Structural response of microcirculatory networks to changes in demand: information transfer by shear stress

Matching blood flow to metabolic demand in terminal vascular beds involves coordinated changes in diameters of vessels along flow pathways, requiring upstream and downstream transfer of information on local conditions. Here, the role of information transfer mechanisms in structural adaptation of microvascular networks after a small change in capillary oxygen demand was studied using a theoretical model. The model includes diameter adaptation and information transfer via vascular reactions to wall shear stress, transmural pressure, and oxygen levels. Information transfer is additionally effected by conduction along vessel walls and by convection of metabolites. The model permits selective blocking of information transfer mechanisms. Six networks, based on in vivo data, were considered. With information transfer, increases in network conductance and capillary oxygen supply were amplified by factors of 4.9 +/- 0.2 and 9.4 +/- 1.1 (means +/- SE), relative to increases when information transfer was blocked. Information transfer by flow coupling alone, in which increased shear stress triggers vascular enlargement, gave amplifications of 4.0 +/- 0.3 and 4.9 +/- 0.5. Other information transfer mechanisms acting alone gave amplifications below 1.6. Thus shear-stress-mediated flow coupling is the main mechanism for the structural adjustment of feeding and draining vessel diameters to small changes in capillary oxygen demand.     

Effects of nicotine on oviducal blood flow and embryo development in the rat

Nicotine (5.0 mg/kg) was injected (s.c.) twice daily on Day 1 or Days 1-4 or 1-5 of pregnancy. Cumulative doses of nicotine retarded embryo cell cleavage and substantially reduced embryo cell number (saline vs nicotine: 42.5 +/- 1.7 vs 22.1 +/- 1.9 nuclei/embryo, at 12:00 h on Day 5; P less than 0.05). However, treatment for even 1 day (Day 1) significantly reduced cell number (saline vs nicotine: 42.5 +/- 1.7 vs 30.5 +/- 0.9, at 12:00 h day on Day 5; P less than 0.01). Nicotine injection also resulted in a marked and prolonged reduction in oviduct blood flow (pretreatment vs 90 min after nicotine: 0.61 +/- 0.06 vs 0.37 +/- 0.10 ml/min . g-1; P less than 0.005). The results indicate that, in the rat, even a brief exposure to nicotine, the chief alkaloid of tobacco, reduces oviducal blood flow and the rate of embryo cell proliferation. The embryo is therefore susceptible to the effects of nicotine before implantation.     

Reduction in endometrial neutrophils in proximity to implanting rat blastocysts.

An antiserum to rat neutrophils was raised and used to follow the distribution of endometrial neutrophils during the peri-implantation period. Uteri from four pregnant and four pseudopregnant rats killed at 14:00, 17:00, 20:30 and 23:00 h on day 5 of pregnancy and 09:00 h on day 6 were sectioned. Four sections from each of four implantation sites and four intersites from each rat were immunostained. There was wide variability among rats in the number of endometrial neutrophils, but a nested analysis of variance showed significantly fewer neutrophils at implantation sites than at intersites from 20:30 h onwards. This difference was primarily due to the presence of more neutrophils in intersite regions of the endometrium. The results from this study do not support a role for neutrophils in the implantation-associated increase in microvascular permeability or decidualization in rats.     

Distribution of laminin,vimentin and desmin in the rat uterus during initial stages of implantation

The aim of this study was to investigate the immunohistochemical distribution of laminin, vimentin and desmin during the implantation period in the rat since ECM remodelling and the expression of intermediate filaments (Ifs) is essential for successful decidualization and implantation. On day 4 of pregnancy, laminin was found in a few endometrial stromal cells (ESC), the basement membrane of the numerous endometrial blood vessels, in endometrial glands and as well as in the uterine epithelium. The localization of vimentin on day 4 of pregnancy was widespread in the ESC. However, desmin immunoreactivity was low in ESC on this day of pregnancy. On day 6 of pregnancy, laminin and vimentin were localized in the decidual area underlying luminal epithelium and around the implanting embryo. Additionally, desmin was found to be present densely in decidual cells of the anti-mesometrial region where implantation takes place. Finally, on day 8 of pregnancy, laminin was present in decidual and parietal endodermal cells, whereas vimentin was immunolocalized in primary and secondary decidual regions in the endometrium. In contrast, desmin was detected in some parts of the secondary decidual zone. In conclusion, these proteins could have crucial roles in decidualization and implantation.     

