Dissertation > Medicine, health > Preventive Medicine,Health > Health - basic science > Health Toxicology

Low Density Lipoprotein Receptor Affects the Fertility of Female Mice

Author GuoTao
Tutor ZhangCong
School Shandong Normal University
Course Cell Biology
Keywords Ldlr fertility dyslipidemia estrogen atresia
CLC R114
Type Master's thesis
Year 2014
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Dyslipidemia can result in cardiovascular disease and it is related to polycysticovary syndrome, the most common endocrine disorder among women of reproductiveage. Characteristics of dyslipidemia that positively contribute to increase levels ofplasma very low or low density lipoprotein (VLDL/LDL) cholesterol, alter lowdensity lipoprotein (LDL) composition, increase levels of plasma triglycerides withreduced high density lipoproteins (HDL).The low density lipoprotein receptor (LDLR) is a glycoprotein in the cell surfacethat plays a key role in the homeostatic control of blood cholesterol by mediating theremoval of cholesterol-containing lipoprotein particles from circulation. Lipoproteinparticles are in combination with the LDL receptor at neutral plasma pH. The mostimportant physiologic ligand for the receptor is LDL, which has apolipoprotein B100(apoB100) and several apolipoprotein E (apoE) particles, beta-very low densitylipoprotein (β-VLDL), or certain intermediate as well as part of high-densitylipoproteins and chylomicron remnants (CM). The transcription of the Ldlr gene isadjusted to cholesterol concentration in cell, hormones and growth factors.Low density lipoprotein receptor (LDLR) is responsible for taking lipoproteinparticles which carrying cholesterol into incide of cell. It has been shown to play animportanted role in lipoprotein metabolism. The Ldlr deficient (Ldlr-/-) micedeveloped severe disease as dyslipidemia and atherosclerosis and so on. Weinvestigated whether dyslipidemia caused by Ldlr knockout could harm femalereproduction and explored the mechanism. The results indicated though the number oflitters born to Ldlr null mice was not different from that of controls, the number ofpups per litter was significantly lower for Ldlr null mice. Interestingly, while Ldlr-/-mice had obesity, their ovaries weight is light. The low density lipoprotein cholesterol (LDL-C) level in serum was significantly higher in Ldlr-/-mice on D18, D42, D90andD450than wild type mice. It may be concern with uptake less cholesterol fromlipoprotein. The high density lipoprotein cholesterol (HDL-C) level in serum wassignificantly lower in Ldlr-/-mice than WT female mice. It may be associated withATP binding cassette transporter A1(ABCA1) level lower in Ldlr-/-mice. In contrast,cholesterol and triglyceride as well as total lipid levels in the ovaries of Ldlr-/-micewere greatly decreased; those indicated that Ldlr knockout influenced the lipidmetabolism in ovary. Both ovarian lipid deposition detected by Oil Red O dyeing andlipid droplets seen by transmission electron microscope further verified the decreasedlipid level in the Ldlr null mouse ovaries. Histochemical analysis of the ovariesdemonstrated there were similar number of follicles on D4between WT and Ldlr-/-mice, however the total follicles in Ldlr-/-ovaries were significantly fewer than thoseof WT mice on D18, D42and D90. Specifically, Ldlr-/-mice had fewer preantral andantral follicles on D18, while on D42, the number of primordial and antral follicles forLdlr-/-mice decreased. These results indicated that the deletion of Ldlr has an obviousaffect on the follicle development in ovaries. Furthermore, the endoplasmic reticulumswelled and became tubby in the ovaries of Ldlr-/-mice. In addition, Ldlr null micehad lower estrogen levels and spent significantly less time in estrus than controls.Superovulation assays indicated immature Ldlr knockout mice ovulated less ova thanwild type mice, which may caused by abnormal cholesterol metabolism limitedfollicles entering the growing phase and more follicles undergo atresia. These resultsindicate that lack of Ldlr results in dyslipidemia and poor fertility.

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