Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Follistatin is essential for normal postnatal development and function of mouse oviduct and uterus

S. J. Holdsworth-Carson A , R. G. Craythorn B , W. R. Winnall C , K. Dhaliwal B , R. Genovese B , C. J. Nowell D , P. A. W. Rogers A , D. M. de Kretser B , M. P. Hedger B and J. E. Girling A B E
+ Author Affiliations
- Author Affiliations

A University of Melbourne Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Parkville, Vic. 3052, Australia.

B Monash Institute of Medical Research, Monash University, Clayton, Vic. 3168, Australia.

C Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic. 3010, Australia.

D Ludwig Institute for Cancer Research, Melbourne – Parkville Branch, Vic. 3052, Australia.

E Corresponding author. Email: jgirling@unimelb.edu.au

Reproduction, Fertility and Development 27(7) 985-999 https://doi.org/10.1071/RD13372
Submitted: 4 November 2013  Accepted: 9 February 2014   Published: 17 March 2014

Abstract

Female mice lacking the follistatin gene but expressing a human follistatin-315 transgene (tghFST315) have reproductive abnormalities (reduced follicles, no corpora lutea and ovarian–uterine inflammation). We hypothesised that the absence of follistatin-288 causes the abnormal reproductive tract via both developmental abnormalities and abnormal ovarian activity. We characterised the morphology of oviducts and uteri in wild type (WT), tghFST315 and follistatin-knockout mice expressing human follistatin-288 (tghFST288). The oviducts and uteri were examined in postnatal Day-0 and adult mice (WT and tghFST315 only) using histology and immunohistochemistry. Adult WT and tghFST315 mice were ovariectomised and treated with vehicle, oestradiol-17β (100 ng injection, dissection 24 h later) or progesterone (1 mg × three daily injections, dissection 24 h later). No differences were observed in the oviducts or uteri at birth, but abnormalities developed by adulthood. Oviducts of tghFST315 mice failed to coil, the myometrium was disorganised, endometrial gland number was reduced and oviducts and uteri contained abundant leukocytes. After ovariectomy, tghFST315 mice had altered uterine cell proliferation, and inflammation was maintained and exacerbated by oestrogen. These studies show that follistatin is crucial to postnatal oviductal–uterine development and function. Further studies differentiating the role of ovarian versus oviductal–uterine follistatin in reproductive tract function at different developmental stages are warranted.

Additional keywords: activin A, inflammation, Müllerian duct, myometrium, oestrogen.


References

Branham, W. S., and Sheehan, D. M. (1995). Ovarian and adrenal contributions to postnatal growth and differentiation of the rat uterus. Biol. Reprod. 53, 863–872.
Ovarian and adrenal contributions to postnatal growth and differentiation of the rat uterus.CrossRef | 1:CAS:528:DyaK2MXotFyju7k%3D&md5=5dd0a174f07b5130eb460cc24dde61d2CAS | 8547482PubMed |

Branham, W. S., Sheehan, D. M., Zehr, D. R., Ridlon, E., and Nelson, C. J. (1985). The postnatal ontogeny of rat uterine glands and age-related effects of 17 beta-oestradiol. Endocrinology 117, 2229–2237.
The postnatal ontogeny of rat uterine glands and age-related effects of 17 beta-oestradiol.CrossRef | 1:CAS:528:DyaL2MXmtVKqsrc%3D&md5=6b6f68bdd5c66e6498f72a4ecddba234CAS | 4042984PubMed |

Brody, J. R., and Cunha, G. R. (1989). Histologic, morphometric and immunocytochemical analysis of myometrial development in rats and mice. 1. Normal development. Am. J. Anat. 186, 1–20.
Histologic, morphometric and immunocytochemical analysis of myometrial development in rats and mice. 1. Normal development.CrossRef | 1:STN:280:DyaL1MzptVequg%3D%3D&md5=8aa378ed0ac7e21765cbe9155afa23f5CAS | 2782286PubMed |

Ciarmela, P., Wiater, E., and Vale, W. (2008). Activin-A in myometrium: characterisation of the actions on myometrial cells. Endocrinology 149, 2506–2516.
Activin-A in myometrium: characterisation of the actions on myometrial cells.CrossRef | 1:CAS:528:DC%2BD1cXht1GmsLfL&md5=a8d4216db0781a8caf60c3654f415967CAS | 18239071PubMed |

