The Challenge of Creating Lordosis in High-Grade Dysplastic Spondylolisthesis.

High-grade dysplastic spondylolisthesis (HGDS) is a subset of L5-S1 spondylolisthesis that occurs due to dysmorphic anatomy at the lumbosacral junction, often resulting in sagittal imbalance. Enhanced understanding of global sagittal alignment has led many to preferentially treat HGDS with reduction and fusion to restore sagittal balance. The purpose of this article is to review published surgical techniques for obtaining sagittal correction in HGDS and to evaluate the current evidence regarding the associated surgical complications.

Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery.

AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.

Molecular and functional aspects of menstruation in the macaque.

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Early histological changes in the porcine aortic media after thoracic stent-graft implantation.

PURPOSE: To describe the histological findings in the aortic wall 5 days after thoracic endovascular aortic repair (TEVAR) in a porcine model. METHODS: Two overlapping stent-grafts were implanted in each of 6 juvenile pigs, covering the entire descending thoracic aorta (DTA). On the 5(th) postoperative day, tissue samples were taken from the DTA in each animal. Medial thickness and medial necrosis were quantified and compared to measurements from the aortas of 6 control animals. RESULTS: Significant medial thinning was observed in stent-covered regions in the test animals. At the proximal landing zone, aortic wall thickness changed from 1387±68 to 782±74 µm within the covered aortic segment (p = 0.028); at the distal landing site, the wall thickness was 365±67 µm within the stent and 501±57 µm distally (p = 0.028). In the overlap zone, the aortic wall measured 524±122 vs. 1053±77 µm in native controls (p = 0.004). Aortic thickness proximal to the graft did not differ from the proximal region of native aortas (1468±96 vs. 1513±80 µm, p = 0.423), but the aorta was significantly thinner distal to the stent (707±38 vs. 815±52 µm, p = 0.004). Laminar necrosis constituted 38%±7% of the media in the proximal landing zone, 54%±4% in the overlap zone, and 46%±13% in the distal landing zone. CONCLUSION: In this porcine model, significant medial thinning and necrosis of the stented aorta was observed. The findings suggest an early phase of vulnerability of the aortic wall, before scarring and adaptive changes have strengthened the residual aorta.

Dynamic regulation of Wnt7a expression in the primate endometrium: implications for postmenstrual regeneration and secretory transformation.

Despite the vital physiological role of endometrial regeneration during the menstrual cycle and the various pathological implications of abnormal growth of endometrial epithelial cells, the local factors and regulatory mechanisms involved in endometrial regeneration and growth have not been well characterized. Here, we examine the pattern, hormone dependence, and potential functions of Wnt7a (wingless-type MMTV integration site family member 7a), which is known to play a critical role in the formation of the mouse endometrial epithelium during embryonic development, in both human and artificially cycling rhesus macaque endometrium, and using a potent Wnt-antagonist in a mouse model of endometrial regeneration. Wnt7a transcript levels were examined using quantitative real-time PCR and in situ hybridization, and immunohistochemistry was performed to detect Ki-67 and 3,5-bromodeoxyuridine. Stringent, fully conditional Wnt inhibition was achieved by adenoviral expression of Dickkopf-1 during artificial endometrial regeneration in mice. In macaques, Wnt7a expression was confined to the newly formed luminal epithelium (LE) and upper glands during the postmenstrual repair phase. The signal increased in the LE during the proliferative phase but decreased in the upper glands and was undetectable in the glands by the late proliferative phase. Interestingly, Wnt7a was completely suppressed in the LE and remained undetectable in other cell types after 7 d of progesterone treatment. The pattern of Wnt7a expression in the human endometrium was similar to that in macaques. Blockade of Wnt signaling during endometrial regeneration in mice resulted in a dramatic delay in reepithelialization and degeneration of glands and LE. These results strongly suggest, for the first time, a role for Wnt7a in postmenstrual regeneration and proliferation of endometrial glands and LE in primates, and its dramatic suppression by progesterone is likely essential for secretory transformation of the epithelium.

Staged approach prevents spinal cord injury in hybrid surgical-endovascular thoracoabdominal aortic aneurysm repair: an experimental model.

