lack of a suitable explant culture system restricts the study of factors secreted by the mouse placenta into maternal circulation. Here, we present a protocol for culturing the endocrine junctional zone of the mouse placenta, free from the decidua and labyrinthine layers in serum-free medium. We describe steps for dissecting and separating layers, dicing tissue, and culture setup.

The human placenta: new perspectives on its formation and function during early pregnancy.

The placenta has evolved to support the development of the embryo and fetus during the different intrauterine periods of life. By necessity, its development must precede that of the embryo. There is now evidence that during embryogenesis and organogenesis, the development of the human placenta is supported by histotrophic nutrition secreted from endometrial glands rather than maternal blood.

Oxidized β-Carotene Is a Novel Phytochemical Immune Modulator That Supports Animal Health and Performance for Antibiotic-Free Production.

Oxidized β-carotene (OxBC), a phytochemical that occurs naturally in plants, is formed by the spontaneous reaction of β-carotene with ambient oxygen. Synthetic OxBC, obtained by full oxidation of β-carotene with air, shows considerable promise as an in-feed antimicrobial alternative additive that enhances health and performance in livestock. OxBC is predominantly composed of β-carotene-oxygen copolymers that have beneficial immune-modulating effects that occur within the innate immune system by priming it to face microbial challenges and by mitigating the inflammatory response.

Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism.

Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity.

Placental F-Neuroprostanes and F-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity.

We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F-Neuroprostanes and F-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (n=11), obesity (n=7) and overweight/obesity+GDM (n=7) groups. F-Neuroprostanes and F-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM.

Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach.

Effect of Oxidized β-Carotene on Swine Growth Performance under Commercial Production Conditions in Vietnam.

The effects of oxidized β-carotene (OxBC) were determined upon the growth performance of swine through their full growth cycle under commercial production conditions in Vietnam. Five hundred 28-day-old-weaned barrows and gilts were used in a 140-day complete wean-to-finish feeding trial. Animals were randomized by weight, and each pen contained 20 pigs with the same ratio of barrows to gilts.

Elevated homocysteine activates unfolded protein responses and causes aberrant trophoblast differentiation and mouse blastocyst development.

Hyperhomocysteinemia may arise from folate/vitamin B deficiency, genetic polymorphisms, kidney disease, or hypothyroidism. It is associated with an increased risk of early pregnancy loss and placenta-related complications of pregnancy, including pre-eclampsia and fetal growth restriction. While the majority of studies of hyperhomocysteinemia focus on epigenetic changes secondary to metabolic disruption, the effects of homocysteine toxicity on placental development remain unexplored.

Safety and uptake of fully oxidized β-carotene.

Spontaneous oxidation of β-carotene yields a polymer-rich product (OxBC) together with minor amounts of many apocarotenoids. OxBC's activity extends β-carotene's benefits beyond vitamin A, finding utility in supporting health in livestock, pets, and humans. Although the naturally occurring form of OxBC is consumed in foods and feeds, a direct demonstration of synthetic OxBC's safety provides additional support for its usage.

Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring.

Background: Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology.

New insights into the etiopathology of placenta accreta spectrum.

Placenta accreta has been described as a spectrum of abnormal attachment of villous tissue to the uterine wall, ranging from superficial attachment to the inner myometrium without interposing decidua to transmural invasion through the entire uterine wall and beyond. These descriptions have prevailed for more than 50 years and form the basis for the diagnosis and grading of accreta placentation. Accreta placentation is essentially the consequence of uterine remodeling after surgery, primarily after cesarean delivery.

The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth.

In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here, we demonstrate, through fetal, endothelial, hematopoietic, and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The angiocrine effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signaling.

Joan Hunt Senior award lecture: New tools to shed light on the 'black box' of pregnancy.

Correct establishment of the placenta is critical to the success of a pregnancy, but many of the key events take place during or shortly after implantation and are inaccessible for study. This inaccessibility, coupled with the lack of a suitable preclinical animal model, means that knowledge of human early placental development and function is extremely limited. Hence, the first trimester is often referred to as the 'black box' of pregnancy.

Placentation in the Human and Higher Primates.

Placentation in humans is precocious and highly invasive compared to other mammals. Implantation is interstitial, with the conceptus becoming completely embedded within the endometrium towards the end of the second week post-fertilization. Villi initially form over the entire surface of the chorionic sac, stimulated by histotrophic secretions from the endometrial glands.

Failure of placental detachment in accreta placentation is associated with excessive fibrinoid deposition at the utero-placental interface.

Background: The main histopathologic diagnostic criteria for the diagnosis of placenta accreta for more than 80 years has been the finding of a direct attachment of the villous tissue to the superficial myometrium or adjacent to myometrial fibers without interposing decidua. There have been very few detailed histopathologic studies in pregnancies complicated by placenta accreta spectrum disorders and our understanding of the pathophysiology of the condition remains limited.

Objective: To prospectively evaluate the microscopic changes used in grading and to identify changes that might explain the abnormal placental tissue attachment.

Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity.

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women.

Excessive endoplasmic reticulum stress drives aberrant mouse trophoblast differentiation and placental development leading to pregnancy loss.

Key Points: Endoplasmic reticulum (ER) stress promotes placental dysmorphogenesis and is associated with poor pregnancy outcomes. We show that unfolded protein response signalling pathways located in the ER drive differentiation of mouse trophoblast stem cells into trophoblast subtypes involved in development of the placental labyrinth zone and trophoblast invasion. In a mouse model of chronic ER stress (Eif2s1 ), higher ER stress in homozygous blastocysts is accompanied by reduced trophectoderm cell number and developmental delay and also is associated with an increased incidence of early pregnancy loss.

BAP1/ASXL complex modulation regulates epithelial-mesenchymal transition during trophoblast differentiation and invasion.

Normal function of the placenta depends on the earliest developmental stages when trophoblast cells differentiate and invade into the endometrium to establish the definitive maternal-fetal interface. Previously, we identified the ubiquitously expressed tumour suppressor BRCA1-associated protein 1 (BAP1) as a central factor of a novel molecular node controlling early mouse placentation. However, functional insights into how BAP1 regulates trophoblast biology are still missing.

Menstrual flow as a non-invasive source of endometrial organoids.

Assessment of the endometrium often necessitates a biopsy, which currently involves an invasive, transcervical procedure. Here, we present an alternative technique based on deriving organoids from menstrual flow. We demonstrate that organoids can be derived from gland fragments recovered from menstrual flow.