Craythorn, R. G., Girling, J. E., Hedger, M. P., Rogers, P. A., and Winnall, W. R. (2009). An RNA-spiking method demonstrates that 18S rRNA is regulated by progesterone in the mouse uterus. Mol. Hum. Reprod. 15, 757–761.
An RNA-spiking method demonstrates that 18S rRNA is regulated by progesterone in the mouse uterus.CrossRef | 1:CAS:528:DC%2BD1MXht1Ortr%2FJ&md5=d039aa2c949577e90001fb41f325979cCAS | 19602508PubMed |

Craythorn, R. G., Winnall, W. R., Lederman, F., Gold, E. J., O’Connor, A. E., de Kretser, D. M., Hedger, M. P., Rogers, P. A., and Girling, J. E. (2012). Progesterone stimulates expression of follistatin splice variants Fst288 and Fst315 in the mouse uterus. Reprod. Biomed. Online 24, 364–374.
Progesterone stimulates expression of follistatin splice variants Fst288 and Fst315 in the mouse uterus.CrossRef | 1:CAS:528:DC%2BC38Xjt1ehsb8%3D&md5=9a089326642f58d02701c3f8277236f6CAS | 22285243PubMed |

de Kretser, D. M., Hedger, M. P., and Phillips, D. J. (1999). Activin A and follistatin: their role in the acute-phase reaction and inflammation. J. Endocrinol. 161, 195–198.
Activin A and follistatin: their role in the acute-phase reaction and inflammation.CrossRef | 1:CAS:528:DyaK1MXjs12kt7o%3D&md5=bc0d3b999aa52abcf9671dde7ddb533aCAS | 10320816PubMed |

de Kretser, D. M., O’Hehir, R. E., Hardy, C. L., and Hedger, M. P. (2012). The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Mol. Cell. Endocrinol. 359, 101–106.
The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair.CrossRef | 1:CAS:528:DC%2BC38XnslOhsLY%3D&md5=f183f340079067b010012ae37ebf062bCAS | 22037168PubMed |

Feijen, A., Goumans, M. J., and van den Eijnden-van Raaij, A. J. (1994). Expression of activin subunits, activin receptors and follistatin in post-implantation mouse embryos suggests specific developmental functions for different activins. Development 120, 3621–3637.
| 1:CAS:528:DyaK2MXislWksbc%3D&md5=255adb8a6f54266cc03f4e5cb4a17a09CAS | 7821227PubMed |

Girling, J. E., Lederman, F. L., Walter, L. M., and Rogers, P. A. (2007). Progesterone, but not oestrogen, stimulates vessel maturation in the mouse endometrium. Endocrinology 148, 5433–5441.
Progesterone, but not oestrogen, stimulates vessel maturation in the mouse endometrium.CrossRef | 1:CAS:528:DC%2BD2sXht1aju7bF&md5=c74ec978e17d71adb5d85d015d45eeb2CAS | 17690161PubMed |

Guo, Q., Kumar, T. R., Woodruff, T., Hadsell, L. A., DeMayo, F. J., and Matzuk, M. M. (1998). Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Mol. Endocrinol. 12, 96–106.
Overexpression of mouse follistatin causes reproductive defects in transgenic mice.CrossRef | 1:CAS:528:DyaK1cXhvFWgsA%3D%3D&md5=cc7ab8c9b68b563c6c5241de899800a2CAS | 9440814PubMed |

Hashimoto, O., Nakamura, T., Shoji, H., Shimasaki, S., Hayashi, Y., and Sugino, H. (1997). A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells. Endocytotic degradation of activin and its acceleration by follistatin associated with cell-surface heparan sulfate. J. Biol. Chem. 272, 13 835–13 842.
A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells. Endocytotic degradation of activin and its acceleration by follistatin associated with cell-surface heparan sulfate.CrossRef | 1:CAS:528:DyaK2sXjsFWht78%3D&md5=eaf8cbb2ee03eeed302e5873db61e4f4CAS |

Hayashi, K., Carpenter, K. D., Gray, C. A., and Spencer, T. E. (2003). The activin–follistatin system in the neonatal ovine uterus. Biol. Reprod. 69, 843–850.
The activin–follistatin system in the neonatal ovine uterus.CrossRef | 1:CAS:528:DC%2BD3sXmvVeitLs%3D&md5=f778b70745ca0bdd56a5fb6878dd53d7CAS | 12748120PubMed |

Hedger, M. P., Winnall, W. R., Phillips, D. J., and de Kretser, D. M. (2011). The regulation and functions of activin and follistatin in inflammation and immunity. Vitam. Horm. 85, 255–297.
The regulation and functions of activin and follistatin in inflammation and immunity.CrossRef | 1:CAS:528:DC%2BC3MXovVCit7g%3D&md5=f73228dd16d1452311cd98124c19292fCAS | 21353885PubMed |

