Unexpected Role of Physiological Estrogen in Acute Stress-Induced Memory Deficits.

Stress may promote emotional and cognitive disturbances, which differ by sex. Adverse outcomes, including memory disturbances, are typically observed following chronic stress, but are now being recognized also after short events, including mass shootings, assault, or natural disasters, events that consist of concurrent multiple acute stresses (MAS). Prior work has established profound and enduring effects of MAS on memory in males. Here we examined the effects of MAS on female mice and probed the role of hormonal fluctuations during the estrous cycle on MAS-induced memory problems and the underlying brain network and cellular mechanisms. Female mice were impacted by MAS in an estrous cycle-dependent manner: MAS impaired hippocampus-dependent spatial memory in early-proestrous mice, characterized by high levels of estradiol, whereas memory of mice stressed during estrus (low estradiol) was spared. As spatial memory requires an intact dorsal hippocampal CA1, we examined synaptic integrity in mice stressed at different cycle phases and found a congruence of dendritic spine density and spatial memory deficits, with reduced spine density only in mice stressed during high estradiol cycle phases. Assessing MAS-induced activation of brain networks interconnected with hippocampus, we identified differential estrous cycle-dependent activation of memory- and stress-related regions, including the amygdala. Network analyses of the cross-correlation of fos expression among these regions uncovered functional connectivity that differentiated impaired mice from those not impaired by MAS. In conclusion, the estrous cycle modulates the impact of MAS on spatial memory, and fluctuating physiological levels of sex hormones may contribute to this effect.SIGNIFICANCE STATEMENT: Effects of stress on brain functions, including memory, are profound and sex-dependent. Acute stressors occurring simultaneously result in spatial memory impairments in males, but effects on females are unknown. Here we identified estrous cycle-dependent effects of such stresses on memory in females. Surprisingly, females with higher physiological estradiol experienced stress-induced memory impairment and a loss of underlying synapses. Memory- and stress-responsive brain regions interconnected with hippocampus were differentially activated across high and low estradiol mice, and predicted memory impairment. Thus, at functional, network, and cellular levels, physiological estradiol influences the effects of stress on memory in females, providing insight into mechanisms of prominent sex differences in stress-related memory disorders, such as post-traumatic stress disorder.

Endometritis decreases the population of uterine neurons in the paracervical ganglion and changes the expression of sympathetic neurotransmitters in sexually mature gilts.

BACKGROUND: The focus of the study was to examine the impact of the inflamed uterus on the population of the paracervical ganglion (PCG) uterus-innervating perikarya and their chemical coding. Fast Blue retrograde tracer was injected into the wall of uterine horns on the 17th day of the first studied estrous cycle. After 28 days, either Escherichia coli suspension or saline was applied to the horns of the uterus, whereas the control group received laparotomy only. Eight days after the above-mentioned procedures, uterine cervices with PCG were collected. Both macroscopic and histopathologic examinations confirmed severe acute endometritis in the Escherichia coli-injected uteri. The double immunofluorescence method was used to analyze changes in the PCG populations coded with dopamine-ß-hydroxylase (DßH) and/or neuropeptide Y (NPY), somatostatin (SOM), vasoactive intestinal polypeptide (VIP) and neuronal isoform of nitric oxide synthase (nNOS). RESULTS: The use of Escherichia coli lowered the total number of Fast Blue-positive neurons. Moreover, an increase in DßH+/VIP+, DßH+/NPY+, DßH+/SOM + and DßH+/nNOS + expressing perikarya was noted. A rise in non-noradrenergic VIP-, SOM- and nNOS-immunopositive populations was also recorded, as well as a drop in DßH-positive neurotransmitter-negative neurons. CONCLUSIONS: To sum up, inflammation of the uterus has an impact on the neurochemical properties of the uterine perikarya in PCG, possibly affecting the functions of the organ.

Nerve-sparing in Gynecology.

