Iron transfer across a functional syncytialized trophoblast monolayer.

Studying iron transfer across trophoblast monolayers is crucial given the significance of iron in maintaining a healthy pregnancy and supporting fetal growth and development. To get insights into the complex mechanism of transplacental iron transfer, we developed a standardized Transwell®-based monolayer model using BeWo (clone b30) cells. Our proposed method is divided into two parts: 1.

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs). The placental "methylome" is conserved across mammals, a shared feature of many cancers, and extensively studied for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional studies to better understand this epigenetic feature; however, whether the hTSC epigenome recapitulates primary trophoblast remains unclear.

Transcriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes.

Background: During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.

Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.

The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points.

Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs).

Human placental cells are resistant to SARS-CoV-2 infection and replication.

Background: Infection during pregnancy with SARS-CoV-2 can have a serious impact on both maternal and foetal health. Clinical studies have shown that SARS-CoV-2 transmission from the mother to the foetus typically does not occur. However, there is evidence that SARS-CoV-2 can infect the placenta .

Origin, fate and function of extraembryonic tissues during mammalian development.

Extraembryonic tissues have pivotal roles in morphogenesis and patterning of the early mammalian embryo. Developmental programmes mediated through signalling pathways and gene regulatory networks determine the sequence in which fate determination and lineage commitment of extraembryonic tissues take place, and epigenetic processes allow the memory of cell identity and state to be sustained throughout and beyond embryo development, even extending across generations. In this Review, we discuss the molecular and cellular mechanisms necessary for the different extraembryonic tissues to develop and function, from their initial specification up until the end of gastrulation, when the body plan of the embryo and the anatomical organization of its supporting extraembryonic structures are established.

Emerging models of human and non-human primate placental development - Centre for Trophoblast Research 17th annual meeting 2024.

The 17th annual meeting of the Centre for Trophoblast Research (CTR) took place at the University of Cambridge, UK, on 1-2 July 2024. This year's meeting provided an opportunity to reflect on the significant advancements made recently in modelling the human placenta in vitro. The meeting featured 12 invited speakers and attracted 260 participants from 25 countries.

Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling.

The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos.

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.

Mid-late gestation leptin infusion induces placental mitochondrial and endoplasmic reticulum unfolded protein responses in a mouse model of preeclampsia.

Introduction: Preeclamptic patients, both lean and obese, present with elevated leptin levels which are associated with the development of maternal endothelial dysfunction and adverse fetal outcomes, such as growth restriction, leading to low birth weight. Recent studies in pregnant mice demonstrate that mid-late gestation leptin infusion induces clinical characteristics of preeclampsia, including elevated maternal blood pressure, maternal endothelial dysfunction and fetal growth restriction. However, whether leptin triggers placental stress responses that contribute to adverse fetal outcomes as in preeclampsia is unknown.

Pregnancy in obese women and mechanisms of increased cardiovascular risk in offspring.

Pregnancy complicated by maternal obesity contributes to an increased cardiovascular risk in offspring, which is increasingly concerning as the rates of obesity and cardiovascular disease are higher than ever before and still growing. There has been much research in humans and preclinical animal models to understand the impact of maternal obesity on offspring health. This review summarizes what is known about the offspring cardiovascular phenotype, describing a mechanistic role for oxidative stress, metabolic inflexibility, and mitochondrial dysfunction in mediating these impairments.

Overexpression of Vitis GRF4-GIF1 improves regeneration efficiency in diploid Fragaria vesca Hawaii 4.

Background: Plant breeding played a very important role in transforming strawberries from being a niche crop with a small geographical footprint into an economically important crop grown across the planet. But even modern marker assisted breeding takes a considerable amount of time, over multiple plant generations, to produce a plant with desirable traits. As a quicker alternative, plants with desirable traits can be raised through tissue culture by doing precise genetic manipulations.

Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice.

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo.

MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity.

In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed untargeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35-48 days, i.e.

Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells.

During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development.

A genetically small fetus impairs placental adaptations near term.

The placenta is a gatekeeper between the mother and fetus, adapting its structure and functions to support optimal fetal growth. Studies exploring adaptations of placentae that support the development of genetically small fetuses are lacking. Here, using a mouse model of impaired fetal growth, achieved by deleting insulin-like growth factor 2 (Igf2) in the epiblast, we assessed placental nutrient transfer and umbilical artery (UA) blood flow during late gestation.

A New Look at Immunogenetics of Pregnancy: Maternal Major Histocompatibility Complex Class I Educates Uterine Natural Killer Cells.

Our incomplete knowledge of maternal-fetal interface (MFI) physiology impedes a better understanding of the pathological mechanisms leading to pregnancy complications, such as pre-eclampsia and fetal growth restriction. At the MFI, uterine natural killer (uNK) cells do not attack fetal cells but engage in crosstalk with both fetal and maternal cells to support feto-placental development. However, mother and fetus are genetically half-mismatched and certain combinations of variable immune genes-human leukocyte antigens (HLAs) and killer-cell immunoglobulin-like receptor (KIR), indeed, the most variable gene sets in the genome-associate with pregnancy outcomes, suggesting that these interactions regulate uNK cell function.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.

Background: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored.

Objective: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy.

Using Organoids to Model Sex Differences in the Human Brain.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages.

Fetal growth restriction and placental defects in obese mice are associated with impaired decidualisation: the role of increased leptin signalling modulators SOCS3 and PTPN2.

Decidualisation of the endometrium is a key event in early pregnancy, which enables embryo implantation. Importantly, the molecular processes impairing decidualisation in obese mothers are yet to be characterised. We hypothesise that impaired decidualisation in obese mice is mediated by the upregulation of leptin modulators, the suppressor of cytokine signalling 3 (SOCS3) and the protein tyrosine phosphatase non-receptor type 2 (PTPN2), together with the disruption of progesterone (P4)-signal transducer and activator of transcription (STAT3) signalling.