Heryanto, B., and Rogers, P. A. W. (2002). Regulation of endometrial endothelial cell proliferation by oestrogen and progesterone in the ovariectomised mouse. Reproduction 123, 107–113.
Regulation of endometrial endothelial cell proliferation by oestrogen and progesterone in the ovariectomised mouse.CrossRef | 1:CAS:528:DC%2BD38XhtV2gsL4%3D&md5=0962908065fb03afb0d0c8fc539f4c0aCAS | 11869192PubMed |

Hunt, J. S. (1994). Immunologically relevant cells in the uterus. Biol. Reprod. 50, 461–466.
Immunologically relevant cells in the uterus.CrossRef | 1:STN:280:DyaK2c3itVGlsg%3D%3D&md5=b59dd36af7d7b5a3bd7b6086b1b74bc9CAS | 8167216PubMed |

Jones, R. L., Salamonsen, L. A., and Findlay, J. K. (2002a). Activin A promotes human endometrial stromal cell decidualisation in vitro. J. Clin. Endocrinol. Metab. 87, 4001–4004.
Activin A promotes human endometrial stromal cell decidualisation in vitro.CrossRef | 1:CAS:528:DC%2BD38XmtF2gu70%3D&md5=fda7c72cba978a3d4de5f1d12f300aa6CAS | 12161551PubMed |

Jones, R. L., Salamonsen, L. A., and Findlay, J. K. (2002b). Potential roles for endometrial inhibins, activins and follistatin during human embryo implantation and early pregnancy. Trends Endocrinol. Metab. 13, 144–150.
Potential roles for endometrial inhibins, activins and follistatin during human embryo implantation and early pregnancy.CrossRef | 1:CAS:528:DC%2BD38Xjs1Kmt7k%3D&md5=950fc7c45f49bb38301bbb15e95930caCAS | 11943557PubMed |

Jones, K. L., Mansell, A., Patella, S., Scott, B. J., Hedger, M. P., de Kretser, D. M., and Phillips, D. J. (2007). Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. Proc. Natl. Acad. Sci. USA 104, 16 239–16 244.
Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia.CrossRef | 1:CAS:528:DC%2BD2sXhtF2gsr7L&md5=41fd2b97a5e91aa28792c5b6198481ffCAS |

Jorgez, C. J., Klysik, M., Jamin, S. P., Behringer, R. R., and Matzuk, M. M. (2004). Granulosa cell-specific inactivation of follistatin causes female fertility defects. Mol. Endocrinol. 18, 953–967.
Granulosa cell-specific inactivation of follistatin causes female fertility defects.CrossRef | 1:CAS:528:DC%2BD2cXivFGjsbk%3D&md5=138cef140737c261826b10bc26fc1597CAS | 14701941PubMed |

Kachkache, M., Acker, G. M., Chaouat, G., Noun, A., and Garabedian, M. (1991). Hormonal and local factors control the immunohistochemical distribution of immunocytes in the rat uterus before conceptus implantation – effects of ovariectomy, fallopian-tube section and injection. Biol. Reprod. 45, 860–868.
Hormonal and local factors control the immunohistochemical distribution of immunocytes in the rat uterus before conceptus implantation – effects of ovariectomy, fallopian-tube section and injection.CrossRef | 1:STN:280:DyaK383hsF2lsg%3D%3D&md5=12aeecbe6e957d1a09b1565c103bfc66CAS | 1805988PubMed |

Katayama, S., Ashizawa, K., Fukuhara, T., Hiroyasu, M., Tsuzuki, Y., Tatemoto, H., Nakada, T., and Nagai, K. (2006). Differential expression patterns of Wnt and β-Catenin/TCF target genes in the uterus of immature female rats exposed to 17α-ethynyl oestradiol. Toxicol. Sci. 91, 419–430.
Differential expression patterns of Wnt and β-Catenin/TCF target genes in the uterus of immature female rats exposed to 17α-ethynyl oestradiol.CrossRef | 1:CAS:528:DC%2BD28XkvVSkurk%3D&md5=f91683ef582ff510537e8cfd647dfc88CAS | 16551644PubMed |

