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Fenvalerate (Fen) is an endocrine disruptor, capable of interfering with the activity of estrogen and androgen. Our objective was to explore the molecular mechanisms of Fen on sperm in vivo. Adult male Sprague–Dawley rats were orally exposed to 0, 0.00625, 0.125, 2.5, 30 mg/kg/day Fen for 8 weeks. Sperm morphology, differential proteomics of sperm and testes, bioinformatic analysis, western blotting (WB), and RT‐PCR were used to explore the mechanism of Fen on sperm. Data showed that low Fen doses significantly induced sperm malformations. In sperm proteomics, 47 differentially expressed (DE) proteins were enriched in biological processes (BPs) related to energy metabolism, response to estrogen, spermatogenesis; and enriched in cellular components (CCs) relating to energy‐metabolism, sperm fibrous sheath and their outer dense fibers. In testicular proteomics, 56 DE proteins were highly associated with mRNA splicing, energy metabolism; and enriched in CCs relating to vesicles, myelin sheath, microtubules, mitochondria. WB showed that the expression of selected proteins was identical to their tendency in 2D gels. Literature indicates that key DE proteins in proteomic profiles (such as Trap1, Hnrnpa2b1, Hnrnpk, Hspa8, and Gapdh) are involved in P53‐related processes or morphogenesis or spermatogenesis. Also, P53 mRNA and protein levels were significantly increased by Fen; bioinformatic re‐analysis showed that 88.5% DE proteins and P53 formed a complex interacting network, and the key DE proteins were coenriched with P53‐related BPs. Results indicate that key DE proteins of proteome underlying sperm malformations of rats exposed to low Fen doses are highly related to P53. [ABSTRACT FROM AUTHOR]

Whole‐rock major‐trace elemental, whole‐rock Sr–Nd, and zircon U–Pb–Hf isotopic analyses have been carried out on two suites of Early Cretaceous granitic dykes in the western Dabie Orogen (Central China) with the aim of addressing their petrogenesis and geodynamic significance. LA‐ICPMS zircon U–Pb dating reveals that the E‐W‐trending granitic dykes have emplacement ages of 133.9 ± 1.6 and 132.8 ± 1.0 Ma, while the NW‐trending granitic dykes have emplacement ages of 121.4 ± 0.9 and 120.5 ± 0.7 Ma. These rocks have high concentrations of SiO2 and K2O, belonging to the high‐K calc‐alkaline and shoshonitic series. They are metaluminous to peraluminous and are mainly fractionated I‐type granite. The E‐W‐trending granites have moderate initial 87Sr/86Sr ratios (0.70614 to 0.70878) and negative εNd(t) values varying from −16.2 to −17.2 with two‐stage Nd model ages of 2.20 to 2.43 Ga. They exhibit a narrow range of zircon εHf(t) values (−22.34 to −23.70) with two‐stage Hf model ages of 2.31 to 2.36 Ga. These isotopic signatures suggest a homogeneous crustal source without significant magma contamination or mixing. The NW‐trending granites have initial 87Sr/86Sr ratios ranging from 0.70774 to 0.71034 and negative εNd(t) values varying from −10.9 to −9.5 with two‐stage Nd model ages of 1.69 to 1.80 Ga. They yield variable zircon εHf(t) values of −17.06 to −0.39 with two‐stage Hf model ages of 1.07 to 1.99 Ga, implying heterogeneous crustal signatures with minor mantle materials involved. Combining the geological, geochemical, and isotopic evidences, the E‐W‐trending granitic dykes are considered to be derived from partial melting of crustal materials under normal thickness during a transitional period following the tectonic collapse, while the NW‐trending granitic dykes resulted from crust melting in an extensional setting, most likely induced by the asthenospheric upwelling. Our results support that the western Dabie Orogen could have experienced S‐N‐directed compression (pre. 133 Ma), S‐N‐directed extension (ca. 133 Ma), and general E‐W‐directed extension (ca. 120 Ma). We propose that the Dabie Orogen has experienced tectonic collapse of the thickened lower crust and also has been affected by the subduction of the Izanagi (or Palaeo‐Pacific) Plate during the Early Cretaceous. [ABSTRACT FROM AUTHOR]

Spermatogonial stem cells ( SSCs) are undifferentiated cells that are required to maintain spermatogenesis throughout the reproductive life of mammals. Although SSC transplantation and culture provide a powerful tool to identify the mechanisms regulating SSC function, the precise signalling mechanisms governing SSC self-renewal and specific surface markers for purifying SSCs remain to be clearly determined. In the present study, we established a steady SSC culture according to the method described by Shinohara's lab. Fertile progeny was produced after transplantation of cultured SSCs into infertile mouse testis, and the red fluorescence exhibited by the culture cell membranes was stably and continuously transmitted to the offspring. Next, via advanced mass spectrometry and an optimized proteomics platform, we constructed the proteome profile, with 682 proteins expressed in SSCs. Furthermore bioinformatics analysis showed that the list contained several known molecules that are regulated in SSCs. Several nucleoproteins and membrane proteins were chosen for further exploration using immunofluorescence and RT- PCR. The results showed that SALL1, EZH2, and RCOR2 are possibly involved in the self-renewal mechanism of SSCs. Furthermore, the results of tissue-specific expression analysis showed that Gpat2 and Pld6 were uniquely and highly expressed in mouse testes and cultured SSCs. The cellular localization of PLD6 was further explored and the results showed it was primarily expressed in the spermatogonial membrane of mouse testes and cultured SSCs. The proteins identified in this study form the basis for further exploring the molecular mechanism of self-renewal in SSCs and for identifying specific surface markers of SSCs. [ABSTRACT FROM AUTHOR]

Using cDNA microarray hybridization from a human testicular cDNA library, one gene exhibiting threefold difference at expression level between adult and embryo human testes was namednDnaJA1(a new alternative isoform of human DnaJA1 which was also named HDJ2/Hsdj/dj2, a human HSP40 homologue), which was believed to be involved in testis development and spermatogenesis. Multiple tissue polymerase chain reaction (PCR) results showed thatnDnaJA1expressed highly in testis and lung but low in thymus, prostate, colon and liver. The results of the other members of DnaJA1 family (GenBank accession numbers:and) showed that they were widely expressed.andwere highly expressed in sperm whilenDnaJA1was faintly expressed by reverse transcriptase PCR. Protein motif analysis ofnDnaJA1sequence revealed motifs of DnaJ.nDnaJA1was considered as type I DnaJ like the other members of DnaJA1 family. [ABSTRACT FROM AUTHOR]

Cancer metastasis remains the most poorly understood process in cancer biology. It involves the degradation of extracellular matrix (ECM) proteins by a series of 'tumour-associated' proteases. Here we report the identification of a novel protease suppressor, NYD-SP8, which is located on human chromosome 19q13.2. NYD-SP8 encodes a 27 kD GPI-anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). Co-immunoprecipitation experiments showed that NYD-SP8 binds to uPA/uPAR complexes and interfere with active uPA production. Overexpression of NYD-SP8 results in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. These data demonstrate an important role of NYD-SP8 in regulating ECM degradation, providing a novel mechanism that modulates urokinase signalling in the suppression of cancer progression.