Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis

TY - JOUR

T1 - Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis

AU - Xie, Yiran

AU - Zhao, Fangqi

AU - Wang, Yiru

AU - Borowski, Sophia

AU - Freitag, Nancy

AU - Tirado-Gonzalez, Irene

AU - Hofsink, Naomi

AU - Matschl, Urte

AU - Plösch, Torsten

AU - Garcia, Mariana G

AU - Blois, Sandra M

N1 - © 2024. The Author(s).

PY - 2024/8/8

Y1 - 2024/8/8

N2 - Adverse intrauterine conditions may cause fetal growth restriction (FGR), a pregnancy complication frequently linked to perinatal morbidity and mortality. Although many studies have focused on FGR, the pathophysiological processes underlying this disorder are complex and incompletely understood. We have recently determined that galectin-3 (gal-3), a β-galactoside-binding protein, regulates pregnancy-associated processes, including uterine receptibility, maternal vascular adaptation and placentation. Because gal-3 is expressed at both sides of the maternal-fetal interface, we unraveled the contribution of maternal- and paternal-derived gal-3 on fetal-placental development in the prenatal window and its effects on the post-natal period. Deficiency of maternal gal-3 induced maternal gut microbiome dysbiosis, resulting in a sex-specific fetal growth restriction mainly observed in female fetuses and offspring. In addition, poor placental metabolic adaptions (characterized by decreased trophoblast glycogen content and insulin-like growth factor 2 (Igf2) gene hypomethylation) were only associated with a lack of maternal-derived gal-3. Paternal gal-3 deficiency caused compromised vascularization in the placental labyrinth without affecting fetal growth trajectory. Thus, maternal-derived gal-3 may play a key role in fetal-placental development through the gut-placenta axis.

AB - Adverse intrauterine conditions may cause fetal growth restriction (FGR), a pregnancy complication frequently linked to perinatal morbidity and mortality. Although many studies have focused on FGR, the pathophysiological processes underlying this disorder are complex and incompletely understood. We have recently determined that galectin-3 (gal-3), a β-galactoside-binding protein, regulates pregnancy-associated processes, including uterine receptibility, maternal vascular adaptation and placentation. Because gal-3 is expressed at both sides of the maternal-fetal interface, we unraveled the contribution of maternal- and paternal-derived gal-3 on fetal-placental development in the prenatal window and its effects on the post-natal period. Deficiency of maternal gal-3 induced maternal gut microbiome dysbiosis, resulting in a sex-specific fetal growth restriction mainly observed in female fetuses and offspring. In addition, poor placental metabolic adaptions (characterized by decreased trophoblast glycogen content and insulin-like growth factor 2 (Igf2) gene hypomethylation) were only associated with a lack of maternal-derived gal-3. Paternal gal-3 deficiency caused compromised vascularization in the placental labyrinth without affecting fetal growth trajectory. Thus, maternal-derived gal-3 may play a key role in fetal-placental development through the gut-placenta axis.

KW - Fetal Growth Retardation/metabolism

KW - Pregnancy

KW - Female

KW - Animals

KW - Placenta/metabolism

KW - Mice

KW - Galectin 3/metabolism

KW - Male

KW - Gastrointestinal Microbiome

KW - Mice, Inbred C57BL

KW - Humans

KW - Fetal Development

KW - Insulin-Like Growth Factor II/metabolism

KW - Trophoblasts/metabolism

U2 - 10.1038/s41419-024-06962-6

DO - 10.1038/s41419-024-06962-6

M3 - SCORING: Journal article

C2 - 39117607

VL - 15

SP - 575

JO - CELL DEATH DIS

JF - CELL DEATH DIS

SN - 2041-4889

IS - 8

ER -