Non-pregnant Uterus Research Articles

Three‐dimensional fiber architecture of the nonpregnant human uterus determined ex vivo using magnetic resonance diffusion tensor imaging

The global muscle and collagen fiber orientation in the human uterus has been analyzed hitherto by various standard microscopic techniques. However, no widely accepted model of the fiber architecture of the myometrium could be acquired. The purpose of the present study was to investigate the uterus by magnetic resonance (MR) diffusion tensor imaging (DTI) in a 3D macroscopic approach. Ex vivo MR DTI measurements were performed on five uteri from nonpregnant patients. The main diffusion directions reflecting the orientation of directional structures in the examined tissues were determined from diffusion-weighted spin-echo measurements. A fiber tracking algorithm was used to extrapolate the fiber architecture. The method was validated against histological slides and indirectly through the analysis of leiomyomas, which exhibit less anisotropy than normal myometrium. Significant anisotropy was found in most regions of all examined nonpregnant human uteri. But only two systems of fibers were found running circularly along the intramural part of the uterine tubes. They merged caudally and built a close fitting envelope of circular layers around the uterine cavity. On the cervix, circular fibers were observed in the outer part as well as mostly longitudinal fibers in the inner part. These results confirm the existence of directional structures in the complex fiber architecture of the human uterus. They also indicate that MR DTI is a beneficial and complementary tool to standard microscopic techniques to determine the intrinsic fiber architecture in human organs.

Histo-morphology of the Uterus and Early Placenta of the African Buffalo ( Syncerus caffer) and Comparative Placentome Morphology of the African Buffalo and Cattle ( Bos taurus)

Differences exist in reproductive physiology between African buffalo (Syncerus caffer), cattle (Bos taurus) and water buffalo (Bubalus bubalis). The aim of this study was to histo-morphologically compare the anatomy of non-pregnant and pregnant uteri of buffalo and cattle. Two non-pregnant uteri and placentae of six pregnant African buffalo were used. Early placentome formation (fetal crown rump length (CRL): 2-17.5 cm) in S. caffer and B. taurus was compared. The endometrium of buffalo uteri comprises round to ovoid, dome-shaped and gland-free caruncles. A predominantly simple columnar epithelium of non-ciliated cells covers caruncular tissue, while, additionally, ciliated cells occur in the epithelium of the intercaruncular areas and within the simple columnar or pseudostratified epithelium of the endometrial glands. During early gestation, multiple placentomes develop. Unlike the placentomes in cattle at similar CRL, buffalo placentomes do not develop a caruncular stalk. The sessile, dome-shaped buffalo placentome has simple, slightly conical villi branching less than in cattle, thus indicating different and less complex feto-maternal interdigitation than seen in the latter. A synepitheliochorial interhaemal barrier can be expected in the buffalo placenta, as the occurrence and ultrastructure of trophoblast giant cells resemble those described in cattle.

Physiology of the corpus luteum

My life with progesteroneAmerican Journal of Obstetrics & GynecologyVol. 193Issue 4PreviewThe twists and turns of fate have linked my name so many times with the other ovarian hormone that I still shudder when some senior citizen says, “You must have been awfully young when you worked with Doisy.” The confusion arises because there are 2 Allens whose names have become attached to the 2 ovarian hormones. Edgar Allen (1892-1943) and Edward Adelbert Doisy (1893-1986) announced their discovery of a hormone in the ovarian follicular fluid in 1923.1 George Washington Corner (1889-1981) and I announced the discovery of a second ovarian hormone in the corpus luteum in 1929. Full-Text PDF Comment by Lawrence D. Longo, MDAmerican Journal of Obstetrics & GynecologyVol. 193Issue 4PreviewGeorge Washington Corner (1889-1981) and Willard Myron Allen (1904-1993) (the latter a medical student at the time) first obtained a secretory endometrium in the rabbit uterus after injection of an extract of corpus luteum, which laid the groundwork for the isolation of progesterone. Illustrated above, several figures are from a nonpregnant rabbit uterus after an ophorectomy and various treatments: 1 and 5, Normal control from mature rabbit; 7, control from immature rabbit; 2, proliferative endometrium in response to 5 days treatment with corpus luteum extract; 3, same after a larger dose; 8, same in immature animal; 4, same after one-half minimal effective dose; 6, treatment with follicular fluid (presumably containing estrogen); 9, same in immature animal. Full-Text PDF

