Proceedings of The Physiological Society

Obesity (2014) Proc Physiol Soc 32, PC006

Poster Communications

The effects of a high-fat, high-cholesterol (HFHC) diet on uterine contractile protein expression and ex-vivo contractile activity in term pregnant rats

R. Muir1, B. Clifford1, S. McMullen1, K. Raheela2, S. Quenby3,4, A. Shmygol3, M. J. Elmes1

1. Biosciences, Nutritional Sciences, University of Nottingham, Loughborough, Leicestershire, United Kingdom. 2. Graduate School of Medicine,, University of Nottingham, Derby, Derbyshire, United Kingdom. 3. Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick,, Coventry, Warwickshire, United Kingdom. 4. Biomedical Research Unit in Reproductive Health,, University Hospital Coventry and Warwickshire, Covenrty, Warwickshire, United Kingdom.

The prevalence of maternal obesity is increasing and is associated with uterine contractile dysfunction and emergency caesarean section. The mechanisms through which maternal obesity causes uterine dysfunction are currently unknown. A recent pilot study feeding rats a HFHC diet to induce obesity illustrated negative effects upon uterine contractile associated protein (CAP) expression during labour. This study's aim was to determine whether a HFHC diet has adverse effects on ex vivo uterine contractility and uterine CAP expression in term non-labouring (TNL) and term labouring animals (TL). All animal research was approved by the UK Home Office and carried out under ASPA 1986. 40 female Wistar rats were fed either a control chow (CON n=20) or HFHC (n=20) diet for 6 weeks. Rats were then mated, and maintained on their respective diet throughout pregnancy until day 21 TNL (n=10) or day 22 TL (1st pup delivery) (n=10) and euthanized. Uterine tissue was snap frozen for western blot analysis of CAPs Caveolin-1 (CAV1) & Connexin-43 (CX43). Uterine strips were also dissected and mounted within an organ bath to equilibrate prior to 30 minutes baseline recording of spontaneous contractile activity. Statistical tests using SPSS included independent t test for determination of visceral fat levels and CAP expression and One-way ANOVA for the variation in individual spontaneous myometrial contractions all at the P<0.05 level. HFHC fed rats had significantly greater fat mass, 24.19g ± 2.29, versus 12.73g ± 0.99 for CON, P< 0.05). The HFHC diet significantly increased CAV1 expression in TNL tissue compared to CON (P<0.03), however no difference was observed in TL samples. Uterine CAV1 expression significantly decreased (P = 0.007) from TNL to TL within HFHC animals, but no significant change was observed in CON animals. CX43 expression in TNL tissue was significantly higher in HFHC versus CON animals (P<0.047), CX43 expression was lower in TL animals but not to statistical significance (P<0.078). Within dietary groups, CX43 expression was significantly up-regulated with TL in CON rats (P<0.001), however, up-regulation of CX43 with TL was absent in HFHC fed rats. Analysis of baseline spontaneous uterine contractile activity identified a lack of synchronous contractions within the HFHC fed animals compared to CON (Fig.1). Variation in the amplitude of uterine contractions in CON animals improved significantly from TNL to TL (P<0.012). In contrast, rats fed the HFHC diet displayed asynchronous contractile activity at TNL. There was improvement with TL but asynchronous activity persisted. In conclusion HFHC diet induced obesity negatively affects synchronisation of uterine contractions at term. This asynchronous contractile phenotype may result from adverse effects of obesity on uterine CAP expression.

Where applicable, experiments conform with Society ethical requirements