Myometrium

Preterm birth (PTB) is a major public health problem, with a global prevalence of 9.6% and over a million annual neonatal deaths. In a mouse model of preterm labor (PTL) induced by intravaginal administration of a subclinical dose of lipopolysaccharide (LPS), we previously demonstrated that LPS ascends to the cervix, inducing complement activation, cervical remodeling and PTL. Here we show that complement activation also plays a role in myometrial contractions during PTL in this model. Increased levels of C5a were detected in the myometrium of LPS-treated mice but not in age-matched control or term myometrium. Human and mouse myometrium incubated with C5a showed increased frequency of contractions and expression of connexin 43, suggesting that C5a is an uterotonic molecule. Statins, which showed beneficial effects in preventing complement-mediated pregnancy complications, prevented cervical remodeling, myometrial contractions and PTL in the LPS model. The protective effects of stati...

Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture.FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2–4 fold lower (P < 0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P < 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space.Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA.Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.

Summary. The existing data on the hormonal factors involved in human parturition indicate that the steroid hormones, progesterone and the oestrogens, play only a facilitatory role in the initiation of labour. A definite role for fetal adrenal steroids in this process has yet to be established, and they too may serve only a facilitating function. The stimulation of the uterine muscle during labour results from an interaction of oxytocin and prostaglandin (PG) F2α. Recent evidence suggests that oxytocin is most important for the initial phase of labour, whereas increased synthesis of PGF2α is essential for the progression of labour. The role of PGE2 remains unclear, but this PG may play an important role in the ripening of the cervix which in turn is essential for successful parturition. The finding of maximal oxytocin receptor concentrations in the myometrium in labour adds strong support to the notion that oxytocin is the trigger for uterine contractions. The factors which control oxytocin receptor formation are therefore important; this may be one of the processes where the steroids play a crucial role. Oxytocin is also one of the stimuli that increase uterine PG synthesis; the coupling of oxytocin receptor occupancy and PG synthetase activity in uterine tissues may be another crucial factor in the mechanism of labour. The formation of gap junctions between the myometrial cells also seems essential for the synchronization and progression of myometrial activity. We propose, therefore, that the co-ordinating of oxytocin receptor formation, PG synthesis and gap junction formation is a key to the initiation and maintenance of human labour. The fetus may fulfil such a co-ordinating role through its influence on placental oestrogen production, through mechanical distention of the uterus, and through its secretion of neurohypophysial hormones and other stimulators of PG synthesis.

The presence of fatty tissue in the myometrium is anomalous; this alteration has been interpreted either as a lipomatous degeneration or as a metaplasia of smooth muscle cells or, still, as a real neoplasm, frequently associated with a leiomyoma, the so-called lipoleiomyoma. The observation of a case of lipoleiomyoma stimulated us to ascertain the real incidence of this lesion which is commonly considered to be rare. We examined 620 single or multiple uterine leiomyomas with extensive sampling of all the areas suspected to contain fatty tissue islands. Five times out of seven the presence of fat cells in a leiomyoma resulted to be a true lipoleiomyoma. It has thus been possible to ascertain the incidence of lipoleiomyoma versus uterine leiomyomatosis (0.8%). Futhermore we observed a prevalence in menopause, an association with multiple leiomyoma and a preferential onset in the subserosa. The pathogenesis of this lesion, which can be fully ascribed to a mixed, benign, heterologous, m...

This study was undertaken to identify the molecular basis of an arrest of descent.Human myometrium was obtained from women in term labor (TL; n = 29) and arrest of descent (AODes; n = 21). Gene expression was characterized using Illumina HumanHT-12 microarrays. A moderated Student t test and false discovery rate adjustment were applied for analysis. Confirmatory quantitative reverse transcription–polymerase chain reaction and immunoblot were performed in an independent sample set.Four hundred genes were differentially expressed between women with an AODes compared with those with TL. Gene Ontology analysis indicated enrichment of biological processes and molecular functions related to inflammation and muscle function. Impacted pathways included inflammation and the actin cytoskeleton. Overexpression of hypoxia inducible factor-1a, interleukin -6, and prostaglandin-endoperoxide synthase 2 in AODes was confirmed.We have identified a stereotypic pattern of gene expression in the myometrium of women with an arrest of descent. This represents the first study examining the molecular basis of an arrest of descent using a genome-wide approach.

To survey all gynaecologists in Canada to determine the number who perform or offer the laparoscopic myomectomy (LM) procedure, the barriers that deter gynaecologists from performing or offering LM, and to understand the perceptions and attitudes of Canadian gynaecologists with respect to LM. A survey was developed, pre-tested, and distributed to all 1279 obstetrician-gynaecologists on the SOGC mailing list in April 2007. A total of 529 obstetrician-gynaecologists participated in the survey a response rate of 41.4%. Of the 485 respondents who practised gynaecology, 119 (24.5%) performed LM, but only 15 (3.1%) stated that more than 50% of their myomectomies were performed laparoscopically. Two hundred twelve gynaecologists (44.3%) admitted to having referred a patient to another gynaecologist for LM. Laparoscopic surgeons felt the principal barrier to performing LM was lack of training in the procedure (70.7%). Gynaecologists felt the principal barrier to referring to another gynaecologist for LM was their uncertainty about who offered the procedure (33%). The majority of gynaecologists believed that LM has faster recovery time. The majority of respondents, however, were unsure which procedure is superior with respect to blood loss, adhesion formation, fertility rate post-procedure, uterine rupture rate in subsequent pregnancy, and cost-effectiveness. Despite existing evidence that indicates that LM is comparable to abdominal myomectomy with respect to complication rates and fertility, only one quarter of Canadian gynaecologists who responded to this survey performed the procedure. Barriers to performing LM included lack of training and barriers to referral included uncertainty about who offered the procedure.