Evidence of macrophage modulation in the mouse pubic symphysis remodeling during the end of first pregnancy and postpartum.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 07 2020
24 07 2020
Historique:
received:
16
04
2020
accepted:
30
06
2020
entrez:
26
7
2020
pubmed:
28
7
2020
medline:
19
12
2020
Statut:
epublish
Résumé
In mouse pregnancy, pubic symphysis (PS) remodels into an elastic interpubic ligament (IpL) in a temporally regulated process to provide safe delivery. It restores at postpartum to assure reproductive tract homeostasis. Recently, macrophage localization in the IpL and dynamic changes in the expression of inflammatory mediators observed from the end of pregnancy (D18, D19) to early days postpartum (1dpp, 3dpp) highlighted the necessity of the identification of the key molecules involved in innate immune processes in PS remodeling. Therefore, this study uses morphological and high-sensitivity molecular techniques to identify both macrophage association with extracellular matrix (ECM) remodeling and the immunological processes involved in PS changes from D18 to 3dpp. Results showed macrophage association with active gelatinases and ECM components and 25 differentially expressed genes (DEGs) related to macrophage activities in interpubic tissues from D18 to 3dpp. Additionally, microarray and proteomic analysis showed a significant association of interpubic tissue DEGs with complement system activation and differentially expressed proteins (DEPs) with phagocytosis, highlighting the involvement of macrophage-related activities in mouse PS remodeling. Therefore, the findings suggest that PS ECM remodeling is associated with evidence of macrophage modulation that ensures both IpL relaxation and fast PS recovery postpartum for first labor.
Identifiants
pubmed: 32709949
doi: 10.1038/s41598-020-68676-x
pii: 10.1038/s41598-020-68676-x
pmc: PMC7381608
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12403Références
Sherwood, O. Relaxin. In The Physiology of Reproduction. (ed Neill E. Ka. J. D.) 861–1009 (Raven Press, New York, 1994).
Mahendroo, M. Cervical remodeling in term and preterm birth: Insights from an animal model. Reproduction 143, 429–438. https://doi.org/10.1530/REP-11-0466 (2012).
doi: 10.1530/REP-11-0466
pubmed: 22344465
Akgul, Y., Holt, R., Mummert, M., Word, A. & Mahendroo, M. Dynamic changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth. Endocrinology 153, 3493–3503. https://doi.org/10.1210/en.2011-1950 (2012).
doi: 10.1210/en.2011-1950
pubmed: 22529214
pmcid: 3380303
Ruscheinsky, M., De la Motte, C. & Mahendroo, M. Hyaluronan and its binding proteins during cervical ripening and parturition: Dynamic changes in size, distribution and temporal sequence. Matrix Biol. 27, 487–497. https://doi.org/10.1016/j.matbio.2008.01.010 (2008).
doi: 10.1016/j.matbio.2008.01.010
pubmed: 18353623
pmcid: 2492578
Wieslander, C. K. et al. Regulation of elastolytic proteases in the mouse vagina during pregnancy, parturition, and puerperium. Biol. Reprod. 78, 521–528. https://doi.org/10.1095/biolreprod.107.063024 (2008).
doi: 10.1095/biolreprod.107.063024
pubmed: 18003950
Storey, E. Relaxation in the pubic symphysis of the mouse during pregnancy and after relaxin administration, with special reference to the behavior of collagen. J. Pathol. Bacteriol. 74, 147–162 (1957).
doi: 10.1002/path.1700740117
Joazeiro, P. P., Consonni, S. R., Rosa, R. G. & Toledo, O. M. S. Peri-partum changes to mouse pubic symphysis. In The Guide to Investigation of Mouse Pregnancy 1st edn (eds Croy, A., Yamada, A. T., DeMayo, F. J. & Adamson, S. L.) 403–417 (Elsevier, Amsterdam, 2014).