Endometriose und Adenomyose

Peristaltic activity of the non-pregnant uterus serves fundamental functions in the early process of reproduction. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have an increased potential of implantation and proliferation resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of about 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. The principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary thus resulting in hyperperistalsis. Minimal endometriosis of the fertile women, endometriosis and adenomyosis of the infertile women and adenomyosis of the parous peri- and postmenopausal women are considered as phenotypes of a pathophysiological continuum with uterine peristalsis playing a prominent role.

Unaltered innervation of the human cervix uteri in contrast to the corpus during pregnancy and labor as revealed by PGP 9.5 immunohistochemistry

Objective To examine the occurrence of the general neuronal marker protein gene product 9.5 (PGP 9.5) in the human corpus (isthmus region) and the cervix uteri during pregnancy and parturition Study design Biopsies were taken from the upper edge of the hysterotomy during caesarean section (CS) at term ( n = 5), in labor ( n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy ( n = 5). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostate sections were prepared for immunohistochemistry using polyclonal antibodies to PGP 9.5. Results Nerve fibers displaying PGP 9.5 immunoreactivity were observed in all sections from the three groups examined. They were identified in muscle tissue, in the stroma, and around blood vessel walls. A 30-fold decline of immunoreactive nerve fibers was observed in the isthmus part of the corpus uteri at term compared to the non-pregnant. There were no significant differences between the immunoreactivity in the cervix uteri of the three groups Conclusions The innervation of the cervix uteri is dense and unaltered throughout pregnancy and labor. In contrast, the corpus is almost denervated. Further studies are needed to clarify the reason and the impact of these findings.

Contractile reactivity of human myometrium in isolated non-pregnant uteri

Perfusion of the isolated uterus has been shown to be a feasible experimental system for studies of the human endometrium and myometrium. Utilizing our established experimental perfusion model we perfused 20 uteri for 27 h and investigated the contractile reactivity of the myometrium in response to 17beta-estradiol (E2) and oxytocin (OT). Uteri of group A (n = 4) were stimulated with OT; group B (n = 4) was treated continuously with E2; group C (n = 4) received both E2 and OT for 27 h; group D (n = 4) was perfused for 27 h with E2 with the addition of OT for the last 3 h of the experiment; group E (n = 4) as control group remained without any treatment. The pressure and duration of uterine contractions were recorded during the entire perfusion period using intramural and endoluminal pressure catheters. Compared to the other treatment groups and controls, the most effective myometrial activity was achieved in group D during the OT stimulation period. No relevant myometrial activity was detected in the control group. Continuous E2 treatment, with the addition of OT for the last 3 h of the 27 h perfusion period, led to the most pronounced uterotonic effects in the presented experimental condition.

Udder development, lactation and ascites in a ewe with an ovarian granulosa cell tumour

A 20-month-old sexually intact female mixed breed sheep was examined for lameness, unexpected udder development, lactation and anorexia. Tachycardia, tachypnoea, severe abdominal distension and vaginal prolapse were evident upon physical examination. A right hindlimb lameness was present at the walk. The udder was well-developed and milk, normal in appearance, was easily expressed from each teat. Ultrasonographic evaluation revealed a non-pregnant uterus, severe ascites and a large (12 cm diameter) abdominal mass. Although surgical treatment was discussed, the owners elected to euthanase the ewe. Necropsy examination confirmed the presence of severe ascites due to a ruptured ovarian tumour. The tumour was characterised as a granulosa cell tumour histologically. Unexpected udder development and lactation presumably occurred secondary to oestrogen and progesterone production by the tumour. To the authors' knowledge, this is the first report of udder development, lactation and ascites in a ewe secondary to an ovarian granulosa cell tumour.