Role of endogenous nitric oxide generation in the regulation of vascular tone and reactivity in small vessels as investigated in transgenic mice using synchrotron radiation microangiography.

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role in regulation of vascular tone and reactivity. The purpose of this study is to clarify the basal tone and microvascular reactivity in eNOS-overexpressing transgenic (Tg) mice in vivo with a microangiography system using monochromatic synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic contrast media was injected, and microangiography was performed in hindlimbs of mice. Serial images of the small blood vessels (diameter <200 microm) were recorded by the SR microangiography system. At basal conditions, the diameter of tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 +/- 8 versus 132 +/- 8 microm; P < 0.01). l-NAME treatment decreased the vessel diameter and canceled the difference in vessel diameters between two genotypes. Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were significantly reduced in Tg mice compared with wild-type mice (35.0 +/- 9.4 versus 61.6 +/- 6.7%, 85.0 +/- 10.2 versus 97.3 +/- 6.7% of the maximum relaxation, respectively). Our data provide the evidence that overproduced NO from endothelium reduces vascular tone and plays a pivotal role in regulation of vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. SR microangiography allows us to evaluate the reactivity in small-sized vessels and appears to be a powerful tool for assessing the microvascular circulation in vivo.     

In-vivo microscopy of the rat endometrial subepithelial capillary plexus during the oestrous cycle and after ovariectomy

Blood flow through the endometrium was visualized by using incident-light fluorescence microscopy and a video image recorded for later detailed analysis. The subepithelial microvascular density was calculated for each day of the oestrous cycle and at 7 days after ovariectomy. The results showed that the microvasculature was significantly more dense at dioestrus I, pro-oestrus, and after ovariectomy than at oestrus, with dioestrus II being in between. Mean capillary path lengths running from arteriole to venule were longest at pro-oestrus, followed by oestrus, dioestrus II, dioestrus I, and shortest after ovariectomy. The results suggest that endometrial growth and regression precede microvascular growth and regression. The technique of in-vivo microscopy provides an important new avenue for investigating the role of local factors in the control of the endometrial microcirculation.     

Microvascular blood viscosity in vivo and the endothelial surface layer

The apparent viscosity of blood in glass tubes declines with decreasing diameter (F?hraeus-Lindqvist effect) and exhibits a distinctive minimum at 6-7 microm. However, flow resistance in vivo in small vessels is substantially higher than predicted by in vitro viscosity data. The presence of a thick endothelial surface layer (ESL) has been proposed as the primary cause for this discrepancy. Here, a physical model is proposed for microvascular flow resistance as a function of vessel diameter and hematocrit in vivo; it combines in vitro blood viscosity with effects of a diameter-dependent ESL. The model was developed on the basis of flow distributions observed in three microvascular networks in the rat mesentery with 392, 546, and 383 vessel segments, for which vessel diameters, network architecture, flow velocity, and hematocrit were determined by intravital microscopy. A previously described hemodynamic simulation was used to predict the distributions of flow and hematocrit from the assumed model for effective blood viscosity. The dependence of ESL thickness on vessel diameter was estimated by minimizing deviations of predicted values for velocities, flow directions, and hematocrits from measured data. Optimal results were obtained with a layer thickness of approximately 0.8-1 microm for 10- to 40-microm-diameter vessels and declined strongly for smaller diameters, with an additional hematocrit-dependent impact on flow resistance exhibiting a maximum for approximately 10-microm-diameter vessels. These results show that flow resistance in vivo can be explained by in vitro blood viscosity and the presence of an ESL and indicate the rheologically effective thickness of the ESL in microvessels.     

Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage

Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH?+?7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.     

