Effects of Low‐Energy Shockwave Therapy on the Erectile Function and Tissue of a Diabetic Rat Model

IntroductionLow‐energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)‐associated erectile dysfunction (ED). However, the underlying mechanism remains unknown.AimThe aim of this study is to investigate whether LESWT can ameliorate DM‐associated ED in a rat model and examine the associated changes in the erectile tissues.MethodsNewborn male rats were intraperitoneally injected with 5‐ethynyl‐2‐deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, eight of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group), whereas another eight rats were subject to shockwave (SW) treatment (DM+SW group). Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm² and frequency of 120/minute. This procedure was repeated three times a week for 2 weeks. Another 2 weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology.Main Outcome MeasuresErectile function was measured by ICP. Neuronal nitric oxide synthase (nNOS)‐positive nerves and the endothelium were examined by immunofluorescence staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively.ResultsSTZ treatment caused a significant decrease in erectile function and in the number of nNOS‐positive nerves and in endothelial and smooth muscle contents. These DM‐associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU‐positive cells) were significantly more numerous in DM+SW than in DM rats.ConclusionLESWT can partially ameliorate DM‐associated ED by promoting regeneration of nNOS‐positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by recruitment of endogenous MSCs. Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, and Lin C‐S. Effects of low‐energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med 2013;10:738–746.     

A “Boots on the Ground” Perspective of Caring for the Women and Children in Afghanistan

In 1972 Margarete V. Silberberg wrote about her nursing experience when caring for women at a Kabul, Afghanistan, hospital. Based on my experience during a recent deployment to Afghanistan, I describe providing health care to Afghan women and children as a military Women's Health Nurse Practitioner. Delivering health care presented the threat of physical harm for the health care team and those who received the care. Afghan women and children continue to experience significant cultural, religious, and social circumstances that limit their education, personal development, protection from abuse, and access to health care.     

What Is the Impact of the Internet on Decision‐Making in Pregnancy? A Global Study

Abstract: Background: Women need access to evidence‐based information to make informed choices in pregnancy. A search for health information is one of the major reasons that people worldwide access the Internet. Recent years have witnessed an increase in Internet usage by women seeking pregnancy‐related information. The aim of this study was to build on previous quantitative studies to explore women’s experiences and perceptions of using the Internet for retrieving pregnancy‐related information, and its influence on their decision‐making processes. Methods: This global study drew on the interpretive qualitative traditions together with a theoretical model on information seeking, adapted to understand Internet use in pregnancy and its role in relation to decision‐making. Thirteen asynchronous online focus groups across five countries were conducted with 92 women who had accessed the Internet for pregnancy‐related information over a 3‐month period. Data were readily transferred and analyzed deductively. Results: The overall analysis indicates that the Internet is having a visible impact on women’s decision making in regards to all aspects of their pregnancy. The key emergent theme was the great need for information. Four broad themes also emerged: “validate information,”“empowerment,”“share experiences,” and “assisted decision‐making.” Women also reported how the Internet provided support, its negative and positive aspects, and as a source of accurate, timely information. Conclusion: Health professionals have a responsibility to acknowledge that women access the Internet for support and pregnancy‐related information to assist in their decision‐making. Health professionals must learn to work in partnership with women to guide them toward evidence‐based websites and be prepared to discuss the ensuing information. (BIRTH 38:4 December 2011)     

Therapeutic Potential of Adipose‐Derived Stem Cells‐Based Micro‐Tissues in a Rat Model of Postprostatectomy Erectile Dysfunction

