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Objective: To describe effects of non‐ablative erbium‐doped:yttrium‐aluminium‐garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. Design: Animal experimental, randomised, sham and estrogen‐treatment controlled study with blinding for primary outcome. Setting: KU Leuven, Belgium. Sample: Twenty‐four ewes. Methods: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1‐month interval; three sham manipulations with a 1‐month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. Main outcome measures: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. Results: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser‐treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen‐substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. Conclusions: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT. Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT. [ABSTRACT FROM AUTHOR]

An abstract of the article "Clinical courses variability of monochorionic twins based on a different placental vascular architecture," by L. Haslik and colleagues is presented.

Introduction and Hypothesis: The main risk factor for pelvic floor disorders is vaginal delivery, which may cause levator ani muscle (LAM) injury and denervation. LAM includes pubovisceral muscle (PVM, pubococcygeus), puborectalis muscle (PRM), and iliococcygeus muscle. We hypothesize that primiparous women with low pelvic floor muscle contraction have a reduced PVM cross-sectional area (CSA) compared to nulliparous women., Methods (sample Size and Statistical Approaches): This single-centre prospective observational study compared healthy nulliparous (n = 40) to primiparous (n = 40) women after vaginal delivery without LAM avulsion and Oxford score ≤ 3. Demographics, questionnaires (ICIQ-UI-SF, OAB-Q-SF, PISQ-12), POP-Q, Oxford score, ultrasound measurements (minimal anteroposterior and lateral diameters, hiatal area, PRM thickness, levator-urethra gap) and magnetic resonance imaging (MRI)-PVM CSA were evaluated. Normality was tested, and an appropriate test was used to compare the groups. Power calculation suggested 40 participants per group., Results: The primiparous group was older, had a higher BMI, and their hiatal area on ultrasound at contraction was larger compared to the nulliparous group. The CSA of the left-sided PVM (1.15 ± 0.50 cm 2 ) was larger compared to the right side (1.03 ± 0.50 cm 2 ), p = 0.02 in nulliparous women. The PVM CSA of primiparous women with low Oxford score was reduced compared to nulliparous (0.87 ± 0.30 versus 1.09 ± 0.50 cm 2 , p = 0.006). The intra-rater reliability for PVM CSA had an ICC of 0.90 and inter-rater ICC of 0.77., Conclusions: Primiparous women after vaginal delivery with low pelvic floor contraction force had reduced PVM CSA on MRI images compared to nulliparous women., (© 2024. The Author(s).)

Objectives: The good healing of the hysterotomy after cesarean section is important for subsequent pregnancies. However, the factors which improve this healing have not been completely described, yet. In this study, we focused on factors which may affect healing of hysterotomy within one year after delivery, such as menstruation, breastfeeding, and the use of the contraception., Material and Methods: Following delivery, total of 540 women were invited for three consecutive visits at six weeks, six months, and 12 months postpartum. The presence of menstruation, frequency of breastfeeding and contraception use were recorded. The scar was evaluated by vaginal ultrasound as already described. The impact of menstruation, breastfeeding, and contraception method on presence of niche was evaluated., Results: The presence of menstruation increased odds to have niche by 45% (CI 1.046-2.018, p = 0.026). Secondarily, our results demonstrated a statistically significant protective effect of breastfeeding on the incidence of niche with OR 0.703 (CI 0.517-0.955, p = 0.024). Breastfeeding decreases odds to have niche by 30%. Also, the use of gestagen contraception lowered the odds by 40% and intrauterine device (IUD) or combine oral contraceptive (COC) by 46.5%. The other possibly intervening factors were statistically controlled., Conclusions: Amenorrhea, breast-feeding and progesterone-contraceptive decreases the risk of uterine niche within one year follow up.