OBJECTIVE: To demonstrate identification and dissection of the pelvic autonomic nerves in gynecologic surgery. DESIGN: Identification on the right and left pelvic pelvises, dissection and preservation of the inferior hypogastric plexus in deep endometriosis, and dissection and preservation of the pelvic autonomic nerves in radical hysterectomy. SETTING: Academic center. INTERVENTIONS: Robotic excision of the pelvic peritoneum, excision of deep endometriosis in the uterosacral ligaments, and radical hysterectomy. CONCLUSION: Pelvic autonomic nerves are easy to identify with the magnification provided with an endoscopic camera. They should be dissected and preserved whenever possible because of their important function.

Neuropilin-1 receptor in the rapid and selective estrogen-induced neurovascular remodeling of rat uterus.

Sympathetic nerves innervate most organs and regulate organ blood flow. Specifically, in the uterus, estradiol (E2) elicits rapid degeneration of sympathetic axons and stimulates the growth of blood vessels. Both physiological remodeling processes, critical for reproduction, have been extensively studied but as independent events and are still not fully understood. Here, we examine the neuropilin-1 (NRP1), a shared receptor for axon guidance and angiogenic factors. Systemic estradiol or vehicle were chronically injected to prepubertal rats and uterine and sympathetic chain sections immunostained for NRP1. Uterine semaphorin-3A mRNA was evaluated by in situ hybridization. Control sympathetic uterine-projecting neurons (1-month-old) expressed NRP1 in their somas but not in their intrauterine terminal axons. Estradiol did not affect NRP1 in the distal ganglia. However, at the entrance of the organ, some sympathetic NRP1-positive nerves were recognized. Vascular NRP1 was confined to intrauterine small-diameter vessels in both hormonal conditions. Although the overall pattern of NRP1-IR was not affected by E2 treatment, a subpopulation of infiltrated eosinophil leukocytes showed immunoreactivity for NRP1. Sema3A transcripts were detected in this cellular type as well. No NRP1-immunoreactive axons nor infiltrated eosinophils were visualized in other estrogenized pelvic organs. Together, these data suggest the involvement of NRP1/Sema3A signaling in the selective E2-induced uterine neurovascular remodeling. Our data support a model whereby NRP1 could coordinate E2-induced uterine neurovascular remodeling, acting as a positive regulator of growth when expressed in vessels and as a negative regulator of growth when expressed on axons.

Laparoscopic surgery for endometriosis.