Rosa, R. G., Akgul, Y., Joazeiro, P. P. & Mahendroo, M. Changes of large molecular weight hyaluronan and versican in the mouse pubic symphysis through pregnancy. Biol. Reprod. 86, 44. https://doi.org/10.1095/biolreprod.111.093229 (2012).
doi: 10.1095/biolreprod.111.093229
pubmed: 22011392
Consonni, S. R. et al. Elastic fiber assembly in the adult mouse pubic symphysis during pregnancy and postpartum. Biol. Reprod. 86(151–1), 151–10. https://doi.org/10.1095/biolreprod.111.095653 (2012).
doi: 10.1095/biolreprod.111.095653
Pinheiro, M. C. et al. Histochemical and ultrastructural study of collagen fibers in mouse pubic symphysis during late pregnancy. Micron 35, 685–693. https://doi.org/10.1016/j.micron.2004.04.007 (2004).
doi: 10.1016/j.micron.2004.04.007
pubmed: 15288647
Pinheiro, M. C. et al. Ultrastructural, immunohistochemical and biochemical analysis of glycosaminoglycans and proteoglycans in the mouse pubic symphysis during pregnancy. Cell Biol. Int. 29, 458–471. https://doi.org/10.1016/j.cellbi.2004.11.025 (2005).
doi: 10.1016/j.cellbi.2004.11.025
pubmed: 15951206
Consonni, S. R. et al. Recovery of the pubic symphysis on primiparous young and multiparous senescent mice at postpartum. Histol. Histopathol. 27, 885–896 (2012).
pubmed: 22648544
Castelucci, B. G. et al. Time-dependent regulation of morphological changes and cartilage differentiation markers in the mouse pubic symphysis during pregnancy and postpartum recovery. PLoS ONE 13, e0195304. https://doi.org/10.1371/journal.pone.0195304 (2018).
doi: 10.1371/journal.pone.0195304
pubmed: 29621303
pmcid: 5886480
Hall, K. Changes in the bone and cartilage of the symphysis pubis of the mouse during pregnancy and after parturition, as revealed by metachromatic staining and the periodic acid-schiff technique. J. Endocrinol. 11, 210. https://doi.org/10.1677/joe.0.0110210 (1954).
doi: 10.1677/joe.0.0110210
pubmed: 13201710
Borazjani, A., Couri, B., Balog, B. & Damaser, M. Mp1-13 pubic symphysis length is correlated with pelvic organ prolapse in lysyl oxidase like-1 knockout mice. J. Urol. 191, e6. https://doi.org/10.1016/j.juro.2014.02.111 (2014).
doi: 10.1016/j.juro.2014.02.111
Rosa, R. G. et al. Temporal changes in matrix metalloproteinases, their inhibitors, and cathepsins in mouse pubic symphysis during pregnancy and postpartum. Reprod. Sci. 18, 963–977. https://doi.org/10.1177/1933719111401657 (2011).
doi: 10.1177/1933719111401657
pubmed: 21960510
Garcia, E. A. et al. Hyaluronan involvement in the changes of mouse interpubic tissue during late pregnancy and postpartum. Cell Biol. Int. 32, 913–919. https://doi.org/10.1016/j.cellbi.2008.04.006 (2008).
doi: 10.1016/j.cellbi.2008.04.006
pubmed: 18499485
Gomez-Lopez, N., StLouis, D., Lehr, M. A., Sanchez-Rodriguez, E. N. & Arenas-Hernandez, M. Immune cells in term and preterm labor. Cell Mol. Immunol. 11, 571–581. https://doi.org/10.1038/cmi.2014.46 (2014).
doi: 10.1038/cmi.2014.46
pubmed: 24954221
pmcid: 4220837
Timmons, B. C., Fairhurst, A. M. & Mahendroo, M. S. Temporal changes in myeloid cells in the cervix during pregnancy and parturition. J. Immunol. 182, 2700–2707. https://doi.org/10.4049/jimmunol.0803138 (2009).
doi: 10.4049/jimmunol.0803138
pubmed: 19234164
pmcid: 2752643
Rodriguez, H. A., Ortega, H. H., Ramos, J. G., Munoz-de-Toro, M. & Luque, E. H. Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response. Reprod. Biol. Endocrinol. 1, 113. https://doi.org/10.1186/1477-7827-1-113 (2003).
doi: 10.1186/1477-7827-1-113
pubmed: 14633278
pmcid: 305330
Shynlova, O. et al. Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling. J. Cell Mol. Med. 17, 311–324. https://doi.org/10.1111/jcmm.12012 (2013).
