Novel genes and regulatory systems in epididymal differentiation and sperm maturation of the mouse.

Mammalian spermatozoa gain their fertilizing ability during maturation in the epididymis. Proteins and lipids secreted into the epididymal lumen remodel the sperm membrane, thereby providing the structure necessary for progressive motility and oocyte interaction. In the current study, genetically modified mouse models were utilized to determine the role of novel genes and regulatory systems in the postnatal development and function of the epididymis. Ablation of the mouse β-defensin, Defb41, altered the flagellar movements of sperm and reduced the ability of sperm to bind to the oocyte in vitro. The Defb41-deficient iCre knock-in mouse model was furthermore utilized to generate Dicer1 conditional knock-out (cKO) mice. DICER1 is required for production of mature microRNAs in the regulation of gene expression by RNA interference. Dicer1 cKO gave rise to dedifferentiation of the epididymal epithelium and an altered expression of genes involved in lipid synthesis. As a consequence, the cholesterol:polyunsaturated fatty acid ratio of the Dicer1 cKO sperm membrane was increased, which resulted in membrane instability and infertility. In conclusion, the results of the Defb41 study further support the important role of β-defensin family members in sperm maturation. The regulatory role of Dicer1 was also shown to be required for epididymal development. In addition, the study is the first to show a clear connection between lipid homeostasis in the epididymis and sperm membrane integrity. Taken together, the results give important new evidence on the regulatory system guiding epididymal development and functionSiirretty Doriast

Members of the murine Pate family are predominantly expressed in the epididymis in a segment-specific fashion and regulated by androgens and other testicular factors

<p>Abstract</p> <p>Background</p> <p>Spermatozoa leaving the testis are not able to fertilize the egg <it>in vivo</it>. They must undergo further maturation in the epididymis. Proteins secreted to the epididymal lumen by the epithelial cells interact with the spermatozoa and enable these maturational changes, and are responsible for proper storage conditions before ejaculation. The present study was carried out in order to characterize the expression of a novel <it>Pate </it>(prostate and testis expression) gene family, coding for secreted cysteine-rich proteins, in the epididymis.</p> <p>Methods</p> <p>Murine genome databases were searched and sequence comparisons were performed to identify members of the <it>Pate </it>gene family, and their expression profiles in several mouse tissues were characterized by RT-PCR. Alternate transcripts were identified by RT-PCR, sequencing and Northern hybridization. Also, to study the regulation of expression of <it>Pate </it>family genes by the testis, quantitative (q) RT-PCR analyses were performed to compare gene expression levels in the epididymides of intact mice, gonadectomized mice, and gonadectomized mice under testosterone replacement treatment.</p> <p>Results</p> <p>A revised family tree of <it>Pate </it>genes is presented, including a previously uncharacterized <it>Pate </it>gene named <it>Pate-X</it>, and the data revealed that <it>Acrv1 </it>and <it>Sslp1 </it>should also be considered as members of the <it>Pate </it>family. Alternate splicing was observed for <it>Pate-X, Pate-C </it>and <it>Pate-M</it>. All the <it>Pate </it>genes studied are predominantly expressed in the epididymis, whereas expression in the testis and prostate is notably lower. Loss of androgens and/or testicular luminal factors was observed to affect the epididymal expression of several <it>Pate </it>genes.</p> <p>Conclusions</p> <p>We have characterized a gene cluster consisting of at least 14 expressed <it>Pate </it>gene members, including <it>Acrv1, Sslp1 </it>and a previously uncharacterized gene which we named <it>Pate-X</it>. The genes code for putatively secreted, cysteine-rich proteins with a TFP/Ly-6/uPAR domain. Members of the <it>Pate </it>gene cluster characterized are predominantly expressed in the murine epididymis, not in the testis or prostate, and are regulated by testicular factors. Similar proteins are present in venoms of several reptiles, and they are thought to mediate their effects by regulating certain ion channels, and are thus expected to have a clinical relevance in sperm maturation and epididymal infections.</p

