Skip to content

Study identifies transporter proteins responsible for human’s placenta protective ability during pregnancy.

An important function of the human placenta is to protect the fetus from detrimental substances in maternal blood, such as glucocorticoids or toxins. Placental membrane-bound transporter proteins, known as multidrug resistance proteins, protect the fetus by returning unwanted materials to the maternal circulation. Now, researchers from the University of Toronto report that bacterial and viral infections differentially influence these transporter proteins in early and late pregnancy, suggesting potential mechanisms underlying infection-related pregnancy complications such as preterm birth and fetal brain damage.

The data findings show that bacterial and viral challenges can reduce the expression of the multidrug transporters in the human placenta.  Because intrauterine infection/inflammation is relatively common during pregnancy, and associated with significant pregnancy disorders, the consequent reduction in the expression of drug transporters may expose the embryo/fetus to potentially harmful drugs, toxins, and hormones that cross from the maternal circulation at a time when it is most vulnerable.

The researchers analyzed placental tissues from patients undergoing surgical termination of pregnancy in the first trimester (8 to 10 weeks gestation) or from term elective cesarean deliveries in the third trimester (>37 weeks’ gestation). The placental explants were exposed to either lipopolysaccharide (LPS), a component of gram-negative bacterial walls to simulate bacterial infection, or polyinosinic-polycytidyic acid [poly(I:C)] to simulate viral infection.

The researchers examined the effect of bacterial or viral antigen on two multidrug transporter proteins, P-glycoprotein (P-gp; encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP; encoded by the ABCG2 gene) from the tissues taken at the different stages of pregnancy. Exposure with LPS for 24 hours decreased P-gp- and BCRP-related mRNA and protein levels in the first-trimester explants, whereas no effects were seen in the third-trimester explants. In contrast, poly(I:C) decreased ABCB1 mRNA levels in the third trimester but not the first trimester. Poly(I:C) did not change ABCG2 mRNA or BCRP levels at either time in pregnancy.

The team also looked at the effects of pregnancy on the receptors for LPS (toll-like receptor-4, TLR-4) and poly(I:C) (TLR-3). TLR-3/4 mRNA expression increased from the first to the third trimesters, and the location changed from the inner layer to the outer layer of the placenta at term. This was the first time that a gestational age-dependent pattern of expression was found for TLR-3. The expression of the receptors was not changed by LPS at either time in pregnancy, whereas poly(I:C) decreased the expression of both receptors in the third trimester with no effect in the first trimester.

TLRs are essential components of the signaling network within the innate immune response, which can stimulate the release of cytokines, explain the researchers. They go on to add that consistently, both LPS and poly(I:C) elicited strong cytokine and chemokine responses (as measured by interleukin-8 and CCL2) in both first and third trimester explants.

The team state that until this study, the extent to which bacterial- and viral-associated infection affects placental expression of ABC transporters at different stages of gestation in humans was largely unexplored.

The data findings suggest that infection and inflammation are capable of inducing changes in the levels of drug transporters. The results also suggest that the placenta exhibits a differential response to infectious agents and this effect is greater for bacterial challenge compared to viral challenge.

Moreover, the team surmise that the first-trimester placenta appears to be more sensitive to the effects of bacterial infection, potentially leading to increased exposure of the embryo/fetus to drugs and toxins at a critical time in development, whereas viral infections may disrupt fetal protection in later stages of pregnancy.

Source:  University of Toronto

 

Changes in placenta's protective ability during pregnancy linked to transporter proteins - healthinnovations

 

 

 

Healthinnovations View All

Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.

Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.

Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

One thought on “Study identifies transporter proteins responsible for human’s placenta protective ability during pregnancy. Leave a comment

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.