doi: 10.1111/jcmm.12012
pubmed: 23379349
pmcid: 3822594
Timmons, B. C. & Mahendroo, M. S. Timing of neutrophil activation and expression of proinflammatory markers do not support a role for neutrophils in cervical ripening in the mouse. Biol. Reprod. 74, 236–245. https://doi.org/10.1095/biolreprod.105.044891 (2006).
doi: 10.1095/biolreprod.105.044891
pubmed: 16237151
Brown, M. B., von Chamier, M., Allam, A. B. & Reyes, L. M1/M2 macrophage polarity in normal and complicated pregnancy. Front. Immunol. 5, 606. https://doi.org/10.3389/fimmu.2014.00606 (2014).
doi: 10.3389/fimmu.2014.00606
pubmed: 25505471
pmcid: 4241843
Egashira, M. et al. F4/80
doi: 10.1210/en.2016-1886
pubmed: 28525591
Yellon, S. M. Contributions to the dynamics of cervix remodeling prior to term and preterm birth. Biol. Reprod. 96, 13–23. https://doi.org/10.1095/biolreprod.116.142844 (2017).
doi: 10.1095/biolreprod.116.142844
pubmed: 28395330
Payne, K. J., Clyde, L. A., Weldon, A. J., Milford, T. A. & Yellon, S. M. Residency and activation of myeloid cells during remodeling of the prepartum murine cervix. Biol. Reprod. 87, 106. https://doi.org/10.1095/biolreprod.112.101840 (2012).
doi: 10.1095/biolreprod.112.101840
pubmed: 22914314
pmcid: 3509777
Zhang, Y. H., He, M., Wang, Y. & Liao, A. H. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front. Immunol. 8, 120. https://doi.org/10.3389/fimmu.2017.00120 (2017).
doi: 10.3389/fimmu.2017.00120
pubmed: 28232836
pmcid: 5299000
Zhang, L. et al. The inflammatory changes of adipose tissue in late pregnant mice. J. Mol. Endocrinol. 47, 157–165. https://doi.org/10.1530/JME-11-0030 (2011).
doi: 10.1530/JME-11-0030
pubmed: 21697073
pmcid: 3162642
Mackler, A. M., Iezza, G., Akin, M. R., McMillan, P. & Yellon, S. M. Macrophage trafficking in the uterus and cervix precedes parturition in the mouse. Biol. Reprod. 61, 879–883. https://doi.org/10.1095/biolreprod61.4.879 (1999).
doi: 10.1095/biolreprod61.4.879
pubmed: 10491619
Nadeau-Vallee, M. et al. Sterile inflammation and pregnancy complications: A review. Reproduction 152, R277–R292. https://doi.org/10.1530/REP-16-0453 (2016).
doi: 10.1530/REP-16-0453
pubmed: 27679863
Schaefer, L. Complexity of danger: The diverse nature of damage-associated molecular patterns. J. Biol. Chem. 289, 35237–35245. https://doi.org/10.1074/jbc.R114.619304 (2014).
doi: 10.1074/jbc.R114.619304
pubmed: 25391648
pmcid: 4271212
Frey, H., Schroeder, N., Manon-Jensen, T., Iozzo, R. V. & Schaefer, L. Biological interplay between proteoglycans and their innate immune receptors in inflammation. FEBS J. 280, 2165–2179. https://doi.org/10.1111/febs.12145 (2013).
doi: 10.1111/febs.12145
pubmed: 23350913
pmcid: 3651745
Wight, T. N. et al. Versican—A critical extracellular matrix regulator of immunity and inflammation. Front. Immunol. 11, 512. https://doi.org/10.3389/fimmu.2020.00512 (2020).
doi: 10.3389/fimmu.2020.00512
pubmed: 32265939
pmcid: 7105702
Couri, B. M. et al. Effect of pregnancy and delivery on cytokine expression in a mouse model of pelvic organ prolapse. Female Pelvic Med. Reconstr. Surg. 23, 449–456. https://doi.org/10.1097/SPV.0000000000000394 (2017).
doi: 10.1097/SPV.0000000000000394
pubmed: 28248847
pmcid: 5573670
Rosa, R. G. et al. Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes. Microsc. Res. Tech. 71, 169–178. https://doi.org/10.1002/jemt.20549 (2008).