Expression and Localization of Alpha-Smooth Muscle and Gamma-Actins in the Pregnant Rat Myometrium1

The myometrium undergoes dramatic changes as pregnancy progresses through phases of proliferation, hypertrophy, contractile state and labor. In this study, we showed that the composition of the muscle actin isoforms, a major component of the myometrial contractile apparatus and cytoskeleton, was modified during pregnancy. The expression of smooth muscle alpha-actin (Acta2, which we abbreviate as alpha-SM-actin) and gamma-actin mRNAs and proteins was examined by real-time polymerase chain reaction and Western immunoblot, and was localized with immunohistochemistry, in the nonpregnant, pregnant, and postpartum rat uterus. Both alpha-SM-actin (vascular specific actin isoform) and gamma-actin (predominant in visceral smooth muscle) were detected in the rat myometrium. Myometrial expression of alpha-SM-actin mRNA and protein was high throughout pregnancy. The transcript and protein levels of gamma-actin were increased significantly in the second part of gestation (31.8-fold increase for mRNA and 16.7-fold increase for protein relative to nonpregnant). The localization of gamma-actin was markedly altered during pregnancy. In early gestation, myometria from empty and gravid uterine horns of the unilaterally pregnant rats showed abundant gamma-actin immunostaining in the longitudinal layer but weak staining in the circular layer. Gamma-actin immunostaining increased in only the circular layer of the gravid horn after midgestation and remained low in the empty one. Gamma-actin protein translocated to the membranous region of uterine myocytes at late gestation. The temporal alteration in gamma-actin expression and localization at late gestation suggested that this change in myometrial composition of contractile proteins is important to adequately prepare the myometrium for the development of optimal contractions during labor.

Snake venom derived fibrin adhesive in dog uterine healing: biomechanical study

Healing is a complex process with many interfering factors. The objective of this work was to evaluate regeneration strength of non-pregnant adult dog uterus when snake venom derived fibrin adhesive is used to reinforce hysterorrhaphy. Maximum limit and rigidity were analyzed. Twenty uterine horns from 10 dogs were hysterotomized and distributed into 2 equal groups. Hysterorrhaphy was performed using the Shimieden-Cushing double layer suture. In one group, animals received snake venom derived fibrin adhesive as reinforcement. Although neither variable was significantly different, our results showed higher rigidity values in the adhesive group. This can be attributed to the adhesive’s effect on organ elasticity or to more granulation tissue formed in the uterine scar.

Selective distribution and pregnancy-specific expression of DC-SIGN at the maternal–fetal interface in the rhesus macaque: DC-SIGN is a putative marker of the recognition of pregnancy

We performed immunohistochemical analysis of DC-SIGN expression at the maternal-fetal interface at different stages of pregnancy in the rhesus monkey. Natural killer cells, monocytes and macrophages were observed in the nonpregnant endometrium, particularly in the luteal phase, and were increased in pregnant endometrium. No DC-SIGN+ cells were observed in the nonpregnant uterus. We observed decidual DC-SIGN+ cells within 1 week of implantation, and they increased in number during the first 5 weeks of gestation. DC-SIGN+ cells showed a clear differential distribution in the decidua in the first 2 weeks of pregnancy, being found only adjacent to the implantation site, in marked contrast to the widespread distribution of CD68+ macrophages and CD56+ NK cells throughout the endometrium. DC-SIGN+ cells also showed a more dendritic morphology than the general CD68+ cell population, and analysis of serial sections indicated an overlapping but not identical localization of these markers. Mature dendritic cells could not be detected as judged by total absence of immunostaining for CD83, CD86, DEC-205, or CD1a. DC-SIGN+ cells were defined as MHC class II+ and CD14+ by flow cytometry. We conclude that DC-SIGN expression is an early response by the primate maternal immune system to the implanting embryo. The selectively distributed population of DC-SIGN+ decidual leukocytes may represent a morphologically and phenotypically distinct subpopulation of decidual macrophages of early pregnancy that could contribute to the establishment of maternal-fetal immune tolerance.

Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists have different activity profiles.

