A pilot study of the association between maternal mid-pregnancy cholesterol and oxysterol concentrations and labor duration.

BACKGROUND: Previous animal model studies have highlighted a role for cholesterol and its oxidized derivatives (oxysterols) in uterine contractile activity, however, a lipotoxic state associated with hypercholesterolemia may contribute to labor dystocia. Therefore, we investigated if maternal mid-pregnancy cholesterol and oxysterol concentrations were associated with labor duration in a human pregnancy cohort. METHODS: We conducted a secondary analysis of serum samples and birth outcome data from healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22-28 weeks of gestation. Serum was analyzed for total-C, HDL-C, and LDL-C by direct automated enzymatic assay and oxysterol profile including 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24-hydroxycholesterol (24OHC), 25-hydroxycholesterol (25OHC), 27-hydroxycholesterol (27OHC), and 7-ketocholesterol (7KC) by liquid chromatography-selected ion monitoring-stable isotope dilution-atmospheric pressure chemical ionization-mass spectroscopy. Associations between maternal second trimester lipids and labor duration (minutes) were assessed using multivariable linear regression adjusting for maternal nulliparity and age. RESULTS: An increase in labor duration was observed for every 1-unit increment in serum 24OHC (0.96 min [0.36,1.56], p < 0.01), 25OHC (7.02 min [1.92,12.24], p = 0.01), 27OHC (0.54 min [0.06, 1.08], p < 0.05), 7KC (8.04 min [2.7,13.5], p < 0.01), and total oxysterols (0.42 min [0.18,0.06], p < 0.01]. No significant associations between labor duration and serum total-C, LDL-C, or HDL-C were observed. CONCLUSIONS: In this cohort, mid-pregnancy concentrations of maternal oxysterols (24OHC, 25OHC, 27OHC, and 7KC) were positively associated with labor duration. Given the small population and use of self-reported labor duration, subsequent studies are required for confirmation.

Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors.

Transcription factor genes governing pigment cell development that are associated with spotting mutations in mice include members of several structural transcription factor classes but not members of the basic helix-loop-helix (bHLH) class, important for neurogenesis and myogenesis. To determine the effects of bHLH factor expression on pigment cell development, the neurogenic bHLH factor Mash1 was expressed early in pigment cell development in transgenic mice from the dopachrome tautomerase (Dct) promoter. Dct:Mash1 transgenic founders exhibit variable microphthalmia and patchy coat color hypopigmentation. Transgenic F1 mice exhibit microphthalmia with complete coat color dilution. Marker analysis demonstrates that Mash1 expression in the retinal pigmented epithelium (RPE) initiates neurogenesis in this cell layer, whereas expression in remaining neural crest-derived melanocytes alters their differentiation, in part by profoundly downregulating expression of the p (pink-eyed dilution) gene, while maintaining their cell fate. The effects of transcriptional perturbation of pigment cell precursors by Mash1 further highlight differences between pigment cells of distinct developmental origins, and suggest a mechanism for the alteration of melanogenesis to result in marked coat color dilution.