IntroductionStem cells (SCs) show significant benefits in the treatment of postprostatectomy erectile dysfunction (ED). However, the low retention rate of the traditional single‐cell strategy at the injection sites limits its therapeutic potential.AimThis study aims to investigate the feasibility and mechanism of adipose‐derived stem cells (ADSCs)‐based micro‐tissues (MTs) in the treatment of ED in a rat model of bilateral cavernous nerves (CNs) injury.MethodsADSCs labeled with 5‐ethynyl‐2‐deoxyuridine (EdU) were used to generate MTs with hanging drop method. 10 Sprague‐Dawley (SD) rats underwent sham surgery and intracavernous (IC) injection of phosphate buffer solution (PBS) (the sham group). Another 70 rats underwent bilateral CN crush and were then treated with PBS (n = 10, the crush group), dissociated ADSCs (n = 30, the ADSCs group), and MTs (n = 30, the MTs group), respectively. At day 1, 3, 7, 14 (n = 5), and 28 (n = 10) postsurgery, specimens were harvested for histology. At day 28, 10 rats in each group were examined for erectile function before tissue harvest.Main Outcome MeasuresLight microscopy of the dynamic aggregation of the MT, immunohistologic examination of the MTs, the retention and distribution of EdU + ADSCs in the corpus cavernosum (CC), and the penis histological analyses of collagen content, Western blot of functional proteins in MTs, intracavernous pressure recording on CN electrostimulation.ResultsThree‐day‐old MTs became stable and expressed nerve growth factor, vascular endothelial growth factor, C‐X‐C chemokine receptor type 4, Wnt5a, and collagen IV. More EdU + ADSCs retained in the CC in the MTs group than that in the ADSCs group. IC injection of MTs resulted in significant restoration of the erectile function and histopathological changes compared with the ADSCs group.ConclusionIC‐injected MTs resulted in a better restoration of erectile function than traditional single‐cell strategy. The underlying mechanisms of recovery appear to involve enhanced cellular retention in the penis and upregulation of some paracrine factors. Xu Y, Guan R, Lei H, Li H, Wang L, Gao Z, Song W, and Xin Z. Therapeutic potential of adipose‐derived stem cells‐based micro‐tissues in a rat model of postprostatectomy erectile dysfunction. J Sex Med 2014;11:2439–2448.     

Sexual Function in the Late Postmenopause: A Decade of Follow‐Up in a Population‐Based Cohort of Australian Women

IntroductionThere is a paucity of longitudinal studies assessing sexual function of women in the late postmenopause.AimThis study aims to describe sexual function of women in the late postmenopause and to investigate change from early postmenopause.MethodsCross‐sectional analysis of 2012/13 and longitudinal analysis from 2002/04 of the population based, Australian cohort of the Women's Healthy Ageing Project, applying validated instruments: Short Personal Experience Questionnaire (SPEQ), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale, Geriatric Depression Scale, and California Verbal Learning Test.Main Outcome MeasuresSexual activity, SPEQ, and FSDS.ResultsTwo hundred thirty women responded (follow‐up rate 53%), mean age was 70 years (range 64–77), 49.8% were sexually active. FSDS scores showed more distress for sexually active women (8.3 vs. 3.2, P < 0.001). For 23 (23%) sexually active and for five (7%) inactive women, the diagnosis of female sexual dysfunction could be made. After adjustment, available partner (odds ratio [OR] 4.31, P < 0.001), no history of depression (OR 0.49, P = 0.036), moderate compared with no alcohol consumption (OR 2.43, P = 0.019), and better cognitive function score (OR1.09, P = 0.050) were significantly predictive for sexual activity. Compared with early postmenopause, 18% more women had ceased sexual activity. For women maintaining their sexual activity through to late postmenopause (n = 82), SPEQ and FSDS scores had not changed significantly, but frequency of sexual activity had decreased (P = 0.003) and partner difficulties had increased (P = 0.043). [Correction added on 10 July 2014, after first online publication: Mean age of respondents was added.]ConclusionsIn late postmenopause, half of the women were sexually active. Most important predictors were partner availability and no history of depression. However, being sexually active or having a partner were associated with higher levels of sexual distress. Compared with early postmenopause, sexual function scores had declined overall but were stable for women maintaining sexual activity. Further research into causes of sexual distress and reasons for sexual inactivity at this reproductive stage is warranted. Lonnèe‐Hoffmann RAM, Dennerstein L, Lehert P, and Szoeke C. Sexual function in the late postmenopause: A decade of follow‐up in a population‐based cohort of Australian women. J Sex Med 2014;11:2029–2038.     

Role of Leptin in Pregnancy—A Review

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05).We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg.Resistin is a novel adipocyte–derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.     