Kimura, F., Sidis, Y., Bonomi, L., Xia, Y., and Schneyer, A. (2010). The follistatin-288 isoform alone is sufficient for survival but not for normal fertility in mice. Endocrinology 151, 1310–1319.
The follistatin-288 isoform alone is sufficient for survival but not for normal fertility in mice.CrossRef | 1:CAS:528:DC%2BC3cXjvVKqtL4%3D&md5=ce6b2aaa2cc0a0b57e49fb5210de52a1CAS | 20032047PubMed |

Knight, P. G., Satchell, L., and Glister, C. (2012). Intra-ovarian roles of activins and inhibins. Mol. Cell. Endocrinol. 359, 53–65.
Intra-ovarian roles of activins and inhibins.CrossRef | 1:CAS:528:DC%2BC38XnslOjurw%3D&md5=1a00bb93aeaae5b5e632c9013d9b4494CAS | 21664422PubMed |

Lerch, T. F., Shimasaki, S., Woodruff, T. K., and Jardetzky, T. S. (2007). Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions. J. Biol. Chem. 282, 15 930–15 939.
Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions.CrossRef | 1:CAS:528:DC%2BD2sXltl2nsLc%3D&md5=24ebc258fa3a15088fc5d3718a8dbd4bCAS |

Li, Q., Agno, J. E., Edson, M. A., Nagaraja, A. K., Nagashima, T., and Matzuk, M. M. (2011). Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function. PLoS Genet. 7, e1002320.
Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function.CrossRef | 1:CAS:528:DC%2BC3MXhsVCku7jK&md5=99b58274982b591a4e175bf4121d497cCAS | 22028666PubMed |

Lin, S. Y., Craythorn, R. G., O’Connor, A. E., Matzuk, M. M., Girling, J. E., Morrison, J. R., and de Kretser, D. M. (2008). Female infertility and disrupted angiogenesis are actions of specific follistatin isoforms. Mol. Endocrinol. 22, 415–429.
Female infertility and disrupted angiogenesis are actions of specific follistatin isoforms.CrossRef | 1:CAS:528:DC%2BD1cXhtlWiu7o%3D&md5=4fe1b1b86ad49c2f28accf2517fc6b9bCAS | 17932109PubMed |

Lydon, J. P., DeMayo, F. J., Conneely, O. M., and O’Malley, B. W. (1996). Reproductive phenotypes of the progesterone receptor null mutant mouse. The Journal of Steroid Biochemistry and Molecular Biology 56, 67–77.
Reproductive phenotypes of the progesterone receptor null mutant mouse.CrossRef | 1:CAS:528:DyaK28XitVeqt78%3D&md5=4e526d322d5f30d879e0efcc7017e80dCAS | 8603049PubMed |

Marcondes, F. K., Bianchi, F. J., and Tanno, A. P. (2002). Determination of the oestrous cycle phases of rats: some helpful considerations. Braz. J. Biol. 62, 609–614.
Determination of the oestrous cycle phases of rats: some helpful considerations.CrossRef | 1:STN:280:DC%2BD3s7ksValsA%3D%3D&md5=2079ebd488edc11b242aafb04c994fd7CAS | 12659010PubMed |

Massé, J., Watrin, T., Laurent, A., Deschamps, S., Guerrier, D., and Pellerin, I. (2009). The developing female genital tract: from genetics to epigenetics Int. J. Dev. Biol. 53, 411–424.
The developing female genital tract: from genetics to epigeneticsCrossRef | 19412895PubMed |

Matzuk, M. M., Lu, N., Vogel, H., Sellheyer, K., Roop, D. R., and Bradley, A. (1995). Multiple defects and perinatal death in mice deficient in follistatin. Nature 374, 360–363.
Multiple defects and perinatal death in mice deficient in follistatin.CrossRef | 1:CAS:528:DyaK2MXksFKnu7c%3D&md5=590cba7471135da89cebbf1866697ba1CAS | 7885475PubMed |

Mercado, M., Shimasaki, S., Ling, N., and DePaolo, L. (1993). Effects of oestrous cycle stage and pregnancy on follistatin gene expression and immunoreactivity in rat reproductive tissues: progesterone is implicated in regulating uterine gene expression. Endocrinology 132, 1774–1781.
| 1:CAS:528:DyaK3sXisVOqt7g%3D&md5=0d8006478ae580fff7fbe69154ca304dCAS | 8462476PubMed |

Nakamura, T., Takio, K., Eto, Y., Shibai, H., Titani, K., and Sugino, H. (1990). Activin-binding protein from rat ovary is follistatin. Science 247, 836–838.
Activin-binding protein from rat ovary is follistatin.CrossRef | 1:CAS:528:DyaK3cXhsFajsbg%3D&md5=82b967a85f7d37fd400116231ccacb3fCAS | 2106159PubMed |

