TY - JOUR
T1 - The trophoblast clock controls transport across placenta in mice
AU - Demarez, Cécile
AU - de Assis, Leonardo Vinicius Monteiro
AU - Krohn, Markus
AU - Ramella, Nahuel
AU - Schwaninger, Markus
AU - Oster, Henrik
AU - Astiz, Mariana
N1 - Publisher Copyright:
© 2021. Published by The Company of Biologists Ltd.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - In mammals, 24-h rhythms of physiology and behavior are organized by a body-wide network of clock genes and proteins. Despite the well-known function of the adult circadian system, the roles of maternal, fetal and placental clocks during pregnancy are poorly defined. In the mature mouse placenta, the labyrinth zone (LZ) is of fetal origin and key for selective nutrient and waste exchange. Recently, clock gene expression has been detected in LZ and other fetal tissues; however, there is no evidence of a placental function controlled by the LZ clock. Here, we demonstrate that specifically the trophoblast layer of the LZ harbors an already functional clock by late gestation, able to regulate in a circadian manner the expression and activity of the xenobiotic efflux pump, ATP-binding cassette sub-family B member 1 (ABCB1), likely gating the fetal exposure to drugs from the maternal circulation to certain times of the day. As more than 300 endogenous and exogenous compounds are substrates of ABCB1, our results might have implications in choosing the maternal treatment time when aiming either maximal/minimal drug availability to the fetus/mother.
AB - In mammals, 24-h rhythms of physiology and behavior are organized by a body-wide network of clock genes and proteins. Despite the well-known function of the adult circadian system, the roles of maternal, fetal and placental clocks during pregnancy are poorly defined. In the mature mouse placenta, the labyrinth zone (LZ) is of fetal origin and key for selective nutrient and waste exchange. Recently, clock gene expression has been detected in LZ and other fetal tissues; however, there is no evidence of a placental function controlled by the LZ clock. Here, we demonstrate that specifically the trophoblast layer of the LZ harbors an already functional clock by late gestation, able to regulate in a circadian manner the expression and activity of the xenobiotic efflux pump, ATP-binding cassette sub-family B member 1 (ABCB1), likely gating the fetal exposure to drugs from the maternal circulation to certain times of the day. As more than 300 endogenous and exogenous compounds are substrates of ABCB1, our results might have implications in choosing the maternal treatment time when aiming either maximal/minimal drug availability to the fetus/mother.
UR - http://www.scopus.com/inward/record.url?scp=85105034229&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/8c3f9b58-6049-34f7-8422-c4493ec1221a/
U2 - 10.1242/dev.197673
DO - 10.1242/dev.197673
M3 - Journal articles
C2 - 33913482
AN - SCOPUS:85105034229
SN - 0950-1991
VL - 148
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 8
M1 - dev197673
ER -