Analysis of the S810L Point Mutation of the Mineralocorticoid Receptor in Patients with Pregnancy‐Induced Hypertension

Objective. A missense mutation at codon 810 (Ser → Leu) of the mineralocorticoid receptor was recently observed in a family with early manifestation of hypertension. Our objective was to determine if this mineralocorticoid receptor alterations is prevalent in patients with pregnancy‐induced hypertension. Methods. Thirty‐eight women with hypertension during pregnancy were tested for the mineralocorticoid receptor gene mutation. DNA was extracted out of blood leucocytes. PCR and automated DNA sequencing were used to analyze exon 6 for the S810L missense mutation. Anamnestical data concerning cardiovascular risk factors and family history were evaluated with a questionnaire. Pregnancy course and outcome were documented in all cases. Results. In 33 patients with pregnancy‐induced hypertension and in five patients with exacerbation of preexisting hypertension in pregnancy no point mutations were found at codon 810 in exon 6. Conclusions. Our data suggest that the S810L missense mutation of the mineralocorticoid receptor does not play a major role in the etiology of pregnancy‐induced hypertension in a German /Turkish population.     

Effects of Intravenous Injection of Adipose‐Derived Stem Cells in a Rat Model of Radiation Therapy‐Induced Erectile Dysfunction

IntroductionRadiation therapy (RT) for prostate cancer is frequently associated with posttreatment erectile dysfunction (ED).AimTo investigate whether injection of adipose‐derived stem cells (ADSCs) can ameliorate RT‐associated ED.MethodsThirty male rats were divided into three groups. The control + phosphate‐buffered saline (PBS) group received tail‐vein injection of PBS. The radiation + PBS group received radiation over the prostate and tail‐vein injection of PBS. The radiation + ADSC group received radiation over the prostate and tail‐vein injection of ADSCs, which were labeled with 5‐ethynyl‐2‐deoxyuridine (EdU). Seventeen weeks later, erectile function was evaluated by intracavernous pressure (ICP) in response to electrostimulation of cavernous nerves (CNs). Penile tissue and major pelvic ganglia (MPG) were examined by immunofluorescence (IF) and EdU staining.Main Outcome MeasuresErectile function was measured by ICP. Protein expression was examined by IF, followed by image analysis and quantification.ResultsRadiation over the prostate caused a significant decrease in erectile function and in the expression of neuronal nitric oxide synthase (nNOS) in penis and MPG. Cavernous smooth muscle (CSM) but not endothelial content was also reduced. Injection of ADSCs significantly restored erectile function, nNOS expression, and CSM content in the irradiated rats. EdU‐positive cells were visible in MPG.ConclusionsRadiation appears to cause ED via CN injury. ADSC injection can restore erectile function via CN regeneration. Qiu X, Villalta J, Ferretti L, Fandel TM, Albersen M, Lin G, Dai Y, Lue TF, and Lin C‐S. Effects of intravenous injection of adipose‐derived stem cells in a rat model of radiation therapy‐induced erectile dysfunction. J Sex Med 2012;9:1851–1858.     

Effects of Women’s Weight Changes on Adverse Outcomes in a Second Pregnancy

ObjectiveTo estimate the effects of women’s weight changes in four sequential perinatal periods across first and second pregnancies (pregravid, first gestation, interpregnancy, second gestation) on adverse maternal and neonatal outcomes in the second pregnancy while accounting for interdependencies in weight across the four periods (Aim 1) and to test the influence of the sequential path of weight changes through the four perinatal periods of risk on maternal and neonatal outcomes in the second pregnancy (Aim 2).DesignSecondary data analysis.SettingThirty-one Wisconsin hospitals.SampleWomen with 24,795 linked records from first and second births from 2006 through 2013.MethodsWe used a fully recursive system of linear and logistic regression equations to examine the relationships among weight changes in the four perinatal periods with maternal (gestational diabetes mellitus, gestational hypertension, cesarean birth) and neonatal (macrosomia, small for gestational age, large for gestational age, low birth weight, congenital anomalies, and perinatal death) adverse outcomes in the second pregnancy.ResultsPregravid weight was weakly and inconsistently associated with weight changes in subsequent periods. Each 5-kg incremental weight change in the first pregnancy, interpregnancy, and second pregnancy contributed to a 0.75- to 5-kg weight change in subsequent periods, 9% to 25% change in risk for adverse maternal outcomes, and 8% to 47% change in risk for adverse neonatal outcomes in the second pregnancy. Fluctuations in weight across pregnancies and associations with outcomes were strongest among normal-weight and overweight women.ConclusionWeight changes across two pregnancies affected maternal and neonatal outcomes in the second pregnancy in all body mass index categories; the larger weight fluctuations observed in normal and overweight women were associated with greater risk of adverse outcomes. Attention to pregnancy weight during and between pregnancies is important for targeted weight counseling to reduce risks in subsequent pregnancies.     

