Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI

Abstract

The srbi gene encodes a lipoprotein receptor with high affinity for high density lipoprotein that is mainly expressed in the liver and in steroidogenic tissues. Disruption of this gene in mice and mutations in humans lead to alterations in lipoprotein metabolism and/or fertility. During murine development, scavenger receptor class B member I (SR-BI) is present in the yolk sac and the placenta and is only expressed in the embryo itself late in gestation. In humans, it has been detected in trophoblast cells and placenta. Although the proportion of mice carrying a null mutation in SR-BI obtained from heterozygous intercrosses is lower than the expected by the Mendelian ratio, suggesting the involvement of this receptor in intrauterine development, the cause of this demise has remained unknown. In this work, we show that embryos lacking SR-BI exhibit a high prevalence of exencephaly with a sex bias toward females. Immunolocalization studies confirmed that SR-BI is not expressed in the embryo at early stages of development and allowed a more detailed description of its localization in the cells that mediate maternal-fetal transport of nutrients. SR-BI-null embryos contain less cholesterol than their wild-type littermates, suggesting the involvement of SR-BI in materno-fetal cholesterol transport. Newborn SR-BI-deficient pups exhibit intrauterine growth restriction, suggesting that this receptor is also important for fetal growth. Altogether, the results of our work suggest that the presence of SR-BI in extraembryonic tissues is involved in the maternal-fetal transport of cholesterol and/or other lipids with a role during neural tube closure and fetal growth.

Deficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice Lacking Lipoprotein Receptor SR-BI

“…TGC play a critical role in embryonic uptake of various nutrients from the maternal blood supply before the establishment of a mature placenta 6 . Despite the prominent role of SR-BI in cholesterol uptake 1 and the key role of cholesterol during embryonic development 7 , we have shown that the embryonic cholesterol content is similar in SR-BI +/+ and SR-BI −/− embryos 5 .…”

“…This evidence, together with the fact that SR-BI is present in murine trophoblasts involved in maternal-foetal nutrient exchange at different stages of gestation 4 , led researchers to postulate that this HDL receptor might be involved in embryonic development. We recently showed that nearly 50% of SR-BI −/− embryos fail to close the anterior neural tube and develop cranial NTD and exencephaly 5 , leading to perinatal death, which explains the deviation from the Mendelian ratio previously reported in weaned SR-BI null mice 3 . Among the spectrum of defective neurulation conditions conferred by abnormal closure at different portions of the neural tube, only cranial NTD is observed in SR-BI −/− embryos.…”

“…During murine early development, SR-BI is not detected in the embryo itself but rather in trophoblast giant cells (TGC) from the parietal yolk sac 4, 5 . TGC play a critical role in embryonic uptake of various nutrients from the maternal blood supply before the establishment of a mature placenta 6 .…”

Maternal–fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor‐related protein 2

“…Absence of these cholesterol transporters in mouse models show different phenotypes, ranging from early developmental arrest and exencephaly in scavenger receptor class B deficient embryos 16 , to no birth defects in low density lipoprotein receptor knockout pups 17 .…”

Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle

“…All rights reserved. closure and fetal growth (Santander et al, 2013). Previous research had demonstrated that SR-B1 was expressed in theca internal cells (T-I) at all stages of follicular development and in corpus luteum cells (CL) of rat ovaries (Johnson et al, 1998;Mizutani et al, 1997).…”