BACKGROUND: Endometriosis is associated with pain and infertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. OBJECTIVES: To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis. SEARCH METHODS: This review has drawn on the search strategy developed by the Cochrane Gynaecology and Fertility Group including searching the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, reference lists for relevant trials, and trial registries from inception to April 2020. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that compared the effectiveness and safety of laparoscopic surgery with any other laparoscopic or robotic intervention, holistic or medical treatment, or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Two review authors independently performed selection of studies, assessment of trial quality and extraction of relevant data with disagreements resolved by a third review author. We collected data for the core outcome set for endometriosis. Primary outcomes included overall pain and live birth. We evaluated the quality of evidence using GRADE methods. MAIN RESULTS: We included 14 RCTs. The studies randomised 1563 women with endometriosis. Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only. Two RCTs compared laparoscopic excision with diagnostic laparoscopy only. One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension. Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only. One RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin-releasing hormone (GnRH) analogues. Two RCTs compared laparoscopic ablation with laparoscopic excision. One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy. One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep endometriosis infiltrating the rectum. Common limitations in the primary studies included lack of clearly described blinding, failure to fully describe methods of randomisation and allocation concealment, and poor reporting of outcome data. Laparoscopic treatment versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic treatment on overall pain scores compared to diagnostic laparoscopy only at six months (mean difference (MD) 0.90, 95% confidence interval (CI) 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence), where a positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain). No studies looked at live birth. We are uncertain of the effect of laparoscopic treatment on quality of life compared to diagnostic laparoscopy only: EuroQol-5D index summary at six months (MD 0.03, 95% CI -0.12 to 0.18; 1 RCT, 39 participants; low quality evidence), 12-item Short Form (SF-12) mental health component (MD 2.30, 95% CI -4.50 to 9.10; 1 RCT, 39 participants; low quality evidence) and SF-12 physical health component (MD 2.70, 95% CI -2.90 to 8.30; 1 RCT, 39 participants; low quality evidence). Laparoscopic treatment probably improves viable intrauterine pregnancy rate compared to diagnostic laparoscopy only (odds ratio (OR) 1.89, 95% CI 1.25 to 2.86; 3 RCTs, 528 participants; I2 = 0%; moderate quality evidence). We are uncertain of the effect of laparoscopic treatment compared to diagnostic laparoscopy only on ectopic pregnancy (MD 1.18, 95% CI 0.10 to 13.48; 1 RCT, 100 participants; low quality evidence) and miscarriage (MD 0.94, 95% CI 0.35 to 2.54; 2 RCTs, 112 participants; low quality evidence). There was limited reporting of adverse events. No conversions to laparotomy were reported in both groups (1 RCT, 341 participants). Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy We are uncertain of the effect of laparoscopic ablation and uterine nerve transection on adverse events (more specifically vascular injury) compared to diagnostic laparoscopy only (OR 0.33, 95% CI 0.01 to 8.32; 1 RCT, 141 participants; low quality evidence). No studies looked at overall pain scores (at six and 12 months), live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. Laparoscopic ablation versus laparoscopic excision There was insufficient evidence to determine whether there was a difference in overall pain, measured at 12 months, for laparoscopic ablation compared with laparoscopic excision (MD 0.00, 95% CI -1.22 to 1.22; 1 RCT, 103 participants; very low quality evidence). No studies looked at overall pain scores at six months, live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy, miscarriage and adverse events. Helium thermal coagulator versus electrodiathermy We are uncertain whether helium thermal coagulator compared to electrodiathermy improves quality of life using the 30-item Endometriosis Health Profile (EHP-30) at nine months, when considering the components: pain (MD 6.68, 95% CI -3.07 to 16.43; 1 RCT, 119 participants; very low quality evidence), control and powerlessness (MD 4.79, 95% CI -6.92 to 16.50; 1 RCT, 119 participants; very low quality evidence), emotional well-being (MD 6.17, 95% CI -3.95 to 16.29; 1 RCT, 119 participants; very low quality evidence) and social support (MD 5.62, 95% CI -6.21 to 17.45; 1 RCT, 119 participants; very low quality evidence). Adverse events were not estimable. No studies looked at overall pain scores (at six and 12 months), live birth, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage. AUTHORS' CONCLUSIONS: Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. No data were reported on live birth. There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only. No studies were found that looked at live birth for any of the comparisons. Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Three-Dimensional Peripheral Bloodstream Model of the Uterus for Laparoscopic Radical Hysterectomy.

Trainees require extensive experience to perform radical hysterectomy. Before starting training during an actual operation, trainees should be familiar with the pelvic anatomy and should simulate surgical procedures. Many simulators are available for virtual reality training of laparoscopic operations, but they are very expensive. The materials required to construct our model included sponges and colored wires sold in home improvement stores that allowed for superior cost effectiveness. The model represented almost all peripheral vessels and nerves around the uterus, including the minor vessels. Attaching and detaching the vessels was easy, facilitating reconstruction of the dissected vessels. The wires were easy to bend, ensuring high operability. This model allows for the simulation of laparoscopic radical hysterectomy in a dry box. Our model was superior to a 2-dimensional picture for the memorization of branching and positional relationships of the blood vessels. Comparison of our model with actual operative videos showed that the dry box provided an identical surgical view of an actual laparoscopic radical hysterectomy. We developed a peripheral bloodstream model of the uterus for repeated simulation of laparoscopic radical hysterectomy with an actual surgical view using a dry box.

Laparoscopic Nerve-Sparing Radical Hysterectomy vs Laparoscopic Radical Hysterectomy in Cervical Cancer: A Systematic Review and Meta-Analysis of Clinical Efficacy and Bladder Dysfunction.