O’Connor, A. E., McFarlane, J. R., Hayward, S., Yohkaichiya, T., Groome, N. P., and de Kretser, D. M. (1999). Serum activin A and follistatin concentrations during human pregnancy: a cross-sectional and longitudinal study. Hum. Reprod. 14, 827–832.
Serum activin A and follistatin concentrations during human pregnancy: a cross-sectional and longitudinal study.CrossRef | 1:CAS:528:DyaK1MXisV2qtr0%3D&md5=5b59ee202a11bedbecf3d1583b9dbc50CAS | 10221721PubMed |

Patel, K. (1998). Follistatin. Int. J. Biochem. Cell Biol. 30, 1087–1093.
Follistatin.CrossRef | 1:CAS:528:DyaK1cXmsVynsrs%3D&md5=e676de26214603830145c727f717d527CAS | 9785474PubMed |

Petraglia, F., Gallinelli, A., Grande, A., Florio, P., Ferrari, S., Genazzani, A. R., Ling, N., and DePaolo, L. V. (1994). Local production and action of follistatin in human placenta. J. Clin. Endocrinol. Metab. 78, 205–210.
| 1:CAS:528:DyaK2cXht1Ghsr4%3D&md5=d4638448eaddca12b63d2782a48bb622CAS | 8288705PubMed |

Pfaffl, M. W. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45.
A new mathematical model for relative quantification in real-time RT-PCR.CrossRef | 1:STN:280:DC%2BD38nis12jtw%3D%3D&md5=a85f664bc260399bf368abd364128362CAS | 11328886PubMed |

Refaat, B., and Ledger, W. (2011). The expression of activins, their type II receptors and follistatin in human Fallopian tube during the menstrual cycle and in pseudo-pregnancy. Hum. Reprod. 26, 3346–3354.
The expression of activins, their type II receptors and follistatin in human Fallopian tube during the menstrual cycle and in pseudo-pregnancy.CrossRef | 1:CAS:528:DC%2BC3MXhsVymtb7K&md5=21036174c643c0cc89adad4b2a04e9d3CAS | 21984573PubMed |

Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., Tinevez, J. Y., White, D. J., Hartenstein, V., Eliceiri, K., Tomancak, P., and Cardona, A. (2012). Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682.
Fiji: an open-source platform for biological-image analysis.CrossRef | 1:CAS:528:DC%2BC38XhtVKnurbJ&md5=5b0973c97ee537ca03e965b9bafba031CAS | 22743772PubMed |

Shiorta, M., Kawashima, J., Nakamura, T., Ogawa, Y., Kamiie, J., Yasuno, K., Shirota, K., and Yoshida, M. (2012). Delayed effects of single neonatal subcutaneous exposure of low-dose 17alpha-ethynylestradiol on reproductive function in female rats. J. Toxicol. Sci. 37, 681–690.
Delayed effects of single neonatal subcutaneous exposure of low-dose 17alpha-ethynylestradiol on reproductive function in female rats.CrossRef | 1:CAS:528:DC%2BC38XhsVOhtb3O&md5=11c4ad7b5f69171bc8e8bf0d0ac91d9dCAS | 22863849PubMed |

Spencer, T. E., Dunlap, K. A., and Filant, J. (2012). Comparative developmental biology of the uterus: insights into mechanisms and developmental disruption. Mol. Cell. Endocrinol. 354, 34–53.
Comparative developmental biology of the uterus: insights into mechanisms and developmental disruption.CrossRef | 1:CAS:528:DC%2BC38Xjslentb4%3D&md5=b2340aba92e6a81806ec92b09881c300CAS | 22008458PubMed |

Stewart, C. A., and Behringer, R. R. (2012) Mouse oviduct development. In ‘Mouse Development, Results and Problems in Cell Differentation. Vol. 55’. (Ed. J. Z. Kubiak) pp. 247–262. (Springer-Verlag: Berling Heidelberg.)