Objective: To evaluate the host- and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with the response to polypropylene (PP) mesh., Design: In vivo animal experiment., Setting: KU Leuven Center for Surgical Technologies., Population: Fourteen parous female Mule sheep., Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical study protocol performed previously., Main Outcome Measures: Gross necropsy, host response and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Data are reported as mean ± standard deviation (SD) or standard error of the mean (SEM)., Results: Gross necropsy revealed no implant-related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm SEM [p =0.019]) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh(0.99 ± 0.78 SD, score 0-4) at 180-days., Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load-bearing capacity. If these results are also observed at longer follow-up in-vivo, a clinical study using P4HB for vaginal POP surgery may be warranted to demonstrate efficacy., Tweetable Abstract: Degradable vaginal P4HB implant might be a solution for treatment of POP., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe., Design: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome., Setting: KU Leuven, Belgium., Sample: Twenty-four ewes., Methods: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy., Main Outcome Measures: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs., Results: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria., Conclusions: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes., Tweetable Abstract: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT., (© 2020 John Wiley & Sons Ltd.)

Introduction and Hypothesis: Er:YAG laser is frequently used in dermatology and gynecology. Clinical studies document high satisfaction rates; however, hard data on the effects at the structural and molecular levels are limited. The aim of this systematic review was to summarize current knowledge about the objective effects of non-ablative Er:YAG laser on the skin and vaginal wall., Methods: We searched MEDLINE, Embase, Cochrane, and the Web of Science. Studies investigating objectively measured effects of non-ablative Er:YAG laser on the skin or vaginal wall were included. Studies of any design were included. Owing to the lack of methodological uniformity, no meta-analysis could be performed and therefore results are presented as a narrative review., Results: We identified in vitro or ex vivo studies on human cells or tissues, studies in rats, and clinical studies. Most studies were on the skin (n = 11); the rest were on the vagina (n = 4). The quality of studies is limited and the settings of the laser were very diverse. Although the methods used were not comparable, there were demonstrable effects in all studies. Immediately after application the increase in superficial temperature, partial preservation of epithelium and subepithelial extracellular matrix coagulation were documented. Later, an increase in epithelial thickness, inflammatory response, fibroblast proliferation, an increase in the amount of collagen, and vascularization were described., Conclusions: Er:YAG laser energy may induce changes in the deeper skin or vaginal wall, without causing unwanted epithelial ablation. Laser energy initiates a process of cell activation, production of extracellular matrix, and tissue remodeling.

Objective: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically., Methods: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing., Results: Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group., Conclusions: In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2020 by The North American Menopause Society.)

Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Therefore, we aimed to develop a functionalized electrospun mesh that promotes tissue ingrowth and provides adequate mechanical strength and compliance during degradation. We describe the in vivo function of a new supramolecular bioactivated polycarbonate (PC) material based on fourfold hydrogen bonding ureidopyrimidinone (UPy) units (UPy-PC). The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Morphometric analysis of the musculofascial content during wound healing showed that cRGD functionalization promotes myogenesis with inhibition of collagen deposition at 14 days. It also prevents muscle atrophy at 90 days and exerts an immunomodulatory effect on infiltrating macrophages at 14 days and foreign body giant cell formation at 14 and 90 days. Additionally, the bioactivated material promotes neovascularization and connective tissue ingrowth. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in the rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. Our results provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. STATEMENT OF SIGNIFICANCE: Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Ureidopyrimidinone-polycarbonate is a elastomeric and biodegradable electrospun mesh, which could mimic physiological compliance. The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. These data provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Although mesh use has significantly improved the outcomes of hernia and pelvic organ prolapse repair, long-term recurrence rates remain unacceptably high. We aim to determine the in vivo degradation and functional outcome of reconstructed abdominal wall defects, using slowly degradable electrospun ureidopyrimidinone moieties incorporated into a polycarbonate backbone (UPy-PC) implant compared to an ultra-lightweight polypropylene (PP) textile mesh with high pore stability. Twenty four New-Zealand rabbits were implanted with UPy-PC or PP to either reinforce a primary fascial defect repair or to cover (referred to as gap bridging) a full-thickness abdominal wall defect. Explants were harvested at 30, 90 and 180 days. The primary outcome measure was uniaxial tensiometry. Secondary outcomes were the recurrence of herniation, morphometry for musculofascial tissue characteristics, inflammatory response and neovascularization. PP explants compromised physiological abdominal wall compliance from 90 days onwards and UPy-PC from 180 days. UPy-PC meshes induced a more vigorous inflammatory response than PP at all time points. We observed progressively more signs of muscle atrophy and intramuscular fatty infiltration in the entire explant area for both mesh types. UPy-PC implants are replaced by a connective tissue stiff enough to prevent abdominal wall herniation in two-thirds of the gap-bridged full-thickness abdominal wall defects. However, in one-third there was sub-clinical herniation. The novel electrospun material did slightly better than the textile PP yet outcomes were still suboptimal. Further research should investigate what drives muscular atrophy, and whether novel polymers would eventually generate a physiological neotissue and can prevent failure and/or avoid collateral damage., Competing Interests: The authors declare no conflict of interest.