Ectopic Pregnancy in the Era of Medical Abortion: Are We Ready for It? Spectrum of Sonographic Findings and Our Experience in a Tertiary Care Service Hospital of India

Aim

The aim of this study was to share our experience of clinical presentation and ultrasonographic findings in cases of ectopic pregnancy especially in the context of usage of unsupervised medical abortifacients.

Settings and Design

This is prospective study conducted over a period of 1 year extending from August 01, 2009 to July 31, 2010 in a tertiary care Armed Forces Hospital of India.

Materials and Methods

Clinically and or sonologically suspected cases of ectopic pregnancy formed the study group. Detailed clinical, menstrual, and treatment history was obtained for each patient. Ultrasonography (USG) was done with multifrequency convex (2.5–6 MHz) followed by transvaginal (6–10 MHz) probes. Operative findings were noted and recorded in each case.

Results

In the study period, a total of 1958 pregnant patients were admitted and treated, which included 1690 deliveries and 268 abortions. Based on USG findings, 16 cases (0.8 %) of ectopic pregnancy were diagnosed. While four patients were treated medically (with methotrexate), 12 cases underwent surgery. Out of 16 cases, 10 cases were suspected clinically as ectopic pregnancy. Features suggestive of menorrhagia, threatened abortion, and pelvic inflammatory disease were present in five, three, and three cases, respectively. History of intake of medical abortifacients (MA) (mifepristone followed by misoprostol) was present in 07 (43.75 %) cases. On USG, commonest abnormality was a complex adnexal mass seen in 12 (75 %) cases. Gestational sac with definite embryo within and surrounding echogenic rim was seen in five cases. Live ectopic pregnancy was diagnosed in two (12.5 %) cases. Endometrial thickness was less than 10 mm in all cases who had taken MA. Pseudo gestation sac was seen in 02 (12.5 %) cases. Significant hemoperitoneum was present in 10 out of 12 cases operated. Organized hematoma in pelvis masking the presence of adnexal mass was noted in three cases.

Conclusion

Over-the-counter availability, failure to strictly follow the guidelines, unsupervised usage of MA along with atypical clinical history have increased diagnostic dilemma in ectopic pregnancy. Sonographic findings are frequently atypical in such cases. Ectopic pregnancy may remain under-diagnosed with potentially serious consequences in patients who have taken MA without prior confirmation of intrauterine gestation.     

Effect of Intracavernous Administration of Angiopoietin‐4 on Erectile Function in the Streptozotocin‐Induced Diabetic Mouse

IntroductionErectile dysfunction (ED) is a highly prevalent complication of diabetes, and the severity of endothelial dysfunction is one of the most important factors in reduced responsiveness to oral phosphodiesterase type 5 inhibitors.AimTo study the effects of human angiopoietin‐4 (Ang‐4) protein on erectile function in diabetic mice.MethodsDiabetes was induced by intraperitoneal injection of streptozotocin into 8‐week‐old C57BL/6J male mice. At 8 weeks after the induction of diabetes, the animals were divided into four groups: control nondiabetic mice and diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (days ?3 and 0), a single intracavernous injection of Ang‐4 protein (day 0), or two successive intracavernous injections of Ang‐4 protein (days ?3 and 0).Main Outcome MeasuresOne week after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested and stained with hydroethidine or antibodies to Ang‐4, platelet/endothelial cell adhesion molecule‐1, and phosphorylated endothelial nitric oxide synthase (eNOS). We also determined the differential expression of Ang‐4 in cavernous tissue in the control and diabetic mice. The effect of Ang‐4 protein on the phosphorylation of Tie‐2, Akt, and eNOS was determined in human umbilical vein endothelial cells (HUVECs) by Western blot.ResultsThe cavernous expression of Ang‐4 was downregulated in diabetic mice; Ang‐4 was mainly expressed in endothelial cells. Local delivery of Ang‐4 protein significantly increased cavernous endothelial content, induced eNOS phosphorylation, and decreased the generation of superoxide anion and apoptosis in diabetic mice. Ang‐4 protein strongly increased the phosphorylation of Tie‐2, Akt, and eNOS in HUVECs. Repeated intracavernous injections of Ang‐4 induced significant restoration of erectile function in diabetic mice (87% of control values), whereas a single intracavernous injection of Ang‐4 protein elicited modest improvement.ConclusionsCavernous endothelial regeneration by use of Ang‐4 protein may have potential for the treatment of vascular disease‐induced ED, such as diabetic ED. Kwon M‐H, Ryu J‐K, Kim WJ, Jin H‐R, Song K‐M, Kwon K‐D, Batbold D, Yin GN, Koh GY, and Suh J‐K. Effect of intracavernous administration of angiopoietin‐4 on erectile function in the streptozotocin‐induced diabetic mouse. J Sex Med 2013;10:2912–2927.     

