Introduction:
Contractions of the myometrium, the muscle layer of the uterus, serve several physiological functions including menstruation and labour, with aberrant contractions associated with benign gynaecological disorders and obstetric complications such as adenomyosis and dystocia. The myometrium consists of three layers: the sub-endometrial inner (IM), sub-serosal outer (OM), and middle myometrium. Despite animal studies suggesting distinct contractile properties and physiological functions of the IM and OM, equivalent functional characterisation in humans is lacking.
Aim:
To characterise regional differences in the effect of oxytocin on human myometrium.
Methods:
Myometrial biopsies were collected from term-pregnant women undergoing elective caesarean section (n=17) and nonpregnant women (n=4) undergoing hysterectomy for benign gynaecological conditions at Liverpool Women’s Hospital with informed, written consent and REC approval (REC 10/H1002/49).
Paired strips (5x2x1mm) from the IM and OM were mounted in organ baths to record isometric tension. The effect of oxytocin (10-10-10-6M) on contraction amplitude (mN), mean integral of force (MIF, a.u), frequency (contractions/hour), and duration (min) were assessed relative to spontaneous contractions (taken as 100%). Concentration-response curves determined maximum effect (Emax). OM and IM responses were compared via paired Student’s t-test or Wilcoxon signed rank test, P<0.05 was significant.
Results:
Mean amplitude of pregnant IM spontaneous contraction was greater (9.27mN, SE 1.61) than the OM (6.24mN, SE 0.91) but not significant (P=.06, n=17). Similarly, nonpregnant IM mean contraction amplitude was greater (6.12mN, SE 2.18) than the OM (3.94mN, SE 0.807) (P=.31, n=4). No significant regional differences in duration, frequency, or MIF of spontaneous contractions were observed in the pregnant or nonpregnant myometrium.
Oxytocin increased mean contraction amplitude and MIF in both regions of the pregnant myometrium in a concentration-dependent manner (n=10). Amplitude Emax in the OM was 256% of control (SE 39.6) compared to 163% (SE 15.4) in the IM, but not significantly greater (P=.06). Overall MIF Emax in the OM and IM was equal; OM, 322% of control (SE 51.0) and IM, 328% of control (SE 45.2) (P=.1). A dose-dependent reduction in contraction frequency and prolongation of duration was observed in both layers, with no regional difference noted.
Similarly, a dose-dependent stimulatory effect of oxytocin on contraction amplitude and MIF was demonstrated in both regions of the nonpregnant myometrium (n=4). Contrasting with the pregnant myometrium, a trend toward increased response in the IM compared to the OM was observed. Dose-response curves were not fit due to sample size.
Comparing oxytocin’s effect in the pregnant and nonpregnant myometrium, oxytocin induced a significantly smaller uterotonic effect in the nonpregnant OM compared to the pregnant OM; 114% of control (SE 7.20) vs. 233% (SE 40.1) (P=.04). The same trend was observed in the IM, although not significant.
Conclusions:
Regional specific differences in spontaneous myometrial contractile activity highlight potential functional differences between the IM and OM, possibly supporting distinct physiological roles. An increased response to oxytocin in the pregnant myometrium and specifically in the OM, supports the proposed role of the OM in facilitating the powerful contractions in labour. The opposite layer-specific sensitivity to oxytocin in the nonpregnant myometrium may indicate processes relevant to nonpregnant uterine function, which warrant further investigation.