Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

Alqahtani, Saeed; Heath, Andrew C.; Quenby, Siobhán; Dawood, Feroza; Floyd, Rachel V.; Burdyga, Theodor; Wray, Susan

doi:10.1007/s00125-011-2371-6

Cited by 39 publications

(33 citation statements)

References 45 publications

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“…This adds to previous in vitro studies showing contractility reflecting different clinical conditions, such as diabetes, obesity and postterm pregnancies [10], [26], [27]. Myometrium from twin pregnancies has contractions that are shorter but more frequent than myometrium from singleton pregnancies.…”

Section: Discussionsupporting

confidence: 58%

“…Previous work from our group has shown that in vitro myometrial contractility can reflect in vivo clinical activity and labour outcome [10], [11]. The question therefore arises whether in vitro activity of myometrium from twins is different to that of singletons, making it a useful model for mechanistic studies focussed on risk of preterm labour.…”

Section: Introductionmentioning

confidence: 99%

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A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

et al. 2013

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ObjectiveOver half of twin pregnancies in US and UK deliver prematurely but the reasons for this are unclear. The contractility of myometrium from twin pregnancies has not been directly investigated. The objective of this research was to determine if there are differences in the contractile activity and response to oxytocin, between myometrium from singleton and twin pregnancies, across a range of gestational ages. Furthermore, we wished to determine if contractile activity correlates with increasing level of stretch, using neonatal birth weights as a marker of uterine stretch.MethodsThis was an in vitro, laboratory based study of myometrial contractility in women pregnant with one or two babies, using biopsies obtained from non-labouring women undergoing Caesarean section. Spontaneous, oxytocin-stimulated and depolarization induced contractile activity was compared.ResultsDirect measurements of myometrial contractility under controlled conditions show that the frequency of contractions and responses to oxytocin are significantly increased in twins compared to singletons. The duration of contraction however was significantly reduced. We find that contractile activity correlates with increasing levels of stretch, using neonatal birth weights as a surrogate for uterine stretch, with response to oxytocin being significantly positively correlated with birth weight.ConclusionsWe have found significant differences in contractile properties between myometrium from singleton and twin pregnancies and that increasing uterine stretch can alter the contractile properties of myometrium. We discuss the implication of these findings to preterm delivery and future studies.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

et al. 2013

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“…However, published research from other investigators provides further explanation as to how these clinical factors may modify the biologic effect of oxytocin in various ways. Compared to non-diabetic women, diabetic women have reduced myometrial muscle mass and decreased calcium channel receptors and calcium signaling in their myometrial tissues [21]. While both the diagnosis of preeclampsia and magnesium use were more common among women who received oxytocin doses >20 mu/min in univariable analysis, only magnesium use was demonstrated to be independently associated with high oxytocin dose after controlling for confounders.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with higher oxytocin requirements in labor

Frey

Tuuli

England

et al. 2014

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. Methods A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004-2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Results Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birth weight >4000 gm, intrapartum fever, administration of magnesium, and induction of labor. Conclusions Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

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“…Consequently, insulin can lead to muscle hypertrophy. Interestingly, diabetes has been associated with impairment of uterine contractility [18]. It is very likely that uterine hypertrophy in the adult Bscl2 −/− mice is the consequence of elevated glucose levels and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…We have been studying the functions of seipin in reproductive systems using seipin-deficient Bscl2 −/− mice and identified roles of seipin in mammary gland development, vaginal opening, and spermatogenesis [11,12]. Since seipin deficiency is associated with muscle hypertrophy and diabetes [10,17], diabetes has been associated with impairment of uterine contractility [18], and uterine smooth muscle contractions are critical for parturition, it was hypothesized that seipin deficiency might affect the myometrium to influence parturition. This hypothesis was tested in seipin-deficient Bscl2 −/− adult female mice.…”

Section: Introductionmentioning

confidence: 99%

Seipin deficiency leads to defective parturition in mice†

Zowalaty

2017

Biology of Reproduction

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Seipin is an integral endoplasmic reticulum membrane protein encoded by Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2/Bscl2) gene. Seipin deficiency results in lipodystrophy, diabetes, muscle hypertrophy, and male infertility in both human and mouse. Seipin function in female reproduction is unknown. Bscl2 −/− dams had normal embryo implantation and body weight gain during pregnancy but reduced delivery rates from 2nd to 4th pregnancies and reduced numbers of pups delivered from 1st to 4th pregnancies. Characterization of first pregnancy revealed increased gestation period and parturition problems, including uterine prolapse, difficulty in delivery, undelivered fetuses, and undelivered tissues in Bscl2 −/− females. Bscl2 −/− uterine weight was comparable to control at 3 weeks old but significantly increased with myometrial hypertrophy at 10 months old. In situ hybridization revealed relatively low level of Bscl2 mRNA expression in myometrium throughout pregnancy and postpartum but high level of expression in uterine luminal epithelium, suggesting that systemic effect (e.g. elevated glucose and insulin levels) rather than local seipindeficiency in myometrium might be a main contributing factor to myometrial hypertrophy. On near-term gestation day 18.5 (D18.5), Bscl2 −/− females had normal levels of serum progesterone and 17β-estradiol, indicating functional ovary and placenta. Proliferating Cell Nuclear Antigen (PCNA) staining showed minimal myometrial cell proliferation in both D18.5 Bscl2 +/+ and Bscl2uteri. There was strong LC3 immunostaining in Bscl2 +/+ and Bscl2 −/− peripartum myometrium and increased LC3 staining in Bscl2 −/− peripartum uterine luminal epithelium, suggesting a potential role of seipin in regulating autophagy in uterine luminal epithelium but not myometrium. This study demonstrates an association of seipin with myometrium and parturition. Summary SentenceOur findings that seipin deficiency in mice leads to myometrial hypertrophy and parturition problems reveal a novel in vivo function of seipin in parturition.

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Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

Cited by 39 publications

References 45 publications

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

A Comparison of the Contractile Properties of Myometrium from Singleton and Twin Pregnancies

Factors associated with higher oxytocin requirements in labor

Seipin deficiency leads to defective parturition in mice†

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