Therapeutic Effect of Adipose‐Derived Stem Cells and BDNF‐immobilized PLGA Membrane in a Rat Model of Cavernous Nerve Injury

IntroductionCavernous nerve injury is the main reason for post‐prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED.AimTo evaluate the therapeutic efficacy of adipose‐derived stem cells (ADSCs) and brain‐derived neurotrophic factor (BDNF) immobilized Poly‐Lactic‐Co‐Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post‐prostatectomy ED.MethodsRats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF‐membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF‐membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled‐released for a period of 4 weeks in a BDNF/PLGA porous membrane system.Main Outcome MeasuresFour weeks after the operation, erectile function was assessed by detecting the ratio of intra‐cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho‐endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively.ResultsIn the ADSC/BDNF‐membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF‐membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho‐eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups.ConclusionsADSCs with BDNF‐membrane on the cavernous nerve can improve erectile function in a rat model of post‐prostatectomy ED, which may be used as a novel therapy for post‐prostatectomy ED. Piao S, Kim IG, Lee JY, Hong SH, Kim SW, Hwang T‐K., Heang S, Lee JH, Ra JC, and Lee JY. Therapeutic effect of adipose‐derived stem cells and BDNF‐immobilized PLGA membrane in a rat model of cavernous nerve injury. J Sex Med 2012;9:1968–1979.     

Tadalafil Effect on Metabolic Syndrome‐Associated Bladder Alterations: An Experimental Study in a Rabbit Model

IntroductionMetabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) are often associated. Bladder detrusor hyper‐contractility—a major LUTS determinant—is characterized by increased Ras homolog gene family, member A/Rho‐associated protein kinase (RhoA/ROCK) signaling, which is often upregulated in MetS.AimThis study investigated the effects of tadalafil dosing on RhoA/ROCK signaling in bladder, in a rabbit model of high‐fat diet (HFD)‐induced MetS.MethodsAdult male rabbits feeding a HFD for 12 weeks. A subset of HFD animals was treated with tadalafil (2 mg/kg/day, 1 week: the last of the 12 weeks) and compared with HFD and control (feeding a regular diet) rabbits.Main Outcome MeasuresIn vitro contractility studies to evaluate the relaxant effect of the selective ROCK inhibitor, Y‐27632, in carbachol precontracted bladder strips. Evaluation of RhoA activation by its membrane translocation. Immunohistochemistry for ROCK expression has been performed to evaluate ROCK expression in bladder from the different experimental groups. mRNA expression of inflammation, pro‐fibrotic markers by quantitative RT‐PCR has been performed to evaluate the effect of tadalafil on MetS‐induced inflammation and fibrosis within the bladder. The in vitro effect of tadalafil on RhoA/ROCK signaling in bladder smooth muscle cells was evaluated by using chemotaxis assay.ResultsBladder strips from HFD rabbits showed hyper‐responsiveness to Y‐27632, indicating RhoA/ROCK overactivity in HFD bladder compared with matched controls. Accordingly, the fraction of activated (translocated to the membrane) RhoA as well as ROCK expression are increased in HFD bladder. Tadalafil dosing normalized HFD‐induced bladder hypersensitivity to Y‐27632, by reducing RhoA membrane translocation and ROCK overexpression. Tadalafil dosing reduced mRNA expression of inflammatory, pro‐fibrotic, and hypoxia markers. A direct inhibitory effect of tadalafil on RhoA/ROCK signaling in bladder smooth muscle cell was demonstrated by using chemotaxis assay. Pre‐treatment with tadalafil inhibited both basal and PDGF‐induced migration of bladder smooth muscle cells.ConclusionsTadalafil dosing reduced RhoA/ROCK signaling and smooth muscle overactivity in an animal model of MetS‐associated bladder alterations. Our findings suggest a novel mechanism of action of tadalafil in alleviating LUTS in MetS patients. Vignozzi L, Filippi S, Comeglio P, Cellai I, Morelli A, Maneschi E, Sarchielli E, Gacci M, Carini M, Vannelli GB, and Maggi M. Tadalafil effect on metabolic syndrome‐associated bladder alterations: An experimental study in a rabbit model. J Sex Med 2014;11:1159–1172.     

