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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

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 - http://dx.doi.org/10.1071/RD13372
Submitted: 4 November 2013  Accepted: 9 February 2014   Published online: 17 March 2014


 
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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.


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