Axial shift of erythrocytes in arteries supplying blood to the cerebral cortex

In experiments with rabbits the widths of the axial flows of erythrocytes and of the parietal plasma layers were assessed in pial arterial ramifications supplying the cerebral cortex after their in vivo and in situ fixation under conditions of control and vasodilatation. A strict proportional relationship was revealed between the width of red cell flows and the diameter of pial arteries of 15-200 microns wide. However, the relative plasma volume in the microvessels below 50 microns in diameter was comparatively greater than in the larger vessels. The obtained results prove the feasibility of assessing the microvessels' diameters in tissues where one can see the red cell flow but the vascular walls are invisible. One of the reasons for the lower hematocrit in smaller blood vessels as compared to the larger ones was also elucidated.     

Presence of uterine peroxidase activity in the rat early pregnancy

Peroxidase has been associated with estrogen action in the uterus. This enzyme plays an important role in the control of hydrogen peroxide levels and in catechol estrogen production. Since the uterus, during early pregnancy, is subjected to estrogen and progesterone regulation, we analyzed the changes of peroxidase activity in relation to receptivity and uterine early response to the embryo. Soluble and microsomal peroxidase activity were determined in the rat uterus during the estrus phase and early pregnancy (days 3 through 6). Soluble peroxidase activity increased significantly (p < 0.01) from day 3 (1.50 +/- 0.24) to day 4 (3.5 +/- 0.3) and 5 (5 +/- 0.5 U/mg protein, mean +/- S.D., n = 6) of pregnancy. During day 6, a significant decrease was noted in both the implantation site and the nonimplantation uterine tissue. Microsomal calcium-extractable peroxidase showed a similar pattern, with lower specific activity than, the soluble peroxidase. During estrus, the uterine tissue showed the highest activity of calcium-extracted peroxidase (8.7 +/- 1.35 U/mg protein), statistically greater when compared with days 3, 4, 5 and 6 of pregnancy. In conclusion, high peroxidase activity was associated with uterine receptivity. The decrease of activity on day 6 might be due to a progesterone-estrogen interaction, and consequently, hydrogen peroxide can be utilized for hydroxile production by means of the Fenton reaction. Lipoperoxidation may be necessary for changes in membrane fluidity for embryo attachment to endometrial epithelium.     

Direct observation of epicardial coronary capillary hemodynamics during reactive hyperemia and during adenosine administration by intravital video microscopy

Using high-resolution intravital charge-coupled device video microscopy, we visualized the epicardial capillary network of the beating canine heart in vivo to elucidate its functional role under control conditions, during reactive hyperemia (RH), and during intracoronary adenosine administration. The pencil-lens video-microscope probe was placed over capillaries fed by the left anterior descending artery in atrioventricular-blocked hearts of open-chest, anesthetized dogs paced at 60-90 beats/min (n = 17). In individual capillaries under control conditions, red blood cell flow was predominant during systole or diastole, indicating that the watershed between diastolic arterial and systolic venous flows is located within the capillaries. Capillary flow increased during RH and reached a peak flow velocity (2.1 +/- 0.6 mm/s), twice as high as control (1.2 +/- 0.5 mm/s), with enhancement of intercapillary cross-connection flow and enlargement of diameter (by 17%). With adenosine, capillary flow velocity significantly increased (1.8 +/- 0.7 mm/s). However, the increase in volumetric capillary flow with adenosine estimated from red blood cell velocity and diameter was less than the increase in arterial flow, whereas that during RH was nearly equivalent to the increase in arterial flow. There was a time lag of approximately 1.5 s for refilling of capillaries during RH, indicating their function as capacitance vessels. In conclusion, the coronary capillary network functions as 1) the major watershed between diastolic-dominant arterial and systolic-dominant venous flows, 2) a capacitor, and 3) a significant local flow amplifier and homogenizer of blood supply during RH, but with adenosine the increase in capillary flow velocity was less than the increase in arterial flow.     

Capillary blood flow in the endometrium and myometrium of conscious sheep: effect of catheterization of uterine arteries

Measures of capillary blood flow in the uterine tissues of conscious ewes were obtained by the use of microspheres. Total uterine capillary blood flow was significantly greater (P less than 0.01) at oestrus than at day 8 of the oestrous cycle [69.5 +/- (s.e.m.) 11.9, cf. 15.3 +/- 1.2 ml min-1, n = 7], reflecting increases of a similar order in both the endometrium and the myometrium. At these stages of the oestrous cycle, endometrial capillary blood flow constituted 83.6 and 80.5%, respectively, of the total uterine capillary flow. Following the placement of indwelling catheters in each middle uterine artery there was a decrease in the ratio of endometrial to myometrial capillary blood flow for 3-5 days.     

