Effects Of Apolipoprotein E On Murine Fertility

With the improvement of the living standard and the changes of life style, more andmore people become to obese, diseases associated with obesity showed a rapid growthand younger tendency. In terms of reproductive system, obesity can affect ovulationand pregnancy and increase the chance of infertility as well. Meanwhile, obesepatients are more likely to have pregnancy complications, such as hypertension,pre-eclampsia, diabetes. Obesity can increase the incidence of menstrual disorders,miscarriage, stillbirth and breast cancer, endometrial cancer and sex hormonedependent tumor and so on.Apolipoprotein (apo) family is implicated in lipid metabolism. There are apo A,apo B, apo C, apo D, apo E five types. Apolipoprotein E (Apo E) is an arginine-richapolipoprotein with a relative molecular mass of34,000Dalton and was firstidentified as a lipoprotein constituent of VLDL in1973by Shore and Shore. Apo-E isrecognized as an important molecule in serving various functions, includinglipoprotein structure maintenance, lipoprotein metabolism regulation,immunoregulation as well as neuronal repair. The attention paid to the role of apo Ein lipoprotein metabolism came from the observation of apo-E-enriched VLDLaccumulated in the plasma of patients with type III hyperlipoproteinemia, a geneticdisorder. Furthermore, apo-E is a major protein constituent of several cholesterolenriched lipoproteins, it is now known that these cholesterol enriched, apo-Econtaining lipoproteins are chylomicron (CM), VLDL remnants, and a subclass ofhigh density lipoprotein (HDL). As mentioned previously, apo-E has extensive rolesin mediating lipid metabolism. It is required for efficient receptor-mediated plasmaclearance by the liver of chylomicron remnants and very low-density lipoprotein(VLDL) remnant particles Apo-E also has a high affinity to the low densitylipoprotein receptor (LDLR). In addition, as a component of HDL subclass, apo-Eparticipates the ‘reverse cholesterol transport’(RCT) process to remove excesscholesterol from cells to the liver for biliary secretion. The apo-E deficient (Apo-E-/-) mice developed atherosclerotic plaquesspontaneously and followed with obesity apparently. We investigated whether thefatty caused by gene apo-E knockout do harm to female reproduction. The resultsdemonstrated that Apo-E-/-mice were severely hypercholesterolemic, their cholesterolmetabolism disordered, lipid accumulated in the ovary and caused the ovariesoverweighted compared to the wild-type counterparts, however, several physiologicalindices related to reproduction such as serum hormone levels, the number of ovulation,the start time of puberty and fertility ability showed no significant difference, that is tosay, the obesity induced by apo-E knockout is trivial to reproduction. But it is worthnoting that the deletion of apo-E influenced follicles development and increased theovarian follicle number and the ration of ovarian follicle atresia and apoptosis. Thenumbers of different stage follicles in different ages have obvious changes. TUNELassay confirmed the direction of the missing follicles. To a certain extent, we believethis work will augment our understanding of the role of apo-E in reproduction.