Abstract
Increasing levels of obesity within women of reproductive age is a major concern in the UK. Approximately, 13% of women aged <30 and 22% of 31- to 40-year-old women are obese. Obesity increases complications during pregnancy and the risk of caesarean section due to prolonged labour and poor uterine activity. The aim was to investigate whether a high-fat, high-cholesterol (HFHC) diet decreases markers of uterine contractility during parturition in the rat. Female Wistar rats were fed control (CON, n=10) or HFHC (n=10) diets for 6 weeks. Animals were mated and, once pregnant, maintained on their diet throughout gestation. On gestational day 19, rats were monitored continuously and killed at the onset of parturition. Body and fat depot weights were recorded. Myometrial tissue was analysed for cholesterol (CHOL), triglycerides (TAG), and expression of the contractile associated proteins gap junction protein alpha 1 (GJA1; also known as connexin-43, CX-43), prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclo-oxygenase-2, COX-2) and caveolin-1 (CAV1) and maternal plasma for prostaglandin F(2)(α) (PGF(2)(α)) and progesterone. HFHC fed rats gained greater weight than CON (P<0.003) with significant increases in peri-renal fat (P<0.01). The HFHC diet increased plasma CHOL, TAG and progesterone, but decreased PGF(2)(α) versus CON (P<0.01, P<0.01, P=0.05 and P<0.02 respectively). Total CHOL and TAG levels of uterine tissue were similar. However, HFHC fed rats showed significant increases in PTGS2 (P<0.037), but decreases in GJA1 and CAV1 (P=0.059). In conclusion, a HFHC diet significantly increases body weight and alters lipid profiles that correlate with decreases in key markers of uterine contractility. Further work is required to ascertain whether these changes have adverse effects on uterine activity.
Highlights
Obesity is a major public health concern, and its prevalence in women of reproductive age is increasing globally (WHO 2000)
Uterine contractile activity is regulated by the key proteins caveolin-1 (CAV1), gap junction protein alpha 1 (GJA1; known as connexin-43, CX-43) and prostaglandin-endoperoxide synthase 2 (PTGS2; known as cyclooxygenase-2, COX-2)
This study was the first to utilise a rat model to assess the effects of a HFHC diet on maternal lipid profiles and markers of uterine activity during parturition
Summary
Obesity is a major public health concern, and its prevalence in women of reproductive age is increasing globally (WHO 2000). Ex vivo manipulation of myometrial CHOL content reveals that decreasing and increasing CHOL q 2011 Society for Reproduction and Fertility ISSN 1470–1626 (paper) 1741–7899 (online) increases and decreases the strength of myometrial contractions respectively, suggesting that high circulatory CHOL seen in many obese women could impair uterine activity during labour (Smith et al 2005). Three different isoforms exist (CAV1–3; Okamoto et al 1998), CAV1 controls activity of transduction pathways as Cav knockout mice exhibit impaired smooth muscle (aortic ring) vascular relaxation (Drab et al 2001), and CHOL extraction reduces caveolae number increasing contractility of both human and rodent myometrium (Noble et al 2006).
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