Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: In mice bearing an SR-BI promoter mutation that resulted in decreased expression of the receptor, hepatic expression of the receptor was reduced by 53% with a corresponding increase in total plasma cholesterol levels of 50-70% in SR-BI att mice, attributable almost exclusively to elevated plasma HDL. In addition to increased HDL-CE, HDL phospholipids and apo A-1 levels were elevated, and there was an increase in HDL particle size in mutant mice Varban et al. (1998).

Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - non-ovarian defect
Comment: Trigatti B,et al 1999 reported the influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. The authors used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility. Although the mechanisms underlying the effects of SR-BI loss on reproduction and atherosclerosis have not been established, potential causes include changes in (i) plasma lipoprotein levels and/or structure, (ii) cholesterol flux into or out of peripheral tissues (ovary, aortic wall), and (iii) reverse cholesterol transport, as indicated by the significant reduction of gallbladder bile cholesterol levels in SR-BI and SR-BI/apolipoprotein E double knockout mice relative to controls.

Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - non-ovarian defect
Comment: Miettinen HE, et al 2001 reported abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice. . Mammalian female fertility depends on complex interactions between the ovary and the extraovarian environment (e.g., the hypothalamic-hypophyseal ovarian axis). The role of plasma lipoproteins in fertility was examined using HDL-receptor SR-BI knockout (KO) mice. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes, and are infertile. Fertility was restored when the structure and/or quantity of abnormal HDL was altered by inactivating the apoAI gene or administering the cholesterol-lowering drug probucol. This suggests that abnormal lipoprotein metabolism can cause murine infertility - implying a functional hepatic-ovarian axis - and may contribute to some forms of human female infertility.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Clinical impact of scavenger receptor class B type I gene polymorphisms on human female fertility. Yates M et al. BACKGROUND The goal of this study was to evaluate the association of SCARB1 single nucleotide polymorphisms (SNPs) and fertility outcomes in women undergoing IVF. METHODS Between November 2007 and March 2010, granulosa cells and follicular fluid were collected from women undergoing IVF. Five SCARB1 SNPs were sequenced and progesterone levels were measured in the follicular fluid. Fertility measurements were defined as the presence of gestational sac(s) and fetal heartbeat(s). RESULTS The study group consisted of 274 women (mean age of 36.4 ? 4.6 years). The racial/ethnic composition was 55% Caucasian (n = 152), 25% African-American (n = 68), 12% Asian (n = 34), 5% Hispanic, (n = 14) and 2% other (n = 6). There was a significant difference in the genotype frequencies of the SCARB1 SNPs across the groups. Subjects who were homozygous for the minor allele in the rs5888 SNP had higher follicular progesterone levels than those who were homozygous for the major allele (P = 0.03). In the Caucasian group, carriers of the minor A allele of the rs4238001 SNP had lower follicular progesterone levels compared with homozygous carriers of the major G allele (P = 0.04). In this group, follicular progesterone levels were highly predictive of the rs4238001 SNP (P = 0.03). In the entire cohort, minor allele carriers of rs4238001 did not have any viable fetuses at Day 42 following embryo transfers (P = 0.04). In the African-American group in particular, there was also an association between rs10846744 and gestational sac(s) (P = 0.006), and fetal heartbeat(s) (P = 0.005). CONCLUSIONS In part, SCARB1 rs4238001 and rs10846744 SNPs may contribute to human female infertility.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Scavenger receptor class B type 1 gene polymorphisms and female fertility. Christianson MS et al. PURPOSE OF REVIEW: Multiple studies have demonstrated a role for scavenger receptor class B type 1 (SR-B1) in female fertility. Recent studies have implicated specific SR-B1 gene polymorphisms in decreased progesterone production and suboptimal fertility outcomes. RECENT FINDINGS: The lipoprotein receptor SR-B1 has been known to mediate selective uptake of lipids into steroidogenic tissues such as the ovaries. SR-B1 plays a major role in the ability of the corpus luteum to produce progesterone, which is known to play a key role in sustaining early pregnancy. Animal studies have demonstrated that deficiency in SR-B1 results in subfertility that can be restored with addition of SR-B1 function. Single-nucleotide polymorphisms in SCARB1, the gene encoding SR-B1, have been associated with human lipid levels. Women undergoing infertility treatment with low SR-B1 expression in granulosa cells were noted to have plasma estradiol levels half the normal levels and a significantly lower number of retrieved oocytes. In vitro, deficiency of SR-B1 is associated with lower progesterone secretion in human granulosa cells. Certain SR-B1 polymorphisms have been associated with lower follicular progesterone levels and a significantly lower clinical pregnancy rate. SUMMARY: Deficiency of SR-B1, particularly due to single-nucleotide polymorphisms, could explain some features of female human infertility.

Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Ovarian Cholesterol Efflux: ABC Transporters and Follicular Fluid HDL Regulate Cholesterol Content in Mouse Oocytes. Quiroz A et al. (2019) High density lipoproteins (HDL) take up cholesterol from peripheral tissues via ABC transporters and deliver it to the liver via scavenger receptor class B type I (SR-B1), for its biliary excretion. Evidence from different mammals suggests that HDL metabolism may influence female reproduction. Indeed, HDL are the main lipoproteins in follicular fluid (FF) and their composition associates to preimplantation embryo quality. The origin of FF HDL is controversial: FF HDL are thought to derive from plasma via diffusion through the basal lamina of the follicle but their molecular structure is different from plasma HDL. SR-B1 knock-out (KO) mice have provided important evidence linking HDL metabolism and female fertility. These mice have large, cholesterol-rich circulating HDL. Females are infertile, and their fertility is restored by probucol treatment, which lowers plasma cholesterol. We recently showed that ovulated oocytes from SR-B1 KO mice have excess cholesterol and are dysfunctional. However, the mechanisms explaining how high plasma HDL cholesterol relates to cholesterol excess in oocytes, and if FF HDL regulates oocyte cholesterol homeostasis are unknown. In this work, we showed that cholesterol excess in oocytes from SR-B1 KO females precedes ovulation, and coincides with the formation of the antrum. In SR-B1 KO ovaries, immature oocytes in antral follicles, but not from preantral follicles have high cholesterol levels, determined by quantitation of filipin fluorescence. By performing cross-transplant experiments between WT mice and apolipoprotein A-I deficient (ApoA-I KO) mice, which lack the main protein component of HDL, we provide experimental evidence supporting the plasmatic origin of FF HDL. Also, we demonstrate that normalization of circulating cholesterol levels using probucol results in lowering of cholesterol content in immature and ovulated oocytes from SR-B1 KO females. Incubation of oocytes from SR-B1 KO mice with purified WT HDL results in lowering of their cholesterol content. These results, together with existing evidence suggesting that granulosa cells and oocytes are unable to take up cholesterol from FF HDL, suggest that these lipoproteins promote efflux of excess cholesterol from oocytes. In agreement with this hypothesis, we identified ABC transporters in oocytes and observed that ABCA1 KO oocytes have excess cholesterol and lower viability than WT oocytes.////////////////// Excess cholesterol induces mouse egg activation and may cause female infertility. Yesilaltay A et al. (2014) The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found that they underwent normal germinal vesicle breakdown; however, SR-BI KO eggs, which had accumulated excess cholesterol in vivo, spontaneously activated, and they escaped metaphase II (MII) arrest and progressed to pronuclear, MIII, and anaphase/telophase III stages. Eggs from fertile WT mice were activated when loaded in vitro with excess cholesterol by a cholesterol/methyl-β-cyclodextrin complex, phenocopying SR-BI KO oocytes. In vitro cholesterol loading of eggs induced reduction in maturation promoting factor and MAPK activities, elevation of intracellular calcium, extrusion of a second polar body, and progression to meiotic stages beyond MII. These results suggest that the infertility of SR-BI KO females is caused, at least in part, by excess cholesterol in eggs inducing premature activation and that cholesterol can activate WT mouse eggs to escape from MII arrest. Analysis of SR-BI KO female infertility raises the possibility that abnormalities in cholesterol metabolism might underlie some cases of human female infertility of unknown etiology.//////////////////