Correlation of increased concentration of ovine endometrial cyclooxygenase 2 with the increase in PGE2 and PGD2 in the late luteal phase

The effect of intraoviductal embryos on endometrial receptivity was studied by intraendometrial and intrauterine embryo transfer. Five-week-old female ICR mice were mated after superovulation; a vaginal plug confirmed day 1 of pregnancy. On day 4 (90 h after hCG injection), blastocysts were collected and transferred to pseudopregnant female mice and to recipient mice in which the uterotubal junction had been ligated bilaterally on day 1 of pregnancy. Three embryos per uterine horn, a total of six embryos per recipient mouse at days 1-6, were transferred to the endometrium or uterine cavity and implantation and pregnancy rates were calculated. The implantation rate for intraendometrial embryo transfer to recipients of days 3, 5 and 6 was significantly higher for uterotubal junction-ligated mice (72.2, 20.8 and 9.7%, respectively) than for pseudopregnant mice (55.0, 8.3 and 0.0%, respectively). The implantation rate for intrauterine embryo transfer to recipients at days 2, 5 and 6 was significantly higher for uterotubal junction-ligated mice (11.1, 25.0 and 8.3%, respectively) than for pseudopregnant mice (0.0, 3.3 and 0.0%, respectively). Uterotubal junction-ligated mice achieved implantation and bore neonates by intrauterine embryo transfer on days 2 and 6, whereas no implantation was achieved in pseudopregnant mice. The difference in implantation rate could not be explained by a difference in progesterone concentration between the groups. The distribution of proliferating cells in the endometrium was also studied immunohistochemically by use of anti-proliferating cell nuclear antigen (PCNA) antibody in the recipient mice. PCNA-positive cells were more abundant in uterotubal junction-ligated mice and demonstrated a marked extension from the epithelium to the stroma over time, in contrast to those in pseudopregnant mice. These findings indicate that an intraoviductal embryo exerts a biological effect by sending a signal to the endometrial epithelium and stroma, thus facilitating endometrial receptivity to the embryo and improving the rate of implantation.     

Inhibition of rat embryo implantation in the gossypol-treated uterine horn

We have developed a method to test the effect of gossypol on prevention of embryo implantation in the uterine horn. On the day of proestrus, gossypol (at a dose of 50, 100, 150, 200 and 500 mug per uterine horn was injected directly into the lumen of the right uterine horn. The left uterine horn was injected with 100 mul buffer. The rats were then mated with fertility proven males on the same day. The day of sperm-positive vaginal smear was designated as Day 0 of pregnancy. The number of implantation sites in both control and gossypol-treated horns was examined on Day 8 of pregnancy by laparotomy. The number of pups born was counted after parturition. At laparotomy, the percentages of pregnant animals with positive implantation sites in the gossypol-treated uterine horn (at a dose of 500, 200, 150, 100 and 50 mug per uterine horn) were 0, 0, 0, 10 and 44%, respectively. By contrast, implantation sites were present in 100% of the control horns of the same rats. The average numbers of total implantation sites in both horns vs the number of pups born to gossypol-treated animals using 500, 200, 150, 100, and 50 mug doses were 5.60 +/- 1.25 vs 4.00 +/- 1.00, 5.83 +/- 1.30 vs 4.70 +/- 1.10, 5.80 +/- 1.10 vs 5.50 +/- 1.20, 11.50 +/- 1.00 vs 9.50 +/- 1.50 and 11.67 +/- 1.20 vs 9.30 +/- 1.20, respectively. Gossypol metabolite completely inhibited embryo implantation when administered at 5.30 mug per uterine horn. The potency of the gossypol metabolite in preventing embryo implantation is estimated to be at least 28 times higher than the parent compound.     