doi: 10.1002/jemt.20549
pubmed: 18044701
Castelucci, B. G., Consonni, S. R., Rosa, V. S. & Joazeiro, P. P. Recruitment of monocytes and mature macrophages in mouse pubic symphysis relaxation during pregnancy and postpartum recovery. Biol. Reprod. 101, 466–477. https://doi.org/10.1093/biolre/ioz107 (2019).
doi: 10.1093/biolre/ioz107
pubmed: 31201427
pmcid: 6735965
Zhao, L. Mice without a functional relaxin gene are unable to deliver milk to their pups. Endocrinology 140, 445–453. https://doi.org/10.1210/endo.140.1.6404 (1999).
doi: 10.1210/endo.140.1.6404
pubmed: 9886856
Krajnc-Franken, M. A. et al. Impaired nipple development and parturition in LGR7 knockout mice. Mol. Cell Biol. 24, 687–696. https://doi.org/10.1128/mcb.24.2.687-696.2004 (2004).
doi: 10.1128/mcb.24.2.687-696.2004
pubmed: 14701741
pmcid: 343807
Kaftanovskaya, E. M., Huang, Z., Lopez, C., Conrad, K. & Agoulnik, A. I. Conditional deletion of the relaxin receptor gene in cells of smooth muscle lineage affects lower reproductive tract in pregnant mice. Biol. Reprod. 92, 91. https://doi.org/10.1095/biolreprod.114.127209 (2015).
doi: 10.1095/biolreprod.114.127209
pubmed: 25715795
pmcid: 4643956
Mi, Y. et al. Functional consequences of mannose and asialoglycoprotein receptor ablation. J. Biol. Chem. 291, 18700–18717. https://doi.org/10.1074/jbc.M116.738948 (2016).
doi: 10.1074/jbc.M116.738948
pubmed: 27405760
pmcid: 5009246
Mizejewski, G. J. The alpha-fetoprotein third domain receptor binding fragment: In search of scavenger and associated receptor targets. J. Drug Target 23, 538–551. https://doi.org/10.3109/1061186X.2015.1015538 (2015).
doi: 10.3109/1061186X.2015.1015538
pubmed: 25766080
Linck, G., Petrovic, A., Stoeckel, M. E. & Porte, A. Fine structure of the public symphysis in the mouse. Bull. Assoc. Anat. (Nancy) 60, 201–209 (1976).
Ricklin, D., Hajishengallis, G., Yang, K. & Lambris, J. D. Complement: A key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785–797. https://doi.org/10.1038/ni.1923 (2010).
doi: 10.1038/ni.1923
pubmed: 20720586
pmcid: 2924908
Chang, M. Y. et al. Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs. Am. J. Physiol. Lung Cell Mol. Physiol. 313, L1069–L1086. https://doi.org/10.1152/ajplung.00353.2017 (2017).
doi: 10.1152/ajplung.00353.2017
pubmed: 28912382
pmcid: 5814701
Barnett, F. H. et al. Macrophages form functional vascular mimicry channels in vivo. Sci. Rep. 6, 36659. https://doi.org/10.1038/srep36659 (2016).
doi: 10.1038/srep36659
pubmed: 27834402
pmcid: 5105153
Passi, A., Negrini, D., Albertini, R., Miserocchi, G. & De Luca, G. The sensitivity of versican from rabbit lung to gelatinase A (MMP-2) and B (MMP-9) and its involvement in the development of hydraulic lung edema. FEBS Lett. 456, 93–96. https://doi.org/10.1016/s0014-5793(99)00929-1 (1999).
doi: 10.1016/s0014-5793(99)00929-1
pubmed: 10452537
Gordon, S. & Taylor, P. R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953–964. https://doi.org/10.1038/nri1733 (2005).
doi: 10.1038/nri1733
pubmed: 16322748
Moro, C. F., Consonni, S. R., Rosa, R. G., Nascimento, M. A. & Joazeiro, P. P. High iNOS mRNA and protein localization during late pregnancy suggest a role for nitric oxide in mouse pubic symphysis relaxation. Mol. Reprod. Dev. 79, 272–282. https://doi.org/10.1002/mrd.22020 (2012).