Introduction and Hypothesis: Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina., Methods: We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group). We also harvested mid-vaginal and distal vaginal tissue to determine smooth muscle contractility and passive biomechanical properties, for morphometric assessment of the vaginal wall layers, to determine collagen and elastin content, and for immunostaining for α-smooth muscle actin and estrogen receptor-α., Results: There were no regional differences in the nulliparous vagina. One year after the first vaginal delivery, stiffness and contractility of the distal vagina were decreased, whereas the elastin content increased. The mid-vagina of ovariectomized sheep was stiff, and its epithelium was thin and lacked glycogen. HRT decreased the stiffness of the mid-vagina by 45% but had no measurable effect on contractility or elastin content, and increased epithelial thickness and glycogen content. HRT also increased the epithelial thickness and glycogen content of the distal vagina. At this location, there were no changes in morphology or stiffness., Conclusion: In sheep, life events including delivery and ovariectomy affect the biomechanical properties of the vagina in a region-specific way. Vaginal delivery mainly affects the distal region by decreasing stiffness and contractility. HRT can reverse the increase in stiffness of the mid-vagina observed after surgical induction of menopause. These observations are in line with scanty biomechanical measurements in comparable clinical specimens.

Aims: Stress urinary incontinence and pelvic organ prolapse are very common conditions with a proportion of patients requiring implantation of synthetic materials for a durable repair. However increasing numbers of post-surgical complications have been reported related to the use of polypropylene meshes. One hypothesis for the adverse response is poor mechanical matching of the relatively stiff polypropylene mesh particularly as materials in the pelvic floor will need to cope with decades of distension as occurs with increase of intraabdominal pressure on coughing, laughing, or sneezing., Methods: In this study we have undertaken a very simple fatigue testing regime to compare the mechanical abilities of six materials. Four commercial meshes in clinical use and two novel electrospun materials not yet evaluated in the clinic were assessed using a uniaxial tensile test. This was performed on six samples of each dry material and on another six samples of each material after just 3 days of fatigue conditions using a dynamic bioreactor., Results: The four commercial materials showed permanent mechanical deformation after just 3 days of stretching these materials by 25% elongation on a regular dynamic cycle, whereas the two new materials presented more elastic properties without deformation., Conclusions: We suggest that a test as simple as this 3-day fatigue testing is sufficient to distinguish between materials which have already been found to cause complications clinically and newer materials yet to be tested clinically which will hopefully prove more mechanically appropriate for implantation in the pelvic floor., (© 2018 Wiley Periodicals, Inc.)

Background/aims: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan., Methods: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves., Results: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries., Conclusion: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women., (© 2019 S. Karger AG, Basel.)