BACKGROUND: In a porcine model, we investigated the impact of sudden stent graft occlusion of thoracic intercostal arteries after open lumbar segmental artery (SA) ligation. METHODS: After randomization into two groups, 20 juvenile Yorkshire pigs (27.1±0.6 kg) underwent open lumbar SA sacrifice (T13-L5) followed by endovascular coverage of all thoracic SAs (T4-T12) at 32°C, either in a single operation (group 1) or in two stages separated by seven days (group 2). Collateral network pressure (CNP) was monitored by catheterization of the SA L1, and postoperative hind limb function was assessed using a modified Tarlov score. RESULTS: The CNP in group 1 decreased to 34% of baseline, whereas CNP after lumbar SA ligation in group 2 fell to 55% of baseline (74±2.4 to 25±3.6 mm Hg vs 74±4.5 to 41±5.5 mm Hg; p<0.0001). Subsequent thoracic stenting (group 2) led to another significant but milder drop (p=0.002 versus stage 1) from the restored CNP (71±4.2 to 54±4.9 mm Hg). Five of ten pigs in group 1 suffered paraplegia, in contrast to none in group 2 (median Tarlov score 6, vs 9; p=0.0031). Histopathologic analysis showed more severe ischemic damage to the lower thoracic (p=0.05) and lumbar spinal cord (p=0.002) in group 1. CONCLUSIONS: These results underline the potential of the staged approach in hybrid procedures. Furthermore they highlight the need for established adjuncts for preventing paraplegia in hybrid and pure stent-graft protocols in which sudden occlusion of multiple SAs occurs.

The collateral network concept: a reassessment of the anatomy of spinal cord perfusion.

OBJECTIVE: Prevention of paraplegia after repair of thoracoabdominal aortic aneurysm requires understanding the anatomy and physiology of the spinal cord blood supply. Recent laboratory studies and clinical observations suggest that a robust collateral network must exist to explain preservation of spinal cord perfusion when segmental vessels are interrupted. An anatomic study was undertaken. METHODS: Twelve juvenile Yorkshire pigs underwent aortic cannulation and infusion of a low-viscosity acrylic resin at physiologic pressures. After curing of the resin and digestion of all organic tissue, the anatomy of the blood supply to the spinal cord was studied grossly and with light and electron microscopy. RESULTS: All vascular structures at least 8 µm in diameter were preserved. Thoracic and lumbar segmental arteries give rise not only to the anterior spinal artery but to an extensive paraspinous network feeding the erector spinae, iliopsoas, and associated muscles. The anterior spinal artery, mean diameter 134 ± 20 µm, is connected at multiple points to repetitive circular epidural arteries with mean diameters of 150 ± 26 µm. The capacity of the paraspinous muscular network is 25-fold the capacity of the circular epidural arterial network and anterior spinal artery combined. Extensive arterial collateralization is apparent between the intraspinal and paraspinous networks, and within each network. Only 75% of all segmental arteries provide direct anterior spinal artery-supplying branches. CONCLUSIONS: The anterior spinal artery is only one component of an extensive paraspinous and intraspinal collateral vascular network. This network provides an anatomic explanation of the physiological resiliency of spinal cord perfusion when segmental arteries are sacrificed during thoracoabdominal aortic aneurysm repair.

The collateral network concept: remodeling of the arterial collateral network after experimental segmental artery sacrifice.

OBJECTIVE: A comprehensive strategy to prevent paraplegia after open surgical or endovascular repair of thoracoabdominal aortic aneurysms requires a thorough understanding of the response of the collateral network to extensive segmental artery sacrifice. METHODS: Ten Yorkshire pigs underwent perfusion with a low-viscosity acrylic resin. With the use of cardiopulmonary bypass, 2 animals each were perfused in the native state and immediately, 6 hours, 24 hours, and 5 days after sacrifice of all segmental arteries (T4-L5). After digestion of surrounding tissue, the vascular cast of the collateral network underwent analysis of arterial and arteriolar diameters and the density and spatial orientation of the vasculature using light and scanning electron microscopy. RESULTS: Within 24 hours, the diameter of the anterior spinal artery had increased significantly, and within 5 days the anterior spinal artery and the epidural arterial network had enlarged in diameter by 80% to 100% (P < .0001). By 5 days, the density of the intramuscular paraspinous vessels had increased (P < .0001), a shift of size distribution from small to larger arterioles was seen (P = .0002), and a significant realignment of arterioles parallel to the spinal cord had occurred (P = .0005). CONCLUSIONS: Within 5 days after segmental artery occlusion, profound anatomic alterations in the intraspinal and paraspinous arteries and arterioles occurred, providing the anatomic substrate for preservation of spinal cord blood flow via collateral pathways.

Long-term outcome after aortic arch replacement with a trifurcated graft.

