Expression of Serpinb6 serpins in germ and somatic cells of mouse gonads

Charron, Yves; Madani, Rime; Nef, Serge; Combepine, Chantal; Govin, Jérôme; Khochbin, Saadi; Vassalli, Jean‐Dominique

doi:10.1002/mrd.20385

Cited by 19 publications

(9 citation statements)

References 42 publications

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“…This phenomenon is clearly reflected by the gene networks of Jun and Cebpb in particular: most of their target genes which show increased or even specific signals in AMH-Cre Sox9 flox/flox testes (such as C3ar1 , Cd44 , Cd14 , Cebpa , Cxcl13 , H2-Aa , Icam1 , Ildr2 , Ly6d , Maob , Nupr1 , and Prdx1 ) are involved in immunological or inflammatory processes (see Mouse Genome Database for references). Interestingly, we also observed loci that play roles in down-regulating the immune response which likely reflects a stress response mechanism activated in increasingly damaged testicular tissue: for example, we found two serine protease inhibitors Serpinb6b (Serine (or cysteine) peptidase inhibitor, clade B, member 6B) and Serpina3n , [61], which are known to act on Granzymes A and B proteases secreted by cytotoxic T-lymphocytes [62,63]. Cultured human Sertoli cells - which are perhaps in a similar state of stress as Sox9 -negative Sertoli cells in degenerating testicular tissue - secrete Serpina3n which was found to bind and inhibit Granzyme B, revealing a direct mechanism of Sertoli cell-dependent immunoprotection [64].…”

Section: Discussionmentioning

confidence: 98%

Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

Lardenois

Chalmel

Barrionuevo

et al. 2010

Reprod Biol Endocrinol

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BackgroundSox9 (Sry box containing gene 9) is a DNA-binding transcription factor involved in chondrocyte development and sex determination. The protein's absence in testicular Sertoli nurse cells has been shown to disrupt testicular function in adults but little is known at the genome-wide level about molecular events concomitant with testicular break-down.MethodsTo determine the genome-wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli cells we analysed adult testicular tissue from wild-type versus mutant mice with high-density oligonucleotide microarrays and integrated the output of this experiment with regulatory motif predictions and protein-protein network data.ResultsWe report the genome-wide mRNA signature of adult testes lacking Sox9 in Sertoli cells before and after the onset of late spermatogenic failure as compared to fertile controls. The GeneChip data integrated with evolutionarily conserved Sox9 DNA binding motifs and regulatory network data identified genes involved in feminization, stress response and inflammation.ConclusionsOur results extend previous observations that genes required for female gonadogenesis are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult stage. Importantly, we identify gene networks involved in immunological processes and stress response which is reminiscent of a phenomenon occurring in a sub-group of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a potentially useful model for adult human testicular failure.

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Section: Discussionmentioning

confidence: 98%

Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

Lardenois

Chalmel

Barrionuevo

et al. 2010

Reprod Biol Endocrinol

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“…In our present study, in situ hybridization and immunohistochemistry revealed that mRNA and protein localization of SERPINB6 was restricted only to the GCs of bovine follicles. It has been demonstrated that Spi/SERPINB6, which is the mouse ortholog of SERPINB6, and two Spi3/SERPINB6 paralogs, NK13/SERPINB6b and Spi3C/SERPINB6c, were expressed in a mouse follicular somatic cells and/or oocytes [45]. A primary target protease of SERPINB6 is cathepsin G [46], whereas its gene expression is likely to be restricted to the myeloid lineage [47] while the expression in ovarian follicular cells is unknown.…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia

Hayashi

Ushizawa

Hosoe

et al. 2011

Reprod Biol Endocrinol

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BackgroundSERPINs (serine protease inhibitors) regulate proteases involving fibrinolysis, coagulation, inflammation, cell mobility, cellular differentiation and apoptosis. This study aimed to investigate differentially expressed genes of members of the SERPIN superfamily between healthy and atretic follicles using a combination of microarray and quantitative real-time PCR (QPCR) analysis. In addition, we further determined mRNA and protein localization of identified SERPINs in estradiol (E2)-active and E2-inactive follicles by in situ hybridization and immunohistochemistry.MethodsWe performed microarray analysis of healthy (10.7 +/- 0.7 mm) and atretic (7.8 +/- 0.2 mm) follicles using a custom-made bovine oligonucleotide microarray to screen differentially expressed genes encoding SERPIN superfamily members between groups. The expression profiles of six identified SERPIN genes were further confirmed by QPCR analysis. In addition, mRNA and protein localization of four SERPINs was investigated in E2-active and E2-inactive follicles using in situ hybridization and immunohistochemistry.ResultsWe have identified 11 SERPIN genes expressed in healthy and atretic follicles by microarray analysis. QPCR analysis confirmed that mRNA expression of four SERPINs (SERPINA5, SERPINB6, SERPINE2 and SERPINF2) was greater in healthy than in atretic follicles, while two SERPINs (SERPINE1 and SERPING1) had greater expression in atretic than in healthy follicles. In situ hybridization showed that SERPINA5, SERPINB6 and SERPINF2 mRNA were localized in GCs of E2-active follicles and weakly expressed in GCs of E2-inactive follicles. SERPING1 mRNA was localized in both GCs and the theca layer (TL) of E2-inactive follicles and a weak hybridization signal was also detected in both GCs and TL of E2-active follicles. Immunohistochemistry showed that SERPINA5, SERPINB6 and SERPINF2 were detected in GCs of E2-active and E2-inactive follicles. SERPING1 protein was localized in both GCs and the TL of E2-active and E2-inactive follicles.ConclusionsOur results demonstrate a characteristic expression of SERPIN superfamily member genes in bovine healthy and atretic follicles. The cell-type-and stage-specific expression of SERPINs may be associated with bovine follicular growth and atresia.

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“…As tPA is overexpressed in cultures, the levels of these conjugates would be low relative to the total tPA and therefore would not be expected to significantly reduce the bioactivity of the tPA in vitro or in vivo. Interestingly, Serpin B6 is high in gonadal tissues, so it is perhaps not surprising that it is expressed in Chinese hamster ovary cells …”

Section: Case Studiesmentioning

confidence: 99%

Experience with host cell protein impurities in biopharmaceuticals

Vanderlaan¹,

Zhu-Shimoni²,

Lin³

et al. 2018

Biotechnology Progress

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In the 40-year history of biopharmaceuticals, there have been a few cases where the final products contained residual host cell protein (HCP) impurities at levels high enough to be of concern. This article summarizes the industry experience in these cases where HCP impurities have been presented in public forums and/or published. Regulatory guidance on HCP impurities is limited to advising that products be as pure as practical, with no specified numerical limit because the risk associated with HCP exposure often depends on the clinical setting (route of administration, dose, indication, patient population) and the particular impurity. While the overall safety and purity track record of the industry is excellent, these examples illustrate several important lessons learned about the kinds of HCPs that co-purify with products (e.g., product homologs, and HCPs that react with product), and the kinds of clinical consequences of HCP impurities (e.g., direct biological activity, immunogenicity, adjuvant). The literature on industry experience with HCP impurities is scattered, and this review draws in to one reference documented examples where the data have been presented in meetings, patents, product inserts, or press releases, in addition to peer-reviewed journal articles. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:828-837, 2018.

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Expression of Serpinb6 serpins in germ and somatic cells of mouse gonads

Cited by 19 publications

References 42 publications

Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia

Experience with host cell protein impurities in biopharmaceuticals

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