Purpose: Electrospun meshes mimic the extracellular matrix, which may improve their integration. We aimed to compare polycaprolactone (PCL) modified with ureidopyrimidinone (UPy) electrospun meshes with ultra-lightweight polypropylene (PP; Restorelle) reference textile meshes for in vivo compliance. We chose UPy-PCL because we have shown it does not compromise biomechanical properties of native tissue, and because it potentially can be bioactivated., Methods: We performed ex vivo biomechanical cyclic loading in wet conditions and in vivo overlay of full-thickness abdominal wall defects in rats and rabbits. Animals were sacrificed at 7, 42 and 54 days (rats; n = 6/group) and 30 and 90 days (rabbits; n = 3/group). Outcomes were herniation, mesh degradation and mesh dimensions, explant compliance and histology. High failure rates prompted us to provide additional material strength by increasing fiber diameter and mesh thickness, which was further tested in rabbits as a biomechanically more challenging model., Results: Compliance was tested in animals without herniation. In both species, UPy-PCL-explants were as compliant as native tissue. In rats, PP-explants were stiffer. Contraction was similar in UPy-PCL and PP-explants. However, UPy-PCL-meshes macroscopically degraded from 30 days onwards, coinciding with herniation in up to half of animals. Increased fiber and mesh thickness did not improve outcome. Degradation of UPy-PCL is associated with an abundance of foreign body giant cells until UPy-PCL disappears., Conclusion: Abdominal wall reconstruction with electrospun UPy-PCL meshes failed in 50%. Degradation coincided with a transient vigorous foreign body reaction. Non-failing UPy-PCL-explants were as compliant as native tissue. Despite that, the high failure rate forces us to explore electrospun meshes based on other polymers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Gore-Tex® is a widely used durable patch for repair of congenital diaphragmatic defects yet may result in complications. We compared Gore-Tex with a composite of a radial pore-orientated collagen scaffold (RP-Composite) and clinically used porcine small intestinal submucosa (SIS; Surgisis®) in a rabbit model for diaphragmatic hernia. The growing rabbit mimics the rapid rib cage growth and reherniation rates seen in children. We created and immediately repaired left hemidiaphragmatic defects in 6-week-old rabbits with Gore-Tex, SIS, and an RP-Composite scaffold. An additional group of rabbits had a sham operation. At 90 days, survivors more than doubled in weight. We observed few reherniations or eventrations in Gore-Tex (17%) and RP-Composite (22%) implanted animals. However, SIS failed in all rabbits. Maximum transdiaphragmatic pressure was lower in Gore-Tex (71%) than RP-Composite implanted animals (112%) or sham (134%). Gore-Tex repairs were less compliant than RP-Composite, which behaved as sham diaphragm (p < 0.01). RP-Composite induced less foreign body giant cell reaction than Gore-Tex (p < 0.05) with more collagen deposition (p < 0.001), although there was a tendency for the scaffold to calcify. Unlike Gore-Tex, the compliance of diaphragms reconstructed with RP-Composite scaffolds were comparable with native diaphragm, whereas reherniation rates and transdiaphragmatic pressure measurements were similar., (© 2018 John Wiley & Sons, Ltd.)

Currently cell therapy is considered as an experimental strategy to assist the healing process following simulated vaginal birth injury in rats, boosting the functional and morphologic recovery of pelvic floor muscles and nerves. However, the optimal administration route and dose still need to be determined. Mesangioblasts theoretically have the advantage that they can differentiate in skeletal and smooth muscle. We investigated the fate of mesoangioblasts transduced with luciferase and green fluorescent protein reporter genes (rMABs eGFP/fLUC ) using bioluminescence, immunofluorescence and RT-PCR in rats undergoing simulated birth injury. rMABs eGFP/fLUC were injected locally, intravenously and intra-arterially (common iliacs and aorta). Intra-arterial delivery resulted in the highest amount of rMABs eGFP/fLUC in the pelvic organs region and in a more homogeneous distribution over all relevant pelvic organs. Sham controls showed that the presence of the injury is important for recruitment of intra-arterially injected rMABs eGFP/fLUC . Injection through the aorta or bilaterally in the common iliac arteries resulted in comparable numbers of rMABs eGFP/fLUC in the pelvic organs, yet aortic injection was faster and gave less complications.