OBJECTIVE: We describe the long-term results of aortic arch replacement using a trifurcated graft, including an assessment of survival, neurologic complications, and graft patency. METHODS: A retrospective review was conducted on data from 206 consecutive patients (125 male; median age, 67 years; range, 20-87 years) who had a trifurcated graft used for aortic arch replacement between September 1999 and September 2009. Seventy-four patients (35.9%) had chronic dissection, 68 patients (33.0%) had atherosclerotic aneurysms, and 39 patients (18.9%) had degenerative disease. Ninety-one patients (44.2%) had undergone previous cardiac surgery. RESULTS: An elephant trunk was placed in 190 patients (92.2%) and completed in 101 patients (53.1%), with an interval of less than 365 days between stages in 94 of 101 patients. Hospital mortality was 6.8% (14/206). Adverse outcome (death/stroke within the first year postoperatively) occurred in 27.7% of patients (57/206; 50 deaths/7 strokes). Among 152 1-year survivors, the annual rates of transient ischemic attack and stroke were 0.85% and 1.1%, respectively. At 6 years, 75% of patients were still alive, compared with 92% in a matched New York State control population (P < .001). Follow-up computed tomography scans (189 studies in 176/206 patients [85.4%]) revealed 100% patency of the trifurcated graft limbs at a mean of 2.3 years. CONCLUSIONS: Aortic arch replacement using a trifurcated graft is highly durable, with excellent patency in the branch grafts, and is associated with a low incidence of cerebral embolization. However, the long-term outcome in these patients is compromised by extensive comorbidities.

Predicting the risk of paraplegia after thoracic and thoracoabdominal aneurysm repair.

BACKGROUND: Endovascular repair of descending thoracic and thoracoabdominal aortic aneurysms is an appealing alternative to the standard surgical approach, but precludes revascularization of segmental arteries (SAs). For safer surgical and endovascular repairs, an accurate prediction of the risk of paraplegia in relation to the extent of SA sacrifice is needed. METHODS: From January 1994 to October 2008, 609 patients (mean age, 63 ± 14 years) underwent surgical descending thoracic or thoracoabdominal aortic aneurysm repair without SA reimplantation. Three hundred seventy-six patients (62%) were male; 159 (26%) had urgent or emergent operation; 199 (33%) had previous aortic surgery. Somatosensory- or motor-evoked potential monitoring and cerebrospinal fluid drainage were routinely performed. RESULTS: Hospital mortality was 10.7% (65 patients). Spinal cord injury (SCI) occurred in 3.4% (21 patients). The extent of resection-expressed as the number of SAs sacrificed (p = 0.007)-and the need for visceral artery reimplantation (p = 0.03) were independent risk factors for paraplegia. Further analysis identified four risk groups (p < 0.0001): fewer than 8 SAs sacrificed (group A, SCI = 1.2%); sacrifice of 8 to 12 SAs with proximal origin in the upper thorax (group B, SCI = 3.7%); 8 to 12 SAs sacrificed beginning in the lower thorax (group C, SCI = 15.4%); and 13 or more SAs sacrificed (group D, SCI = 12.5%). This four-group model more accurately predicts SCI risk than the Crawford classification (goodness of fit c statistic: 0.748 versus 0.640). CONCLUSIONS: The extent of SA sacrifice is the most powerful predictor of paraplegia risk. For aneurysms of moderate extent, a more distal location involving the abdominal aorta increases the risk of spinal cord injury. Sacrifice of fewer than 8 SAs is associated with a very low paraplegia risk regardless of location.

Experimental two-stage simulated repair of extensive thoracoabdominal aneurysms reduces paraplegia risk.

BACKGROUND: In a pig model, we compared spinal cord injury after extensive segmental artery (SA) sacrifice in a single stage with recovery after a two-stage procedure: lumbar artery followed by thoracic SA sacrifice. METHODS: Twenty juvenile Yorkshire pigs were randomly assigned to undergo extensive SA sacrifice at 32 degrees C in a single operation (group 1, n = 10), or thoracic SA ligation 7 days after lumbar artery sacrifice (group 2, n = 10). Spinal cord perfusion pressure (SCPP) was monitored using a catheter placed in the distal stump of L1. Hind limb function was evaluated intraoperatively using motor-evoked potentials and for 5 days postoperatively using a modified Tarlov score. RESULTS: Motor-evoked potentials were intact in all pigs until 1 hour after surgery. All pigs in group 2 fully recovered hind limb function, whereas 40% in group 1 experienced paraplegia (median Tarlov scores 9 versus 7; p = 0.004). Group 1 SCPP fell to 28 +/- 6 mm Hg after SA sacrifice, compared with 44 +/- 8 mm Hg in group 2 (p < 0.0001). After sacrifice of all residual SAs, SCPP in group 2 remained consistently greater than 85% of baseline, significantly higher than group 1 SCPP from end clamping until 72 hours (p = 0.0002). Histopathologic analysis showed more severe ischemic damage to the lower thoracic (p < 0.001) and lumbar spinal cord (p = 0.01) in group 1. CONCLUSIONS: In contrast with the single-stage approach, a two-stage procedure, starting with ligation of six or fewer lumbar SAs, leads to only a mild drop in SCPP and stimulates vascular remodeling, minimizing the impact of subsequent SA sacrifice on spinal cord function. The greater safety of extensive SA sacrifice when undertaken in two stages has important implications for endovascular and hybrid aneurysm repair.