It is widely accepted that nerve-sparing radical hysterectomy is associated with less postoperative morbidity compared with radical hysterectomy, whereas clinical safety is similar in the 2 procedures. However, there is insufficient evidence to compare these procedures performed via a laparoscopic approach. We performed a systematic review and meta-analysis of studies to compare the clinical efficacy and the rate of bladder dysfunction, including urodynamic assessment, in laparoscopic nerve-sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH). Thirty articles including a total of 2743 participants were analyzed. Operating times were shorter (MD, 29.88 minutes; 95% confidence interval [CI], 11.92-47.83 minutes) and hospital stays were longer (MD, -1.56 days; 95% CI, -2.27 to -0.84 days) in the LRH group compared with the LNSRH group. In addition, blood loss and the number of resected lymph nodes were not significantly different between the 2 groups. However, resected parametrium length (MD, -0.02 cm; 95% CI, -0.05 to -0.00 cm) and vaginal cuff width (MD, -0.06 cm; 95% CI, -0.09 to -0.04) were smaller in the LNSRH group. Furthermore, LNSRH tended to result in more satisfactory micturition (odds ratio, 2.90; 95% CI, 2.01-4.19), shorter catheterization time (MD, -7.20 days; 95% CI, -8.10 to -6.29 days), and shorter recovery to normal postvoid residual urine time (MD, -7.71 days; 95% CI, -8.92 to -6.50 days). Other bladder dysfunction symptoms, including urinary retention, nocturia, dysuria, urinary incontinence, and frequency/urgency were more frequent in the LRH group. Furthermore, LNSRH achieved better results in urodynamic assessments (all p < .05). In conclusion, LNSRH was associated with lower rates of impaired bladder function and a shorter extent of resection compared with LRH. Clinical applications involving LNSRH should be explored with caution.

Three-Dimensional Modelization of the Female Human Inferior Hypogastric Plexus: Implications for Nerve-Sparing Radical Hysterectomy.

BACKGROUND/AIMS: This study aims to describe the autonomic nervous network of the female pelvis with a 3D model and to provide a safe plane of dissection during radical hysterectomy for cervical cancer. METHODS: Pelvises of 3 human female fetuses were studied by using the computer-assisted anatomic dissection. RESULTS: The superior hypogastric plexus (SHP) was located at the level of the aortic bifurcation in front of the sacral promontory and divided inferiorly and laterally into 2 hypogastric nerves (HN). HN ran postero-medially to the ureter and in the lateral part of the uterosacral ligament until the superior angle of the inferior hypogastric plexus (IHP). IHP extended from the anterolateral face of the rectum, laterally to the cervix and attempted to the base of the bladder. Vesical efferences merged from the crossing point of the ureter and the uterine artery and ran through the posterior layer of the vesico-uterine ligament. CONCLUSIONS: The SHP could be injured during paraaortic lymphadenectomy. Following the ureter and resecting the medial fibrous part of the uterosacral ligament may spare the HN. No dissection should be performed under the crossing point of the ureter and the uterine artery.

Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment.

Although nonsteroidal antiinflammatory drugs can alleviate menstrual pain, about 18% of women with dysmenorrhea are unresponsive, leaving them and their physicians to pursue less well-studied strategies. The goal of this review is to provide a background for treating menstrual pain when first-line options fail. Research on menstrual pain and failure of similar drugs in the antiplatelet category suggested potential mechanisms underlying nonsteroidal antiinflammatory drug resistance. Based on these mechanisms, alternative options may be helpful for refractory cases. This review also identifies key pathways in need of further study to optimize menstrual pain treatment.

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus.

Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

Pelvic denervation procedures for dysmenorrhea.

PURPOSE OF REVIEW: Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. RECENT FINDINGS: Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. SUMMARY: Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

Pirt contributes to uterine contraction-induced pain in mice.

Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt (+/+) and Pirt (-/-) mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt (-/-) mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt (+/+) and Pirt (-/-) mice. We found that the writhing responses were less intensive in Pirt (-/-) mice than in Pirt (+/+) mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt (-/-) mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain.

