222. A new role for activin in endometrial restoration after menses
T. J. Kaitu’u-Lino A B , D. J. Phillips C , N. B. Morison B and L. A. Salamonsen BA Centre for Women's Health Research, Monash Institue of Medical Research, Monash University, Clayton, Vic., Australia.
B Prince Henry's Institute, Clayton, Vic., Australia.
C Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, Vic., Australia.
Reproduction, Fertility and Development 20(9) 22-22 https://doi.org/10.1071/SRB08Abs222
Published: 28 August 2008
Abstract
10% of Australian women suffer from abnormal uterine bleeding (AUB). To stop endometrial bleeding after menstruation, the endometrium must repair adequately. We propose that endometrial restoration after menstruation has characteristics of wound healing and that inadequate endometrial repair may result in AUB. In vivo studies support a contribution of activins to skin wound healing: in mice overexpressing activins' natural inhibitor, follistatin, wound healing is significantly delayed (1). We hypothesised that activin would enhance endometrial repair and examined its contribution using an in vitro wound healing model and our well characterised in vivo mouse model of endometrial breakdown and repair (2). For the in vitro model, confluent human endometrial epithelial cells (ECC-1 cell line) were wounded and treated with carrier protein (control, 0.1% BSA), activin A (50ng/mL) or EGF (positive control: 50ng/mL). Wound areas were quantitated daily for 6 days. For the in vivo study, serum follistatin levels were measured by ELISA in follistatin overexpressing mice (FS) (2) and wild-type (WT) littermates. Mice were induced to undergo endometrial breakdown and repair (mimicking menstruation in women). Activin βA was immunolocalised during endometrial repair, and extent of repair assessed using our morphological scoring system (2). ECC-1 wound repair was significantly (P < 0.05) enhanced by activin A treatment v. control from days 2–6 of culture. In WT mice, activin βA localised to areas of endometrial repair. Serum follistatin was significantly elevated in FS mice v. controls (33.3 ± 3.8 v 7.07 ± 1.8 ng/mL, P < 0.01). In FS mice (n = 8) only 50% of uterine sections showed complete repair after endometrial breakdown, significantly less than those from WT animals (n = 15, P < 0.05) where 85% of sections demonstrated complete repair. These results demonstrate for the first time that activin A functions to promote endometrial restoration following menses and that this can be delayed under physiological conditions: such studies indicate potential treatments for AUB.
(1) Wankell et al. (2001) EMBO J 20:5361–5372
(2) Kaitu'u-Lino et al. (2007) Endocrinology 148:5105–5111