1. The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F(2alpha) (PGF(2alpha))-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC(50)=7.92+/-0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. 2. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF(2alpha) (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 muM bimatoprost on the mouse uterus. Analyses of the agonist-agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. 3. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF(2alpha). Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. 4. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.

Localization of Interleukin-6 Receptor mRNA in the Pregnant and Non-pregnant Mouse Uterus

To understand roles of interleukin 6 (IL-6) family cytokines for pregnancy in mice, localization of IL-6 receptor (IL-6R) mRNA was investigated in non- and early pregnant uteri by in situ hybridization. IL-6R mRNA was expressed in all non-pregnant uteri and in pregnant uteri from the third day (Day 3) to the sixth day of pregnancy (Day 6; the day of plug = Day 1). IL-6R mRNA signals were detected in non-pregnant mice in the luminal and glandular epithelium. Signal strength varied according to the sexual cycle. There was no correlation between the signal strength of the IL-6R mRNA and the serum concentrations of progesterone and 17beta-estradiol, which show a monophasic rise in the non-pregnant sexual cycle. In pregnant mice, slight signals were detectable in the luminal and glandular epithelium on Day 3. IL-6R mRNA messages increased with progression towards Day 4, however, localization changed drastically on Day 5. Stromal cells abruptly expressed their mRNA on Day 5, and these cells strongly expressed it on Day 6. The function of IL-6R in the luminal and glandular epithelium might be different from that in the stroma during the implantation period. In addition, few signals were identified in the stromal cells adjacent to the luminal epithelium on Day 6. This suggests that there are two types of stromal cells on Day 6 in mice.

Uterine region-dependent differences in responsiveness to prostaglandins in the non-pregnant porcine myometrium

To clarify the uterine region-dependent distribution of prostanoid receptors, we compared the mechanical responses to selective prostanoid receptor agonists (FP, EP 3, DP, EP 2) and naturally occurring prostaglandins (PGF 2α, PGE 2, PGD 2) in longitudinal and circular muscles isolated from three different regions (cornu, corpus and cervix) of the non-pregnant porcine uterus. Expression levels of FP receptor and cyclooxygenase (COX-1 and COX-2) in the respective regions were also examined using RT-PCR and Western blotting. The contractile responses to fluprostenol (an FP agonist) and PGF 2α in both longitudinal and circular muscles were strongest in the cornu but weak in the corpus and cervix. Expression levels of mRNA and protein of FP receptor were highest in the cornu, consistent with the contractile responses. ONO-AE-248 (an EP 3 agonist) caused contraction of both muscle layers, but region-related difference in responsiveness was observed only in the longitudinal muscle. ONO-AE1-259 (an EP 2 agonist) inhibited spontaneous contraction of the myometrium, and inhibition was conspicuously stronger in the cervix. PGE 2 caused contraction (<100 nM, cornu > corpus = cervix) and inhibition (>300 nM, cornu = corpus ≦ cervix) of contractility depending on the concentration in both muscle layers. BW245C (a DP agonist) inhibited the spontaneous contraction, and region-dependent different responsiveness was marked in the longitudinal muscle (cervix = corpus > cornu). COX-1 but not COX-2 was detected in the non-pregnant porcine uterus. Expression level of COX-1 was different in the longitudinal muscle (cornu > corpus = cervix) but the same in the circular muscle. SC-560 inhibited the spontaneous contraction of longitudinal muscles in all regions. The results of the present study indicate that there are region-related heterogeneous distributions of contractile (FP and EP 3, cornu > cervix) and relaxant (EP 2 and DP, cervix > cornu) prostanoid receptors and COX-1 in the porcine uterus. The results also suggest involvement of endogenous PGs in the regulation of spontaneous uterine contractility. Region-related differences in COX-1 and prostanoid receptors might be necessary to produce a gradient of uterine motility decreasing from the cornu to the cervix that manages movement of luminal contents.