Purpose: Electrospun meshes may be considered as substitutes to textile polypropylene implants. We compared the host response and biomechanical properties of the rat abdominal wall following reinforcement with either polycaprolactone (PCL) modified with ureidopyrimidinone-motifs (UPy) or polypropylene mesh., Methods: First we measured the response to cyclic uniaxial load within the physiological range both dry (room temperature) and wet (body temperature). 36 rats underwent primary repair of a full-thickness abdominal wall defect with a polypropylene suture (native tissue repair), or reinforced with either UPy-PCL or ultra-light weight polypropylene mesh (n = 12/group). Sacrifice was at 7 and 42 days. Outcomes were compliance of explants, mesh dimensions, graft related complications and semi-quantitative assessment of inflammatory cell (sub) types, neovascularization and remodeling., Results: Dry UPy-PCL implants are less stiff than polypropylene, both are more compliant in wet conditions. Polypropylene loses stiffness on cyclic loading. Both implant types were well incorporated without clinically obvious degradation or herniation. Exposure rates were similar (n = 2/12) as well as mesh contraction. There was no reinforcement at low loads, while, at higher tension, polypropylene explants were much stiffer than UPy-PCL. The latter was initially weaker yet by 42 days it had a compliance similar to native abdominal wall. There were eventually more foreign body giant cells around UPy-PCL fibers yet the amount of M1 subtype macrophages was higher than in polypropylene explants. There were less neovascularization and collagen deposition., Conclusion: Abdominal wall reconstruction with electrospun UPy-PCL mesh does not compromise physiologic tissue biomechanical properties, yet provokes a vivid inflammatory reaction., (Copyright © 2017. Published by Elsevier Ltd.)

This protocol describes mesh insertion into the rectovaginal septum in sheep using a single vaginal incision technique, with and without the trocar-guided insertion of anchoring arms. Parous sheep underwent the dissection of the rectovaginal septum, followed by the insertion of an implant with or without four anchoring arms, both designed to fit the ovine anatomy. The anchoring arms were put in place using a trocar and an "outside-in" technique. The cranial arms were passed through the obturator, gracilis, and adductor magnus muscles. The caudal arms were fixed near the sacrotuberous ligament, through the coccygeus muscles. This technique allows for the mimicking of surgical procedures performed in women suffering from pelvic organ prolapse. The anatomical spaces and elements are easily identified. The most critical part of the procedure is the insertion of the cranial trocar, which can easily penetrate the peritoneal cavity or the surrounding pelvic organs. This can be avoided by a more extensive retroperitoneal dissection and by guiding the trocar more laterally. This approach is designed only for experimental testing of novel implants in large animal models, as trocar-guided insertion is currently not used clinically.

Pelvic floor soft tissues undergo changes during the pregnancy. However, the degree and nature of this process is not completely characterized. This study investigates the effect of subsequent pregnancy on biomechanical and structural properties of ovine vagina. Vaginal wall from virgin, pregnant (in their third pregnancy) and parous (one year after third vaginal delivery) Swifter sheep (n=5 each) was harvested. Samples for biomechanics and histology, were cut in longitudinal axis (proximal and distal regions). Outcome measurements describing Young's modulus, ultimate stress and elongation were obtained from stress-strain curves. For histology samples were stained with Miller's Elastica staining. Collagen, elastin and muscle cells and myofibroblasts contents were estimated, using image processing techniques. Statistical analyses were performed in order to determine significant differences among experimental groups. Significant regional differences were identified. The proximal vagina was stiffer than distal, irrespective the reproductive status. During the pregnancy proximal vagina become more compliant than in parous (+47.45%) or virgin sheep (+64.35%). This coincided with lower collagen (-15 to -21%), higher elastin (+30 to +60%), and more smooth muscle cells (+17 to +37%). Vaginal tissue from parous ewes was weaker than of virgins, coinciding with lower collagen (-10%), higher elastin (+50%), more smooth muscle cells (+20%). It could be proposed that after pregnancy biomechanical properties of vagina do not recover to those of virgins. Since elastin has a significant influence on the compliance of soft tissues and collagen is the main "actor" regarding strength, histological analysis performed in this study justifies the mechanical behavior observed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background & Objectives: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction., Methods: Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters., Results: Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found., Interpretation & Conclusions: These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease., Competing Interests: None.