doi: 10.1002/mrd.22020
pubmed: 22223460
Chang, M. Y. et al. Monocyte-to-macrophage differentiation: Synthesis and secretion of a complex extracellular matrix. J. Biol. Chem. 287, 14122–14135. https://doi.org/10.1074/jbc.M111.324988 (2012).
doi: 10.1074/jbc.M111.324988
pubmed: 22351750
pmcid: 3340194
Rayahin, J. E., Buhrman, J. S., Zhang, Y., Koh, T. J. & Gemeinhart, R. A. High and low molecular weight hyaluronic acid differentially influence macrophage activation. ACS Biomater. Sci. Eng. 1, 481–493. https://doi.org/10.1021/acsbiomaterials.5b00181 (2015).
doi: 10.1021/acsbiomaterials.5b00181
pubmed: 26280020
pmcid: 4533115
Schwabe, J., Donnelly, S. M., Jesmin, S., Leppert, P. & Mowa, C. N. A proteomic profile of cervical remodeling in mice during early and late pregnancy. J. Steroids Horm. Sci. 5, 1–9. https://doi.org/10.4172/2157-7536.1000123 (2014).
doi: 10.4172/2157-7536.1000123
Stanley, R. L., Ohashi, T., Gordon, J. & Mowa, C. N. A proteomic profile of postpartum cervical repair in mice. J. Mol. Endocrinol. 60, 17–28. https://doi.org/10.1530/JME-17-0179 (2018).
doi: 10.1530/JME-17-0179
pubmed: 29259042
Lutz, P. G., Houzel-Charavel, A., Moog-Lutz, C. & Cayre, Y. E. Myeloblastin is an Myb target gene: Mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid. Blood 97, 2449–2456. https://doi.org/10.1182/blood.v97.8.2449 (2001).
doi: 10.1182/blood.v97.8.2449
pubmed: 11290610
Klimiankou, M., Mellor-Heineke, S., Zeidler, C., Welte, K. & Skokowa, J. Role of CSF3R mutations in the pathomechanism of congenital neutropenia and secondary acute myeloid leukemia. Ann. N. Y. Acad. Sci. 1370, 119–125. https://doi.org/10.1111/nyas.13097 (2016).
doi: 10.1111/nyas.13097
pubmed: 27270496
Sharma, P., Sharma, A. & Srivastava, M. In vivo neutralization of alpha4 and beta7 integrins inhibits eosinophil trafficking and prevents lung injury during tropical pulmonary eosinophilia in mice. Eur. J. Immunol. 47, 1501–1512. https://doi.org/10.1002/eji.201747086 (2017).
doi: 10.1002/eji.201747086
pubmed: 28736941
Ortega-Gomez, A. et al. Cathepsin G controls arterial but not venular myeloid cell recruitment. Circulation 134, 1176–1188. https://doi.org/10.1161/CIRCULATIONAHA.116.024790 (2016).
doi: 10.1161/CIRCULATIONAHA.116.024790
pubmed: 27660294
pmcid: 5288007
Janssens, R., Struyf, S. & Proost, P. The unique structural and functional features of CXCL12. Cell Mol. Immunol. 15, 299–311. https://doi.org/10.1038/cmi.2017.107 (2018).
doi: 10.1038/cmi.2017.107
pubmed: 29082918
Girardi, G. Complement activation, a threat to pregnancy. Semin. Immunopathol. 40, 103–111. https://doi.org/10.1007/s00281-017-0645-x (2018).
doi: 10.1007/s00281-017-0645-x
pubmed: 28900713
Mastellos, D. C., Deangelis, R. A. & Lambris, J. D. Complement-triggered pathways orchestrate regenerative responses throughout phylogenesis. Semin. Immunol. 25, 29–38. https://doi.org/10.1016/j.smim.2013.04.002 (2013).
doi: 10.1016/j.smim.2013.04.002
pubmed: 23684626
pmcid: 3920450
Luo, C., Chen, M., Madden, A. & Xu, H. Expression of complement components and regulators by different subtypes of bone marrow-derived macrophages. Inflammation 35, 1448–1461. https://doi.org/10.1007/s10753-012-9458-1 (2012).
doi: 10.1007/s10753-012-9458-1
pubmed: 22450524
Modinger, Y., Loffler, B., Huber-Lang, M. & Ignatius, A. Complement involvement in bone homeostasis and bone disorders. Semin. Immunol. 37, 53–65. https://doi.org/10.1016/j.smim.2018.01.001 (2018).
