Convergence of placenta biology and genetic risk for schizophrenia | Nature Medicine

Defining the environmental context in which genes enhance disease
susceptibility can provide insight into the pathogenesis of complex
disorders. We report that the intra-uterine environment modulates the
association of schizophrenia with genomic risk (in this study,
genome-wide association study–derived polygenic risk scores (PRSs)). In
independent samples from the United States, Italy, and Germany, the
liability of schizophrenia explained by PRS is more than five times
greater in the presence of early-life complications (ELCs) compared with
their absence. Patients with ELC histories have significantly higher
PRS than patients without ELC histories, which is confirmed in
additional samples from Germany and Japan. The gene set composed of
schizophrenia loci that interact with ELCs is highly expressed in
placenta, is differentially expressed in placentae from complicated in
comparison with normal pregnancies, and is differentially upregulated in
placentae from male compared with female offspring. Pathway analyses
reveal that genes driving the PRS-ELC interaction are involved in
cellular stress response; genes that do not drive such interaction
implicate orthogonal biological processes (for example, synaptic
function). We conclude that a subset of the most significant genetic
variants associated with schizophrenia converge on a developmental
trajectory sensitive to events that affect the placental response to
stress, which may offer insights into sex biases and primary prevention.

Exogenous microRNAs in maternal food pass through placenta, regulate fetal gene expression

In a new study published in the Protein & Cell, Chen-Yu

Zhang's group at Nanjing University reports that small non-coding RNAs
in maternal food can transfer through placenta to regulate fetal gene
expression.
MicroRNAs (miRNA) are a class of noncoding RNAs with lengths of
approximately 22 nucleotides that bind to target messenger RNAs to
inhibit protein translation. In previous studies, the same group has
found that plant miRNAs can enter into the host blood and tissues via
the route of food-intake. The food-derived exogenous miRNAs are
absorbed, packaged into microvesical (MV) and then secreted into
circulation by cells of animal GI tract. More importantly, once inside
the host, the food-derived exogenous miRNAs can regulate host physiology
by regulating host "target" genes in the cross-kingdom manner. In
support of this new concept, they have also found a plant microRNA,
MIR2911, which is enriched in honeysuckle, directly targets influenza A viruses (IAV) including H1N1, H5N1 and H7N9. Drinking of honeysuckle soup can prevent IAV infection and reduce H5N1-induced mice death.
Here, they report another surprising finding that exogenous plant miRNAs
and artificial synthetic small influence RNAs (siRNAs) can transfer
through the placenta and directly regulate fetus gene expression.
Firstly, exogenous plant miRNAs was detected in human umbilical cord
blood, amniotic fluid as well as animal fetuses with certain level. When
pregnant mice were administrated honeysuckle soup (the exogenous plant
microRNAs are physiological concentration in food), the plant MIR2911
was detected in fetus liver at a significant level. Finally, feeding
pregnant mice with synthetic alpha-fetoprotein (AFP, only expressed in
fetus liver) siRNA decreased significantly AFP mRNA and protein levels.
They have further demonstrated that MV- driven small RNAs are able to
pass through placenta.

Placental cells may prevent viruses from passing from mother to baby

 "Cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her growing baby and can transfer that trait to other kinds of cells, according to researchers at Magee-Womens Research Institute (MWRI) and the University of Pittsburgh School of Medicine. Their findings, published in the early online version of the Proceedings of the National Academy of Sciences, shed new light on the workings of the placenta and could point to new approaches to combat viral infections during pregnancy."

PNAS

Human placental trophoblasts confer viral resistance to recipient cells