Aims: To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 29 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in maternal whole peripheral blood, compared between groups (39 gestational hypertension, 68 preeclampsia, 33 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in patients affected by pregnancy-related complications have been carried out., Results: The expression profile of microRNAs was different between pregnancy-related complications and controls. The down-regulation of miR-100-5p, miR-125b-5p and miR-199a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Moreover, IUGR pregnancies induced down-regulation of miR-17-5p, miR-146a-5p, miR-221-3p and miR-574-3p in maternal circulation. Irrespective of the severity of the disease, preeclampsia was associated with the dysregulation of miR-100-5p and miR-125b-5p and IUGR with dysregulation of miR-199a-5p. Preeclampsia requiring termination of gestation before 34 weeks was associated with down-regulation of miR-146a-5p, miR-199a-5p and miR-221-3p. Weak negative correlation between miR-146a-5p and miR-221-3p expression and the pulsatility index in the umbilical artery was found. Additional microRNAs (miR-103a-3p, miR-126-3p, miR-195-5p and miR-499a-5p) showed a trend to down-regulation in appropriate pregnancy-related complications., Conclusion: Epigenetic changes are induced by pregnancy-related complications in maternal whole peripheral blood., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: To demonstrate that pregnancy-related complications are associated with alterations in cardiovascular and cerebrovascular microRNA expression. Gene expression of 32 microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-33a-5p, miR-92a-3p, miR-100-5p, miR-103a-3p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-208a-3p, miR-210-3p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p) was assessed in placental tissues, compared between groups (35 gestational hypertension, 80 preeclampsia, 35 intrauterine growth restriction and 20 normal pregnancies) and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. Initially, selection and validation of endogenous controls for microRNA expression studies in placental tissues affected by pregnancy-related complications have been carried out., Results: The expression profile of microRNAs was different between pregnancy-related complications and controls. The up-regulation of miR-499a-5p was a common phenomenon shared between gestational hypertension, preeclampsia, and intrauterine growth restriction. Preeclamptic pregnancies delivering after 34 weeks of gestation and IUGR with abnormal values of flow rate in the umbilical artery demonstrated up-regulation of miR-1-3b. Preeclampsia and IUGR requiring termination of gestation before 34 weeks of gestation were associated with down-regulation of miR-26a-5p, miR-103a-3p and miR-145-5p. On the other hand, some of microRNAs (miR-16-5p, miR-100-5p, miR-122-5p, miR-125b-5p, miR-126-3p, miR-143-3p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, and miR-574-3p) were only down-regulated or showed a trend to down-regulation just in intrauterine growth restriction pregnancies requiring the delivery before 34 weeks of gestation., Conclusion: Epigenetic changes induced by pregnancy-related complications in placental tissue may cause later onset of cardiovascular and cerebrovascular diseases in offspring.

To demonstrate that pregnancy-related complications are associated with alterations in placental microRNA expression. Gene expression of 15 C19MC microRNAs (miR-512-5p, miR-515-5p, miR-516-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-519e-5p, miR-520a-5p, miR-520h, miR-524-5p, miR-525, miR-526a, and miR-526b) was assessed in placental tissues, compared between groups (21 gestational hypertension [GH], 63 preeclampsia, 36 fetal growth restriction [FGR], and 42 normal pregnancies), and correlated with the severity of the disease with respect to clinical signs, delivery date, and Doppler ultrasound parameters. The expression profile of microRNAs was different between pregnancy-related complications and controls. The downregulation of 4 of 15 (miR-517-5p, miR-519d, miR-520a-5p, and miR-525), 6 of 15 (miR-517-5p, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, and miR-525), and 11 of 15 (miR-515-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a, miR-519d, miR-520a-5p, miR-520h, miR-524-5p, miR-525, and miR-526a) microRNAs was associated with GH, FGR, and preeclampsia, respectively. Sudden onset of severe preeclampsia requiring immediate termination of gestation and mild forms of preeclampsia (persisting for several weeks) were associated with similar microRNA expression profile (downregulation of miR-517-5p, miR-520a-5p, miR-524-5p, and miR-525). In addition, miR-519a was found to be associated with severe preeclampsia. The longer the pregnancy-related disorder lasted, the more extensive was the downregulation of microRNAs (miR-515-5p, miR-518b, miR-518f-5p, miR-519d, and miR-520h). The downregulation of some C19MC microRNAs is a common phenomenon shared between GH, preeclampsia, and FGR. On the other hand, some of the C19MC microRNAs are only downregulated just in preeclampsia.