TNF-α in Pregnancy Loss and Embryo Maldevelopment: A Mediator of Detrimental Stimuli or a Protector of the Fetoplacental Unit?

Purpose : Tumor necrosis factor alpha (TNF-), a multifunctional cytokine, has been identified in the ovary, oviduct, uterus, and placenta, and is expressed in embryonic tissues. For many years TNF- was mainly considered to be a cytokine involved in triggering immunological pregnancy loss and as a mediator of various embryopathic stresses. However, data collected during the last decade has characterized TNF- not only as a powerful activator of apoptotic, but also antiapoptotic signaling cascades, as well as revealed its regulatory role in cell proliferation. This review summarizes and conceptualizes the studies addressing TNF--activated intracellular signaling and the possible functional role of TNF- in embryonic development. Methods : Studies addressing the role of TNF- in intercellular signaling, in vivo studies addressing the functional role TNF- in spontaneous and induced pregnancy loss, and studies addressing the role of TNF- in fetal malformations were reviewed. Comparative studies in TNF- knockout and TNF- positive mice were performed to evaluate embryonic death, structural anomalies in fetuses, the degree of apoptosis and cell proliferation, and the activity of molecules such as caspases 3 and 8, the NF-B, (RelA), IB in some target embryonic organs shortly after exposure to embryopathic stresses. Results : It is proposed that the possible essential function of TNF- may be to prevent the birth of offspring with structural anomalies. Conclusions : TNF- will boost death signaling to kill the embryo if initial events (damages) triggered by detrimental stimuli may culminate in structural anomalies, and stimulate protective mechanisms if the repair of these damages may prevent maldevelopment.     

Effects of Methylene Blue on Ovarian Torsion−Detorsion Injury in a Rat Model

Study Objectives:Methylene blue (MB) is an antioxidant that ameliorates ischemia-reperfusion injury in several tissues. We analyzed the effects of MB as an inhibitor of torsion–detorsion injury in rat ovaries.MethodsRats were randomly divided into 5 groups. Group 1 was the sham group, in which only laparotomy was performed. Group 2 was the torsion group, with 3 hours of ischemia. Group 3 was the torsion + MB group, with 3 hours of ischemia after MB administration. Group 4 was the torsion–detorsion group, with 3 hours of ischemia and reperfusion. Finally, group 5 was the torsion–detorsion + MB group, with 3 hours of ischemia and MB administration before detorsion/reperfusion. Ovary injuries were histopathologically scored. Malondialdehyde (MDA) and total protein levels in ovarian tissues were determined, and long pentraxin-3 (PTX3) levels were measured in ovarian tissue using an enzyme-linked immunosorbent assay.ResultsIn comparing group 4 with group 5 and group 2 with 3, histopathological parameters reflecting injury were significantly increased in groups 4 and 2. Group 3 generated increased MDA levels when compared with group 2 (P < .05). However, there was no significant difference between groups 2 and 3 in terms of plasma PTX3 levels. MDA and PTX3 levels decreased in group 5 in comparison with group 4 for MDA (P < .000) and PTX3 levels (P < .01).ConclusionsMB alleviated ischemia-reperfusion ovary injury in our experimental model.