Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol ?7-reductase activity in chorionic villi

Linck, Leesa M.; Hayflick, SJ; Lin, Don S.; Battaile, K.P.; Ginat, Sharon; Burlingame, T. G.; Gibson, K. Michael; Honda, Maki; Honda, Akira; Salen, Gerald; Tint, G. S.; Connor, William E.; Steiner, Robert D.

doi:10.1002/(sici)1097-0223(200003)20:3<238::aid-pd792>3.0.co;2-w

Cited by 30 publications

(19 citation statements)

References 18 publications

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“…Since then several cases referring the quantification of 7-dehydrocholesterol in amniotic fluid as well as in chorionic villus either by gas chromatography or gas chromatographymass spectrometry have been published [Irons & Tint, 1998;Chevy et al, 2005;Cardoso et al, 2005a]. The diagnosis can also be made based on the detection of low enzymatic 7-dehydrocholesterol reductase activity on cultivated amniocytes or chorionic villus [Linck et al, 2000;Ginat et al, 2004].…”

Section: Biochemical Approachsupporting

confidence: 90%

Current Issues Regarding Prenatal Diagnosis of Inborn Errors of Cholesterol Biosynthesis

Cardoso¹,

Barbosa²,

Fortuna³

et al. 2012

Prenatal Diagnosis - Morphology Scan and Invasive Methods

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Section: Biochemical Approachsupporting

confidence: 90%

Current Issues Regarding Prenatal Diagnosis of Inborn Errors of Cholesterol Biosynthesis

Cardoso¹,

Barbosa²,

Fortuna³

et al. 2012

Prenatal Diagnosis - Morphology Scan and Invasive Methods

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“…A shortage of cholesterol early in life probably disrupts the SHH-GLI signal transduction pathway [16]. Interestingly, in children with a null-mutation of the DHCR7 gene, and thus lacking endogenous cholesterol synthesis, some cholesterol is still detectable in cells and plasma after birth [17]. These data suggest that there must be an exogenous source providing some of the cholesterol needed for fetal development and growth in these fetuses.…”

Section: Cholesterol and Developmentmentioning

confidence: 99%

The Role of Maternal-Fetal Cholesterol Transport in Early Fetal Life: Current Insights1

Baardman

Kerstjens-Frederikse

Berger

et al. 2013

Biology of Reproduction

120

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The importance of maternal cholesterol as an exogenous cholesterol source for the growing embryo was first reported in studies of Smith-Lemli-Opitz syndrome. Although most of the fetus's cholesterol is synthesized by the fetus itself, there is now growing evidence that during the first weeks of life, when most organs develop, the fetus largely depends on maternal cholesterol as its cholesterol source. The maternal-fetal cholesterol transport mechanism, by transporters in both the yolk sac and placenta, is becoming better understood. This minireview summarizes current insights on maternal-fetal cholesterol transport based on in vitro and in vivo studies. As the prevalence of maternal diseases, such as diabetes, obesity, and the metabolic syndrome that adversely affect maternal cholesterol levels, is now rapidly reaching epidemic proportions, we urgently need to determine the impact of these maternal conditions on the developing human fetus.

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“…SLOS fetuses and newborns, even infants with the null/null genotype, contain cholesterol (21,22). Importantly, the severity of the SLOS phenotype is affected by the apoE isoform expressed in the mothers but not the fathers (23).…”

mentioning

confidence: 99%

Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the Golden Syrian hamster

Burke

Colvin

Myatt

et al. 2009

Journal of Lipid Research

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The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by the placenta, and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possi- Cholesterol is essential for normal fetal development. Possibly the most noted role of cholesterol is as a structural component of membranes. Sterols are also the precursor for bile acids, steroid hormones, and oxysterols, which are all synthesized by the fetus and regulate various cellular processes. Cholesterol is also required for activation of sonic hedgehog (Shh), a protein involved in brain development, and for propagation of the Shh signal (1, 2). Cholesterol is obtained endogenously by de novo synthesis and exogenously by transfer of maternal cholesterol to the fetus. Interestingly, maternal plasma triglyceride and cholesterol concentrations increase during pregnancy in humans (3, 4), possibly an adaptation to maternal and fetal needs. However, whether these changes in maternal lipoprotein concentrations result in increased transport of maternal cholesterol to the fetus is unclear.Since the fetus does not come in direct contact with the maternal circulation, maternal cholesterol destined for the fetus must initially be taken up by the placenta and yolk sac prior to transport and delivery to the fetus. Indeed, the placenta and yolk sac take up maternal LDL-and HDLcholesterol at relatively elevated rates compared with other peripheral tissues (5). LDL is taken up by the LDL receptor (LDLR), which is expressed abundantly in the placenta but expressed at low levels, if at all, in the yolk sac (5, 6). LDL-derived sterol is transported to the lysosome/endosome pathway where the ester bond is hydrolyzed (7). The unesterified cholesterol is then transported by NiemannThese studies were supported by grants HD34089 (LAW) and GM31651 (FS) from the...

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Fetal demise with Smith-Lemli-Opitz syndrome confirmed by tissue sterol analysis and the absence of measurable 7-dehydrocholesterol ?7-reductase activity in chorionic villi

Cited by 30 publications

References 18 publications

Current Issues Regarding Prenatal Diagnosis of Inborn Errors of Cholesterol Biosynthesis

Current Issues Regarding Prenatal Diagnosis of Inborn Errors of Cholesterol Biosynthesis

The Role of Maternal-Fetal Cholesterol Transport in Early Fetal Life: Current Insights1

Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the Golden Syrian hamster

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