The study describes the stress response in the central cotyledon zone of placental tissue and in maternal whole peripheral blood to pregnancy related complications including gestational hypertension (n = 31), preeclampsia w or w/o fetal growth restriction (n = 95), and fetal growth restriction (n = 39) using real-time RT-PCR and genes encoding Hsp27, Hsp60, Hsp70, Hsp90 and HspBP1 proteins. The placental tissue does not respond to pregnancy induced hypertension, fetal growth restriction and short-term severe preeclampsia that requires immediate termination of gestation. Upregulation of Hsp27, Hsp90 and HspBP1 appears just in case of long-term deteriorated conditions (usually in mild preeclampsia, that enable further continuation of gestation, when properly treated). On the other hand, maternal circulation is able to reflect both maternal and fetal pathologic conditions. While pregnancy related complications always induce upregulation of Hsp70 and downregulation of Hsp90 in maternal whole peripheral blood, the increase of Hsp60 mRNA levels occurs entirely in patients with preeclampsia and/or fetal growth restriction. Hsp60, Hsp70 and Hsp90 are dysregulated in maternal circulation irrespective of the severity of the disease (in both mild and severe preeclampsia) and the requirements for the delivery (before and after 34th week of gestation). Nevertheless, the highest Hsp60 mRNA levels may be observed in pregnancies with signs of the centralization of the fetal circulation associated with fetal hypoxia.

Objective: The objective of the study was to evaluate risk assessment for gestational hypertension based on the profile of circulating placental specific C19MC microRNAs in early pregnancy., Study Design: The prospective longitudinal cohort study of women enrolled at first trimester screening at 10 to 13 weeks was carried out (n = 267). Relative quantification of placental specific C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525 and miR-526a) was determined in 28 normal pregnancies and 18 pregnancies which developed gestational hypertension using real-time PCR and a comparative Ct method relative to synthetic C. elegans microRNA (cel-miR-39)., Results: Increased extracellular C19MC microRNA plasmatic levels (miR-516-5p, p<0.001; miR-517*, p = 0.007; miR-520h, p<0.001; miR-518b, p = 0.002) were detected in patients destined to develop gestational hypertension. MiR-520h had the best predictive performance with a PPV of 84.6% at a 7.1% false positive rate. The combination of miR-520h and miR-518b was able to predict 82.6% of women at the same false positive rate. The overall predictive capacity of single miR-518b (73.3% at 14.3% FPR), miR-516-5p (70.6% at 17.9% FPR) and miR-517* (57.9% at 28.6% FPR) biomarkers was lower., Conclusion: The study brought interesting finding that the up-regulation of miR-516-5p, miR-517*, miR-520h and miR-518b is associated with a risk of later development of gestational hypertension. First trimester screening of extracellular miR-520h alone or in combination with miR-518b identified a significant proportion of women with subsequent gestational hypertension.

The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517*, miR-518b, miR-520a*, miR-520h, miR-525, and miR-526a) in patients with established preeclampsia (n = 63), fetal growth restriction (n = 27), and gestational hypertension (n = 23). We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p, P = 0.037, P = 0.009; miR-517*, P = 0.033, P = 0.043; miR-520a*, P = 0.001, P = 0.009; miR-525, P = 0.026, P = 0.01; miR-526a, P = 0.03, P = 0.035) were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517*, miR-520a*, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.