The effect of vascular origin, oxygen, and tumour necrosis factor alpha on trophoblast invasion of maternal arteriesin vitro

Extravillous trophoblasts (EVTs) invade and remodel uterine spiral arteries. Regulatory factors may include inherent vessel susceptibility, local oxygen levels and tumour necrosis factor alpha (TNFalpha). We have used an in vitro model to investigate interstitial and endovascular invasion of myometrial spiral arteries from pregnant and non-pregnant uteri and also omental arteries. To model endovascular invasion, fluorescent-labelled EVTs were perfused into the lumen of these dissected vessels. For interstitial invasion, labelled EVTs were layered on top. Cultures were either maintained in 17% or 3% oxygen, or cultured with TNFalpha. The invasion of arteries from pregnant women occurred via both routes at 17% oxygen, with endovascular invasion more efficient than interstitial. In omental arteries and spiral arteries from non-pregnant women, endovascular invasion was limited. Endovascular and interstitial invasion were lower in all arteries at 3% oxygen. Typically, endovascular events were clustered, with an associated disruption in the adjacent endothelium and smooth muscle. A role for TNFalpha in limiting invasion was also supported. In conclusion, priming of uterine arteries may be necessary prior to EVT invasion. Oxygen is a sensitive regulator within this physiological model and increased invasion at higher pO2 may explain the homing of EVT to maternal arteries rather than veins. Adequate vascular transformation may therefore rely on a balance between vascular receptivity, oxygen partial pressure, and exposure to inflammatory mediators.

The Patterns of Uterine Contractility in Normal Menstruating Women: From Physiology to Pathology

The nonpregnant uterus shows uterine activity throughout the menstrual cycle. This uterine activity was detected both by single strep tissue and by using intrauterine pressure recordings in vitro and in vivo. Today, ultrasound has made it possible to study this activity with a noninvasive approach and to assess uterine contractions (UCs) in real-time movements of the uterus. Throughout the menstrual cycle, wavelike activity patterns of the reproductive organ were established. These patterns are under control of steroid hormones. Adequate UCs may provide for gamete/embryo transportation throughout the uterotubal cavities and successful embryo implantation in spontaneous and/or assisted reproduction. Inadequate UCs may produce ectopic pregnancy, miscarriages, retrograde bleeding with dysmenorrhea, and endometriosis.

Uterine Peristaltic Activity and the Development of Endometriosis

Peristaltic activity of the nonpregnant uterus serves fundamental functions in the early process of reproduction, such as directed transport of spermatozoa into the tube ipsilateral to the dominant follicle, high fundal implantation of the embryo, and, possibly, retrograde menstruation. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis, fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have, because of their equipment with estrogen and progesterone receptors and because of their ability to produce estrogen, an increased potential of implantation and proliferation, resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of approximately 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. Our own date and that from the literature strongly suggest that the principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary, thus resulting in hyperperistalsis.

Variation in Macrophage-Migration-Inhibitory-Factor Immunoreactivity During Porcine Gestation1

The localization and activity of macrophage migration inhibitory factor (MIF) was investigated in the interhemal region of the noninvasive, diffuse, folded epitheliochorial placenta and in the nonpregnant uterus of the pig. MIF, a proinflammatory cytokine with many actions on macrophages and monocytes, may play an important role in materno-fetal immuno-tolerance during placental establishment, modulation, and growth. Immunohistochemical staining with anti-human MIF polyclonal antibodies was carried out on placental sections from 11 stages of gestation (16-95 days postcoitus) and on nonpregnant uterus at 13 days postestrus. Western blot analysis confirmed the specificity of the anti-human MIF polyclonal antibodies on pig tissues. MIF staining was intense in both the trophoblast and maternal epithelium in the early stages; in the later stages, it decreased dramatically in the maternal epithelium but remained high in the trophoblast. The uterine glands showed immunoreactivity at all stages, and the maternal and fetal epithelial linings of the areolar cavity showed high reactivity at Day 25. The vasculature also showed staining for MIF, and an intense to moderate staining was shown in the nonpregnant uterus, mostly in the surface and glandular epithelium. The high activity of MIF in the maternal and fetal tissues throughout placentation and its expression in the nonpregnant uterus indicate a regulatory role for MIF during embryo receptivity and epitheliochorial placentation.