Spatial and temporal control of angiogenesis and arterialization using focal applications of VEGF164 and Ang-1

Microvascular networks undergo patterning changes that determine and reflect functional adaptations during tissue remodeling. Alterations in network architectures are a result of complex and integrated signaling events. To understand how two growth factor signals interact to stimulate angiogenesis and arterialization, we engineered spatially directed microvascular pattern changes in vivo by using combinations of focally delivered exogenous growth factors. We implanted microdelivery beads containing recombinant vascular endothelial growth factor-164 (VEGF(164)) and recombinant angiopoietin-1* (Ang-1*) into the dorsal subcutaneous tissue of fully anesthetized male Fischer 344 rats implanted with backpack window chambers, and we quantified vascular patterning changes by using intravital microscopy, a combination of architectural metrics, and immunohistochemistry. Focal delivery of VEGF(164) caused spatially directed increases in both the total number and the density of vessels with diameters <25 microm 7 days after microbead implantation. Increases were maintained out to 14 days but were reduced to control values by day 21. The addition of Ang-1* on day 7 maintained these increases out to day 21, induced vessel order ratios comparable to control levels, and was accompanied by increases in the length density of smooth muscle alpha-actin-positive vessels. We achieved spatial control of patterning changes in vivo by using multisignal stimulation via focal delivery of exogenous growth factor combinations and conclude that Ang-1* administered subsequent to VEGF(164) stimulation induces vascular growth while maintaining a network pattern consistent with native patterns that persist in the presence of vehicle control stimulation.     

Chorioallantoic placenta formation in the rat: II. Angiogenesis and maternal blood circulation in the mesometrial region of the implantation chamber prior to placenta formation.

Rat gestation sites were examined on days 7 through 9 of pregnancy by light microscopy and transmission and scanning electron microscopy to determine the extent of vascular modifications in the vicinity of the mesometrial part of the implantation chamber (mesometrial chamber). At a later time, the mesometrial chamber is, in conjunction with the uterine lumen, the site of chorioallantoic placenta formation. On day 7, in the vicinity of the mesometrial chamber, vessels derived from a subepithelial capillary plexus and venules draining the plexus were dilating. By early day 8, this network of thin-walled dilated vessels (sinusoids) was further enlarged and consisted primarily of hypertrophied endothelial cells with indistinct basal laminas. Sinusoids were frequently close to the mesometrial chamber's luminal surface which was devoid of epithelial cells but was lined by decidual cell processes and extracellular matrix. By late day 8, cytoplasmic projections of endothelial cells extended between healthy-appearing decidual cells and out onto the mesometrial chamber's luminal surface, and endothelial cells were sometimes found on the luminal surface indicating that endothelial cells were migrating. The presence of maternal blood cells in the mesometrial chamber lumen suggested that there was continuity between the chamber and blood-vessel lumens. On day 9, the mesometrial chamber was completely lined with hypertrophied endothelial cells, and sinusoid lumens were clearly continuous with the lumen of the mesometrial chamber. Mesometrial sinusoids and possibly the mesometrial chamber lumen were continuous with vessels in vicinity of the uterine lumen that were fed by mesometrial arterial vessels. Clearing of the mesometrial chamber lumen during perfusion fixation via the maternal vasculature indicated the patency of this luminal space and its confluence with mesometrial arterial vessels and sinusoids. The conceptus occupied an antimesometrial position in the implantation chamber on days 7 through 9, and it was not in direct contact with uterine tissues in the vicinity of the mesometrial chamber. These observations suggest that angiogenesis, not trophoblast invasion or decidual cell death, plays a major role in the opening of maternal vessels into the mesometrial chamber lumen before the formation of the chorioallantoic placenta.     