Sugino, K., Kurosawa, N., Nakamura, T., Takio, K., Shimasaki, S., Ling, N., Titani, K., and Sugino, H. (1993). Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell. J. Biol. Chem. 268, 15 579–15 587.
| 1:CAS:528:DyaK3sXmtFOmu7w%3D&md5=e75253d66c65fc5e3387f07efb69f77dCAS |

Tibbetts, T. A., Conneely, O. M., and O’Malley, B. W. (1999). Progesterone via its receptor antagonises the pro-inflammatory activity of oestrogen in the mouse uterus. Biol. Reprod. 60, 1158–1165.
Progesterone via its receptor antagonises the pro-inflammatory activity of oestrogen in the mouse uterus.CrossRef | 1:CAS:528:DyaK1MXislegtLg%3D&md5=8c28048ef47b4499444f0aa03a52864aCAS | 10208978PubMed |

Tierney, E. P., and Giudice, L. C. (2004). Role of activin A as a mediator of in vitro endometrial stromal cell decidualisation via the cyclic adenosine monophosphate pathway. Fertil. Steril. 81, 899–903.
| 1:CAS:528:DC%2BD2MXitFGhsLc%3D&md5=832436462c14baee2a737c8c25afd947CAS | 15019827PubMed |

Tomaszewski, J., Joseph, A., Archambeault, D., and Yao, H. H.-C. (2007). Essential roles of inhibin beta A in mouse epididymal coiling. Proc. Natl. Acad. Sci. USA 104, 11 322–11 327.
Essential roles of inhibin beta A in mouse epididymal coiling.CrossRef | 1:CAS:528:DC%2BD2sXnvFOmsr4%3D&md5=0f999abfaee532aa0f93278196d360b3CAS |

Walter, L. M., Rogers, P. A. W., and Girling, J. E. (2005). The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice. Reproduction 129, 765–777.
The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice.CrossRef | 1:CAS:528:DC%2BD2MXlvFGit70%3D&md5=999f2623a7b8d952e531b044d8b78984CAS | 15923392PubMed |

Walter, L. M., Rogers, P. A. W., and Girling, J. E. (2010). Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus. Reproduction 140, 331–341.
Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus.CrossRef | 1:CAS:528:DC%2BC3cXhtFensr7N&md5=32d0b44cfce94ea09b0ace26b340624cCAS | 20530092PubMed |

Wankell, M., Munz, B., Hubner, G., Hans, W., Wolf, E., Goppelt, A., and Werner, S. (2001). Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J. 20, 5361–5372.
Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis.CrossRef | 1:CAS:528:DC%2BD38XjtVSqsA%3D%3D&md5=c822bbffef39a2602024319869b5ddf7CAS | 11574468PubMed |

Winnall, W. R., Muir, J. A., Liew, S., Hirst, J. J., Meachem, S. J., and Hedger, M. P. (2009). Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-treated rats. Int. J. Androl. 32, 542–555.
Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-treated rats.CrossRef | 1:CAS:528:DC%2BD1MXht1OqsbbP&md5=d070ebdfa9142d7702c24d8b54785c58CAS | 18522674PubMed |

Winnall, W. R., Muir, J. A., and Hedger, M. P. (2011). Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro. J. Leukoc. Biol. 90, 133–143.
Rat resident testicular macrophages have an alternatively activated phenotype and constitutively produce interleukin-10 in vitro.CrossRef | 1:CAS:528:DC%2BC3MXptFyqs7s%3D&md5=ca4a6965fb793c8c90982255613fd1bdCAS | 21498587PubMed |

Wu, H., Chen, Y., Winnall, W. R., Phillips, D. J., and Hedger, M. P. (2012). Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 303, R665–R675.
Acute regulation of activin A and its binding protein, follistatin, in serum and tissues following lipopolysaccharide treatment of adult male mice.CrossRef | 1:CAS:528:DC%2BC38XhsFKktbfF&md5=3c40ac42e64d5c607166ab19d1ac435dCAS | 22855279PubMed |

Wu, H., Chen, Y., Winnall, W. R., Phillips, D. J., and Hedger, M. P. (2013). Regulation of activin A release from murine bone marrow-derived neutrophil precursors by tumour necrosis factor-α and insulin. Cytokine 61, 199–204.
Regulation of activin A release from murine bone marrow-derived neutrophil precursors by tumour necrosis factor-α and insulin.CrossRef | 1:CAS:528:DC%2BC38XhsFymurjL&md5=83381a8ef6e1e9d9df21c1903b04b2bfCAS | 23116663PubMed |

Yao, H. H., Matzuk, M. M., Jorgez, C. J., Menke, D. B., Page, D. C., Swain, A., and Capel, B. (2004). Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis. Dev. Dyn. 230, 210–215.
Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis.CrossRef | 1:CAS:528:DC%2BD2cXltFymt78%3D&md5=d94a24a52abc82986078a0ed3d953c43CAS | 15162500PubMed |


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