Effects of implantation and early pregnancy on the expression of cytokines and vascular surface molecules in the sheep endometrium

Successful implantation is a highly coordinated process involving changes in cytokines, adhesion molecules, hormones, enzymes and growth factors. This study examines the expression of key cytokines and vascular surface molecules in the pregnant uterus of sheep around the time of implantation. Uterine tissues and uterine washings were collected from non-pregnant and pregnant sheep at 17–19 days post-coitus (dpc), 26–27 and 34–36 dpc. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of caruncular/placentomal tissues revealed that cytokines IL-2, IL-4 and IL-8, which were not detected in non-pregnant uterus, were induced more strongly at 26–27 dpc than at other stages of pregnancy tested. Cytokines LIF, IL-6, IL-10, TNF-α were also most highly expressed at 26–27 dpc, expression of them being lower at other time-points during early pregnancy and non-pregnancy. The cytokines IL-1β, IFN-γ and TGF-β were expressed in all non-pregnant and pregnant tissues examined. Enzyme-linked immunosorbent assay (ELISA) performed on uterine washings clearly detected the presence of IL-1α protein at 26–27 and 34–36 dpc. Immunohistochemistry revealed that expression of vascular adhesion molecule VCAM-1 in endometrial endothelium was strongly induced at 26–27 dpc in the pregnant endometrium. Expression of CD5 on vascular endothelium was not induced in placentomal tissues until 26–27 dpc and was further increased by 34–36 dpc. These results demonstrate a dynamic change in a wide range of cytokines during early stages of pregnancy, with a critical period around 26–27 dpc. In addition, at 26–27 dpc, expression of the surface/adhesion molecules, CD5 and VCAM-1, is induced on vascular endothelium of the sheep endometrium, possibly as a direct consequence of the changed cytokine environment, and may be involved in directing the changes in leucocyte migration observed during pregnancy.

Analysis of spatial and temporal expression patterns of bone morphogenetic protein family members in the rat uterus over the estrous cycle.

Recent studies have demonstrated that bone morphogenetic proteins (BMPs) play fundamental roles in female fertility. This is particularly evident in terms of the ovary. One major question that is just beginning to be addressed is the role of BMPs in the non-pregnant uterus. To help fill this gap, we used in situ hybridization to investigate the expression of BMP family members in the rat uterus over the estrous cycle. We found that the endometrial/uterine cycle is accompanied by the expression of several components of the BMP pathway - including ligands, receptors and antagonists. The mRNAs encoding BMP receptors are expressed in the epithelial (BMP-RIA, -RIB and -RII), periluminal stroma (BMP-RIA and -RII) and smooth muscle cells (BMP-RIA and -RII). The expression of all three receptors showed clear cyclic variations. The mRNAs encoding BMP ligands were highly expressed in the periluminal stroma (BMP-2 and -7) and glandular epithelium (BMP-7). The expression of BMP-2, but not BMP-7, was cyclical. Notably, the periluminal stroma expressed noggin mRNA. In the blood vascular system, BMP-4, -6 and -RII mRNAs were expressed in myometrial endothelial cells. Interestingly, follistatin, noggin, and BMP-4, -6 and -7 mRNAs were expressed in eosinophilic leukocytes, suggesting unexpected roles for eosinophil-derived BMPs in uterine function. We conclude that BMP ligands, receptors and antagonists are expressed in spatially and temporally restricted patterns that are consistent with a physiological role for these regulatory molecules in promoting uterine cellular processes including cell proliferation, differentiation and apoptosis during the cycle.

The differential coupling of oxytocin receptors to uterine contractions in murine estrous cycle

Oxytocin (OT)-induced uterine contractility in different ovulatory phases has not been characterized in mouse. While the uterus was refractory to OT at diestrous phase, numerous contractions were observed at estrous phase. The magnitude of uterine contractile response to OT at estrous phase was larger than that at diestrous phase. There was also significant difference in the pD 2 values for OT between the samples from the two phases. However, the level of OT receptor (OTR) transcripts and proteins was equivalent at the two phases. These results suggest that OT-induced uterine contraction is not only regulated by the quantity of OTR in the non-pregnant mouse uterus.