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Over 35% of reproductive-age women in the USA have obesity, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity and found that these mice had a higher rate of dystocia than control chow-fed mice. Moreover, compared to control chow-fed mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that diet-induced obesity is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. Diet-induced obesity uteri also had an increase in the abundance of long chain-specific beta-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aimed to investigate the relationship between maternal serum lipid parameters and oxytocin requirements among women with term vaginal deliveries., Study Design: In this secondary analysis of a prospective cohort study, women who presented for delivery at ≥37 weeks' gestation and received oxytocin during their labor were included. Maternal serum was collected intrapartum. The cohort was stratified into two groups based on maximum oxytocin infusion dose during labor. Primary outcomes were maternal total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. Generalized linear regression models were used to assess the association between lipid parameters and maximum oxytocin dose requirements while controlling for potential confounders. For secondary analyses, the cohort was stratified by HDL-C into two groups. Multivariable logistic regression was used to evaluate the relationship between low maternal HDL-C and additional intrapartum oxytocin parameters., Results: There were no differences in maternal total cholesterol, LDL-C, or triglyceride values between high and low maximum oxytocin groups. Median serum HDL-C was significantly lower among women in the high oxytocin group compared with those in the low oxytocin group (56 vs. 62 mg/dL, p  < 0.01). For every 0.26 mg/dL lower HDL-C, women had 1 mU/min higher maximum oxytocin infusion dose during labor. Women with low serum HDL-C were also more likely to require maximum oxytocin doses above the 75th percentile (adjusted odds ratio [aOR]: 1.99, 95% confidence interval [CI]: 1.06-3.75) and above the 90th percentile (aOR: 2.47, 95% CI: 1.10-5.54). Among women undergoing induction of labor, low serum HDL-C was also associated with longer duration of oxytocin infusion (aOR: 2.07, 95% CI: 1.02-4.20)., Conclusion: Low maternal HDL-C levels at term are associated with higher maximum oxytocin infusion doses among women undergoing labor induction or augmentation. Given the growing prevalence of metabolic syndrome in the United States and persistently high rates of cesarean delivery, HDL-C or its components may present a new target for predicting and improving labor outcomes., Key Points: · Serum HDL-C at term is inversely correlated with oxytocin infusion doses at term.. · Low maternal serum HDL-C is associated with higher oxytocin requirements during labor induction or augmentation.. · No association between maternal serum total cholesterol, LDL-C, or triglyceride levels and oxytocin requirements in labor.., Competing Interests: None declared., (Thieme. All rights reserved.)

One of the common mechanisms responsible for obstetric complications, affecting millions of women every year, is abnormal uterine contractility. Despite the critical importance of this process for women's health, the mechanisms of uterine contraction regulation remain poorly understood. The initiation of uterine smooth muscle (myometrial) contraction is an inflammatory process, accompanied by upregulation of proinflammatory genes and cytokine release. In this study, we show that sphingolipid metabolism is activated during human labor and that sphingosine 1-phosphate (S1P), the main bioactive sphingolipid, may modify the myometrial proinflammatory phenotype. Our data in both primary and immortalized human myometrial cells show that exogenous S1P induces a proinflammatory gene signature and upregulates the expression of known inflammatory markers of parturition, such as IL8 and COX2. Using expression of IL8 as a readout for S1P activity in myometrial cells, we established that these S1P effects are mediated through the activation of S1P receptor 3 (S1PR3) and downstream activation of ERK1/2 pathways. Inhibition of S1PR3 in human myometrial cells attenuates upregulation of IL8, COX2, and JUNB both at the mRNA and protein levels. Furthermore, activation of S1PR3 with a receptor-specific agonist recapitulated the effects seen after treatment with exogenous S1P. Collectively, these results suggest a signaling pathway activated by S1P in human myometrium during parturition and propose new targets for development of novel therapeutics to alter uterine contractility during management of preterm labor or labor dystocia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)