doi: 10.1016/j.smim.2018.01.001
pubmed: 29395681
Stubelius, A. et al. Ncf1 affects osteoclast formation but is not critical for postmenopausal bone loss. BMC Musculoskelet. Disord. 17, 464. https://doi.org/10.1186/s12891-016-1315-1 (2016).
doi: 10.1186/s12891-016-1315-1
pubmed: 27829407
pmcid: 5103594
Kang, J. H., Sim, J. S., Zheng, T. & Yim, M. F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1%. J. Arch. Pharm. Res. 40, 492–499. https://doi.org/10.1007/s12272-017-0900-7 (2017).
doi: 10.1007/s12272-017-0900-7
Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement system part II: Role in immunity. Front. Immunol. 6, 257. https://doi.org/10.3389/fimmu.2015.00257 (2015).
doi: 10.3389/fimmu.2015.00257
pubmed: 26074922
pmcid: 4443744
Veridiano, A. M. et al. The mouse pubic symphysis as a remodeling system: Morphometrical analysis of proliferation and cell death during pregnancy, partus and postpartum. Cell Tissue Res. 330, 161–167. https://doi.org/10.1007/s00441-007-0463-x (2007).
doi: 10.1007/s00441-007-0463-x
pubmed: 17704950
Hong, Q., Kuo, E., Schultz, L., Boackle, R. J. & Chang, N. S. Conformationally altered hyaluronan restricts complement classical pathway activation by binding to C1q, C1r, C1s, C2, C5 and C9, and suppresses WOX1 expression in prostate DU145 cells. Int. J. Mol. Med. 19, 173–179 (2007).
pubmed: 17143562
Groeneveld, T. W. et al. Proteoglycans decorin and biglycan with C1q interactions of the extracellular matrix and collectins. J. Immunol. 175, 4715–4723. https://doi.org/10.4049/jimmunol.175.7.4715 (2005).
doi: 10.4049/jimmunol.175.7.4715
pubmed: 16177119
Fingleton, B. Matrix metalloproteinases as regulators of inflammatory processes. Biochim. Biophys. Acta Mol. Cell Res. 2036–2042, 2017. https://doi.org/10.1016/j.bbamcr.2017.05.010 (1864).
doi: 10.1016/j.bbamcr.2017.05.010
Bellac, C. L. et al. Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis. Cell Rep. 9, 618–632. https://doi.org/10.1016/j.celrep.2014.09.006 (2014).
doi: 10.1016/j.celrep.2014.09.006
pubmed: 25310974
Bennett, H. S., Wyrick, A. D., Lee, S. W. & McNeil, J. H. Science and art in preparing tissues embedded in plastic for light microscopy, with special reference to glycol methacrylate, glass knives and simple stains. Stain Technol. 51, 71–97 (1976).
doi: 10.3109/10520297609116677
Joazeiro, P. P., Consonni, S. R., Rosa, R. G. & Toledo, O. M. S. Pubic symphysis evaluation. In The Guide to Investigation of Mouse Pregnancy 1st edn (eds Croy, A., Yamada, A. T., DeMayo, F. J. & Adamson, S. L.) 733–749 (Elsevier, Amsterdam, 2014).
Bruni-Cardoso, A., Vilamaior, P. S., Taboga, S. R. & Carvalho, H. F. Localized matrix metalloproteinase (MMP)-2 and MMP-9 activity in the rat ventral prostate during the first week of postnatal development. Histochem. Cell Biol. 129, 805–815. https://doi.org/10.1007/s00418-008-0407-x (2008).
doi: 10.1007/s00418-008-0407-x
pubmed: 18320202
Silva, J. C. et al. Quantitative proteomic analysis by accurate mass retention time pairs. Anal. Chem. 77, 2187–2200. https://doi.org/10.1021/ac048455k (2005).
doi: 10.1021/ac048455k
pubmed: 15801753
Conover, W. J. & Iman, R. L. Rank transformations as a bridge between parametric and nonparametric statistics. Am. Stat. 35, 124–129 (1981).
Montgomery, D. C. Design and Analysis of Experiments 3rd edn. (Wiley, New York, 1991).