The effects of a high-fat, high-cholesterol diet on markers of uterine contractility during parturition in the rat

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, nZ10) or HFHC (nZ10) 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 2a (PGF 2a ) 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 2a versus CON (P!0.01, P!0.01, PZ0.05 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 (PZ0.059). 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.

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

“…Decreased Cx43 expression is observed in multiple tissues upon lipid overload, including in adipose tissues after a HFD challenge (Elmes et al, 2011; Keller et al, 2008; Noyan-Ashraf et al, 2013). Cx43 expression has an inverse correlation with glucose and insulin levels, and is implicated in aging and obesity in two mouse strains (Keller et al, 2008).…”

Androgens in pregnancy: roles in parturition

“…Connexins are gap junction trans-membrane proteins that assemble to form a gap junction; Con43 is the predominant connexin involved in the initiation of MSMC contractions at term (Chow and Lye, 1994). A study in pregnant rats on a high Ch diet showed that high Ch is associated with a decrease in Con43 protein in the myometrium, suggesting possible implications for uterine contractility (Elmes et al , 2011). A study in isolated rat cardiac myocytes demonstrated that gap junctional intracellular communication (GJIC) disturbance, by either silencing the gene for Con43 or by addition of specific drugs, such as heptanol, induced a significant reduction in Ca 2+ transients, suggesting that Con43 may be involved in the regulation of basal Ca 2+ signalling in these cells (Li et al , 2012).…”

Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

“…A high fat diet induced low CX43 protein levels, which was restorable by pharmacological intervention in cardiac tissues of 32 wk old mice (Noyan-Ashraf et al , 2013). Also, decreased CX43 levels in autopsied uterine tissue were demonstrated in rats fed a high fat and high cholesterol diet (Elmes et al , 2011). Our data thus exhibit that CX43 protein levels are decreased during progressive obesity consistent with data in non-ovarian tissues.…”