The role of Dicer1 in the male reproductive tract

Dicer1 is an RNase III enzyme necessary for microRNA (miRNA) biogenesis, as it cleaves pre-miRNAs into mature miRNAs. miRNAs are important regulators of gene expression. In recent years, several miRNA-independent roles of Dicer1 have been identified. They include the production of endogenous small interfering RNAs, detoxifying retrotransposon-derived transcripts, and binding to new targets; messenger RNAs and long noncoding RNAs. Further, in this review, the functional significance of Dicer1 in the male reproductive tract is discussed. Conditional Dicer1 knock-out mouse models have demonstrated a requisite role for Dicer in male fertility. Deletion of Dicer1 from somatic or germ cells in the testis cause spermatogenic problems rendering male mice infertile. The lack of Dicer1 in the proximal epididymis causes dedifferentiation of the epithelium, with unbalanced sex steroid receptor expression, defects in epithelial lipid homeostasis, and subsequent male infertility. In addition, Dicer1 ablation from the prostate leads to increased apoptosis of the differentiated luminal cells, followed by epithelial hypotrophy of the ventral prostate. However, further studies are needed to clarify which functions of Dicer1 are responsible for the observed phenotypes in the male reproductive tract

Kundlojalitet : En jämförande studie mellan ett offline- och onlineföretag i deras arbete med att skapa lojala kunder

Utifrån relationsmarknadsföringsperspektivet har vårdandet av relationen till kunder uppmärksammats inom marknaden för detaljhandel. Inom detta område är lojalitetsskapandet en viktig del och forskning visar tydligt på att företag som är verksamma offline respektive online arbetar med detta. Studiens syfte är att med hjälp av jämförelse och analys beskriva offline- och onlineföretags arbete med lojalitetsskapande och därmed bidra till ökad kunskap inom området. Detta leder till undersökningens frågeställning, vad finns det för skillnader mellan hur svenska online- och offlineföretag inom detaljhandeln arbetar för att få lojala kunder? För att ta reda på det har vi genomfört sju intervjuer med totalt sex anställda på två olika företag som dagligen arbetar med relationsmarknadsföring. Studien är även baserad på observationer av studieobjektens webbsidor, Facebook-, Instagram- och Youtubesidor samt företagens postala utskick. Detta för att kunna jämföra vad företagen säger att de gör med vad de faktiskt gör inom området relationsmarknadsföring, samt jämföra hur de olika företagen arbetar. De främsta teorier som denna studie baseras på handlar om hur kundklubbar hjälper företag att skapa lojala kunder. Utifrån dessa kundklubbar kan företag samla data om sina kunder för att kunna mäta denna lojalitet. Resultatet av intervjuerna och observationerna presenteras fristående från varandra. Vad gäller analysen är den indelad efter teorikapitlets presentation av teorier och modeller. Utifrån analysen har vi kunnat dra slutsatser som visar att det finns skillnader mellan företagen som beror på att de är verksamma offline respektive online. Det finns även vissa skillnader mellan företagen som inte beror på att företagen har olika syn på vad som gör kunderna lojala och vad de anser att lojalitet är. The care of the relationship between a company and a customer has gotten attention from a relationship marketing point of view in the retail market. Customer loyalty is very important and a big part of reaching success for companies and research has shown that both offline and online companies work with this. The purpose of this study is that with a comparative study between an offline and an online company contribute to the knowledge about creating loyal customers. That leads us to the question of this paper, what are the differences between Swedish offline and online companies in the retail industry regarding loyalty creating? To answer this question this paper contains seven interviews with six employees at two different companies that on a daily basis work with relationship marketing. The study is also based on observations of the company’s communities, websites and paper mailings that are sent to the customers. This has been made to make it possible to compare what the companies say that they do to what they actually do. The theories that this paper is based on, is primarily regarding customer clubs and how these help companies building loyal customers. This Customer clubs is also a method for companies to gather information about the customers so that they can measure the customer loyalty. The result of the interviews and the observations is presented separately and the analysis is based on the theory chapter’s structure. In the analysis we have made some conclusions that shows the differences between offline and online companies and their work with customer loyalty. Some of the differences is based on that the companies doesn’t have the same view on what customer loyalty is and some differences is based on the fact that they act offline versus online.