Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo.

A fundamental question in animal development is how motile cells find their correct target destinations. During mating in the nematode Caenorhabditis elegans, males inject sperm through the hermaphrodite vulva into the uterus. Amoeboid sperm crawl around fertilized eggs to the spermatheca--a convoluted tube where fertilization occurs. Here, we show that polyunsaturated fatty acids (PUFAs), the precursors of eicosanoid signalling molecules, function in oocytes to control directional sperm motility within the uterus. PUFAs are transported from the intestine, the site of fat metabolism, to the oocytes yolk, which is a lipoprotein complex. Loss of the RME-2 low-density lipoprotein (LDL) receptor, which mediates yolk endocytosis and fatty acid transport into oocytes, causes severe defects in sperm targeting. We used an RNAi screen to identify lipid regulators required for directional sperm motility. Our results support the hypothesis that PUFAs function in oocytes as precursors of signals that control sperm recruitment to the spermatheca. A common property of PUFAs in mammals and C. elegans is that these fats control local recruitment of motile cells to their target tissues.

Insulin/FOXO signaling regulates ovarian prostaglandins critical for reproduction.

Abnormalities in insulin/IGF-1 signaling are associated with infertility, but the molecular mechanisms are not well understood. Here we use liquid chromatography with electrospray ionization tandem mass spectrometry to show that the C. elegans insulin/FOXO pathway regulates the metabolism of locally acting lipid hormones called prostaglandins. C. elegans prostaglandins are synthesized without prostaglandin G/H synthase homologs, the targets of nonsteroidal anti-inflammatory drugs. Our results support the model that insulin signaling promotes the conversion of oocyte polyunsaturated fatty acids (PUFAs) into F-series prostaglandins that guide sperm to the fertilization site. Reduction in insulin signaling activates DAF-16/FOXO, which represses the transcription of germline and intestinal genes required to deliver PUFAs to oocytes in lipoprotein complexes. Nutritional and neuroendocrine cues target this mechanism to control prostaglandin metabolism and reproductive output. Prostaglandins may be conserved sperm guidance factors and widespread downstream effectors of insulin actions that influence both reproductive and nonreproductive processes.

Unusual biochemical features and follicular dendritic cell expression of human Fcalpha/mu receptor.

The Fc receptor for IgA and IgM (Fcalpha/muR) is of particular interest because it can bind antibodies of both IgM and IgA isotypes and thus may play a pivotal role in systemic and mucosal immunity. Using IgM and IgA ligands and newly generated Fcalpha/muR specific monoclonal antibodies we have defined biochemical features and cellular distribution of the human Fcalpha/muR. Both recombinant and native forms of human Fcalpha/muR are expressed on the cell surface as remarkably stable homodimeric transmembrane glycoproteins that can bind specifically polymeric IgM or IgA. The only human B cells to express Fcalpha/muR, albeit at very low levels, are found in the pre-germinal center subpopulation defined by the IgD+/CD38+ phenotype. Hence the expression pattern differs from that of the mouse wherein Fcalpha/muR is expressed by both circulating and resident B cell populations. Significantly, the predominant cell type expressing the Fcalpha/muR in humans is the follicular dendritic cell of germinal centers. The Fcalpha/muR may thus function in antigen presentation and B cell selection in the germinal center response.