Expression and cellular distribution of NADPH-diaphorase and nitric oxide synthases in the porcine uterus during early pregnancy

Nitric oxide plays a key role in the regulation of various female reproductive processes such as ovulation, implantation and myometrial relaxation. The aim of the present study was to determine the histochemical activity and cellular localization of NADPH-d in the porcine uterus during early pregnancy, including the implantation period. Tissue samples collected from the pig uteri on days 5, 10, 12, 15 and 17 of pregnancy were stained histochemically for NADPH-d activity and immunohistochemically for NOS isoforms localization. In the luminal epithelium a significant increase of NADPH-d activity was observed on days 5-12 of pregnancy. On day 17 of pregnancy, two different staining patterns were observed: 1) a significant (p0.001) decrease in NADPH-d activity at the site of implantation and 2) the high NADPH-d activity at inter-implantation regions. The endometrial glands showed a significant (p0.001) increase in NADPH-d staining with high activity in individual glands. The arterial endothelium expressed stronger NADPH-d staining compared with venous vessels. Immunoreactivity of eNOS was similar to NADPH-d staining but no optical differences in the intensity of staining were observed. Clear iNOS immunoreactivity was detected in the luminal epithelium, endometrial stroma and individual endometrial glands. The vascular endothelium displayed weak iNOS staining.     

Studies on the microvascularization of the digestive tract by scanning electron microscopy of vascular corrosion casts. 2. Bile duct in guinea pigs.

The microvascularization of the bile duct was studied in 20 adult guinea pigs (Cavia porcellus) using microvascular corrosion casts in the scanning electron microscope. The main supplying and draining vessels are located in the adventitial layer; from there they form the subepithelial capillary network. The microangioarchitecture of the common bile duct is reminiscent of that of the cystic and hepatic ducts. The diameter of these ducts is 1,000 microns on average. The microvascular arrangement in the bile duct suggests a probable involvement of the capillaries in the absorption of bile hormones.     

Extracellular matrix remodelling in rat endometrium during early pregnancy: The role of fibronectin and laminin

The endometrial extracellular matrix (ECM) remodelling has a crucial role in the establishment of a successful pregnancy. In addition to its basic function such as regulation of cell function, differentiation, migration, proliferation, the substantial alterations in the endometrial ECM may play a specific role in the trophoblast invasion, placentation, cell death and formation of the proper and functional implantation chamber around the embryo. In the present study, immunolocalizations of fibronectin and laminin were determined using avidin-biotin complex-peroxidase in rat implantation sites during 7-10 days of pregnancy. Both proteins were present in the basal membrane of blood vessels and in decidual matrix whereas they were absent or had very weak reactivity in the primary decidual zone on day 7. When placentation has begun, the immunoreactivity of both proteins was increased in the placental bed and in the basal membrane of blood vessels of the mesometrial region. The immunolocalization of both proteins seemed to be decreased in the antimesometrial decidua, however, it was increased in the mesometrial decidual matrix on days 9 and 10. Therefore, it could be suggested laminin and fibronectin demonstrating dynamic expressions in relation with the morphological differentiation of endometrial stroma may play crucial roles in the control of trophoblast adhesion and invasion, in placentation and angiogenesis, in the determination of cell shape and fate thus contributing the endometrial receptivity and a successful pregnancy.     

Expression of stathmin family genes in the murine uterus during early pregnancy

Stathmin, a cytosolic phosphoprotein that regulates microtubule dynamics during cell-cycle progression, is abundantly expressed at embryo implantation sites in rats. Here, we characterized the expression of stathmin and its family genes in the murine uterus during the peri-implantation period. Stathmin protein was expressed in the glandular and luminal epithelium, blood vessels, and stromal cells on day 3 of pregnancy. On the day of implantation (day 5), stathmin was mainly localized in blood vessels in the endometrium. On day 7, intense stathmin expression was limited to capillary vessels and secondary decidual cells. Stathmin expression was higher at implantation sites than at uterine segments between implantation sites and increased during oil-induced decidualization. Although the artificially-induced deciduoma weights and number of implantation sites were similar between stathmin-knockout (KO) and wild-type (WT) mice, the stathmin-KO mice had fewer newborn pups (reduced by 30%). The expression of alkaline phosphatase, desmin, and cyclin D3 was attenuated in decidual zones of stathmin-KO mice. Messenger RNA level of the stathmin family gene, SCG10, was high at the time of decidualization in WT and stathmin-KO mice. In contrast, the others of stathmin family members, SCLIP and RB3 were highly expressed in stathmin-KO mice compared to WT mice. These results suggest that stathmin and stathmin family genes are expressed in the murine endometrium with enhanced expression in the implantation or the decidualization process.