Long-term survival after open repair of chronic distal aortic dissection.

BACKGROUND: The optimal treatment of chronic distal aortic dissection remains controversial, with endovascular stent-graft techniques challenging traditional surgery. METHODS: From January 1994 to April 2007, 104 patients (82 male, median age 60.5 years) with chronic distal aortic dissection underwent surgical repair, 0 to 21 years after initial diagnosis of acute type A or B dissection (median 2.1 years). Twenty-three (22%) patients underwent urgent-emergent surgery. Mean aortic diameter was 6.9 +/- 1.4 cm. Indications for surgery, other than aortic expansion, were pain in 6 (6%) patients, malperfusion in 6 (6%), and rupture in 11 (11%). Forty-nine (47%) had previous cardioaortic surgery (29% dissection-related), 21 (20%) had coronary artery disease, 12 (12%) had Marfan syndrome, and 4 (4%) were on chronic dialysis. Twenty-six (25%) had a thrombosed false lumen. Thirty (29%) patients required reimplantation of visceral arteries; 8.3 +/- 2.7 segmental artery pairs were sacrificed. RESULTS: Hospital mortality was 9.6% (10 patients). Paraplegia occurred in 5 (4.8%). Twenty-seven patients (26%) experienced adverse outcome (death within one year, paraplegia, stroke, or dialysis). Adverse outcome was associated with atheroma (p = 0.04, odds ratio = 4.3). Survival was 78% at 1, 68% at 5, and 59% at 10 years (average follow-up, 7.7 +/- 4.1 years). Freedom from distal aortic reoperation was 99% at 1, 93% at 5, and 83% at 10 years. After one year, patients enjoyed longevity equivalent to a normal age-sex matched population (standardized mortality ratio = 1.38, p = 0.23). By multivariate analysis, atheroma (p = 0.0005, relative risk = 9.32) and age (p = 0.0003, relative risk = 1.15/year) were risk factors for long-term survival. CONCLUSIONS: The efficacy of open repair for distal chronic dissection is highlighted by normal survival after the first year, and a low reoperation-reintervention rate.

Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques.

BACKGROUND: Ulipristal (UPA; CDB-2914) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. STUDY DESIGN: Short lengths of Silastic tubing either empty (n=3) or containing UPA (n=5) were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. RESULTS: During treatment, animals with an empty IUS menstruated for a mean total of 11.66+/-0.88 days, while UPA-IUS treated animals bled for only 1+/-0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. CONCLUSIONS: In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal.

VEGF blockade inhibits angiogenesis and reepithelialization of endometrium.

Despite extensive literature on vascular endothelial growth factor (VEGF) expression and regulation by steroid hormones, the lack of clear understanding of the mechanisms of angiogenesis in the endometrium is a major limitation for use of antiangiogenic therapy targeting endometrial vessels. In the current work, we used the rhesus macaque as a primate model and the decidualized mouse uterus as a murine model to examine angiogenesis during endometrial breakdown and regeneration. We found that blockade of VEGF action with VEGF Trap, a potent VEGF blocker, completely inhibited neovascularization during endometrial regeneration in both models but had no marked effect on preexisting or newly formed vessels, suggesting that VEGF is essential for neoangiogenesis but not survival of mature vessels in this vascular bed. Blockade of VEGF also blocked reepithelialization in both the postmenstrual endometrium and the mouse uterus after decidual breakdown, evidence that VEGF has pleiotropic effects in the endometrium. In vitro studies with a scratch wound assay showed that the migration of luminal epithelial cells during repair involved signaling through VEGF receptor 2-neuropilin 1 (VEGFR2-NP1) receptors on endometrial stromal cells. The leading front of tissue growth during endometrial repair was strongly hypoxic, and this hypoxia was the local stimulus for VEGF expression and angiogenesis in this tissue. In summary, we provide novel experimental data indicating that VEGF is essential for endometrial neoangiogenesis during postmenstrual/postpartum repair.

Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality.

BACKGROUND: Chronic kidney disease (CKD) is recognized as an independent cardiovascular disease (CVD) risk state, particularly in the elderly, and has been defined by levels of estimated glomerular filtration rate (eGFR) and markers of kidney damage. The relationship between CKD and CVD in younger and middle-aged adults has not been fully explored. METHODS: Community volunteers completed surveys regarding past medical events and underwent blood pressure and laboratory testing. Chronic kidney disease was defined as an eGFR <60 mL x min(-1) x 1.73 m(-2) or urine albumin-creatinine ratio (ACR) > or =30 mg/g. Premature CVD was defined as self-reported myocardial infarction or stroke at <55 years of age in men and <65 years of age in women. Mortality was ascertained by linkage to national data systems. RESULTS: Of 31 417 participants, the mean age was 45.1 +/- 11.2 years, 75.5% were female, 36.8% African American, and 21.6% had diabetes. A total of 20.6% were found to have CKD, with the ACR and eGFR being the dominant positive screening tests in the younger and older age deciles, respectively. The prevalences of premature myocardial infarction (MI), stroke, or death, and the composite were 5.3%, 4.7%, 0.8%, 9.2%, and 2.5%, 2.2%, 0.2%, 4.2% for those with and without CKD, respectively (P < .0001 for composite). Multivariable analysis found CKD (OR 1.44, 95% CI 1.27-1.63), age (OR 1.05 [per year], 95% CI 1.04-1.06), hypertension (OR 1.61, 95% CI 1.40-1.84), diabetes (OR 2.03, 95% CI 1.79-2.29), smoking (OR 1.91, 95% CI 1.66-2.21), and less than high school education (OR 1.59, 95% CI 1.37-1.85) as the most significantly associated factors for premature CVD or death (all P < .0001). Survival analysis found those with premature MI or stroke and CKD had the poorest short-term survival over the next 3 years after screening. CONCLUSIONS: Chronic kidney disease is an independent predictor of MI, stroke, and death among men and women younger than age 55 and 65 years, respectively. These data suggest the biologic changes that occur with kidney failure promote CVD at an accelerated rate that cannot be fully explained by conventional risk factors or older age. Screening for CKD by using both the ACR and eGFR can identify younger and middle-aged individuals at high risk for premature CVD and near-term death.

Antiprogestin-releasing intrauterine devices: a novel approach to endometrial contraception.

Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists [antiprogestins (APs)] are known to suppress the endometrium, induce amenorrhea and inhibit fertility, AP-releasing IUDs (AP-IUDs) may provide an effective contraceptive that also controls endometrial bleeding. Here, we assessed the effects of empty (blank) vs. AP-IUDs (ZK 230 211) on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP-IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, P withdrawal bleeding was prevented, and estradiol (E(2))-dependent proliferation was suppressed by the AP-IUDs. In sum, AP-IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of E(2) on endometrial proliferation, as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding.

Assessment of menstruation in the vervet (Cercopithecus aethiops).

Vervet monkeys (Chlorocebus aethiops) are Old World nonhumans that display attenuated menstruation that requires detection by vaginal swab. The physiology underlying attenuated menstruation in this species has not been previously studied. To fill this gap, we evaluated endometrial cell proliferation, steroid receptor localization and expression of menstruation-associated matrix metalloproteinase (MMP) enzymes in vervets during natural and artificial menstrual cycles. The artificial cycles were induced by sequentially treating ovariectomized animals with estradiol (E(2)) and progesterone (P). Because menstrual flow is exceptionally light in this species, menses was detected by vaginal swab. We found that both natural and artificially cycled animals menstruated 3-5 days after the decline of P at the end of the cycle. As in other primates, P withdrawal at the end of artificial cycles triggered endometrial expression of MMPs, including MMP-1, 2, 3, 7, 10, 11, 13 and 26 transcripts. In both the natural and artificial menstrual cycle, menstrual sloughing was restricted to the upper one-fourth of the endometrium, and MMP-1 and 2 were strongly expressed by the stroma of the sloughing zone. MMP-7 was localized in the endometrial glands during late menses. As in macaques, epithelial cell proliferation was localized to the functionalis zone during the estrogen-dominated proliferative phase and to the basalis zone glands during the P-dominated secretory phase. Regulation of estrogen and progestin (or estradiol and progesterone) receptors was similar to that reported for macaques. Because strong similarities exist between the endometrium of vervets, macaques and women, we conclude that vervets can provide a useful animal model for studies on hormone regulation of menstruation.