A Modified Nerve-Sparing Panhysterectomy for Benign Uterine Diseases: Techniques and Evaluation of Postoperative Pelvic Dysfunctions.

OBJECTIVE: To describe a modified nerve-sparing panhysterectomy and to investigate the feasibility and impact of this nerve-sparing technique in improving postoperative pelvic visceral dysfunctions of benign uterine disease patients. METHODS: From January 2008 to January 2010, a total of 300 patients diagnosed with benign uterine diseases at the Second Affiliated Hospital of Nantong University were enrolled. Of those, 150 randomly selected patients underwent modified panhysterectomy (research group), while the other 150 patients underwent conventional panhysterectomy (control group). The surgery-related parameters, including operation time, intraoperative blood loss, length of hospital stay, postoperative indwelling catheter time, and first voiding and defecation time were compared between the two groups. The extent of nerve damage in both groups was examined using the nerve-specific marker S-100 via immunohistochemistry. Besides, postoperative assessments of bladder and bowel functions were conducted within 1 year after the operation. RESULTS: The surgery-related parameters in the two groups showed no significant difference (p > 0.05). Immunohistochemistry results showed significantly reduced damage of the nerves in the research group. We also found a better bladder and bowel function in the research group (p < 0.05) and in younger patients (p < 0.05) compared with that in the control group. Recovery trends of the bladder and bowel function were found in both groups (χ(2) = 7.512, p = 0.006 in the research group; χ(2) = 7.299, p = 0.007 in the control group). CONCLUSION: Modified panhysterectomy for benign uterine diseases seems feasible and safe, with the main advantage of improving postoperative urocystic and rectal dysfunctions through the preservation of the pelvic autonomic nerves.

Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review.

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers' presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

The opioid neuropeptides in uterine fibroid pseudocapsules: a putative association with cervical integrity in human reproduction.

The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian-cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian-cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.

Classical and nerve-sparing radical hysterectomy: an evaluation of the nerve trauma in cardinal ligament.

OBJECTIVES: This study evaluated histopathology and clinical outcome of autonomic nerve trauma and vessels removal within the cardinal ligament (CL) during nerve-sparing radical hysterectomy (NSRH) compared with radical hysterectomy (RH). METHODS: 25 women with FIGO stage Ib1-IIa cervical cancer underwent RH (n=13) or NSRH (n=12). Removed CLs lengths were measured. Biopsies were collected from the proximal, middle and distal segment of CLs and fixed. Different markers were used for immunohistochemisty analysis: tyrosine hydroxylase for sympathetic nerves; vasoactive intestinal polypeptide for parasympathetic nerves; CD34 for blood vessels; and D2-40 for lymphatic vessels. The volume density (Vv), a parameter of biological stereology, was used to quantitatively measure CL components, while post-operative functions, such as defecation, micturition and two-year disease free survival in RH and NSRH groups were compared. RESULTS: The nerves mainly existed in the middle and distal segments of CLs. The Vv was greater in RH compared with NSRH for both sympathetic and parasympathetic nerve markers (P<0.05), while the Vv of blood and lymphatic vessels were same in the two groups. Average time to achieve residual urine≤50ml and first defecation were shorter in NSRH than in RH (P<0.05). CONCLUSIONS: Less autonomic nerves within CL are transected in NSRH than in RH, while blood/lymphatic vessels are efficiently removed in both treatments. Compared to RH, NSRH decreases iatrogenic injury, which leads to reduced post-operative co-morbidities, with ensure the same radicality.

Uterine distension differentially affects remodelling and distensibility of the uterine vasculature in non-pregnant rats.

During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type.

Comparison of nerve content in removed parametrial tissue after classic radical hysterectomy and nerve-sparing radical hysterectomy--histologic evaluation.

PURPOSE OF INVESTIGATION: The aim of this study was to find whether nerve-sparing radical hysterectomy resulted in a lower amount of nerves in the removed parametrial tissue. METHODS: Histological specimens from nerve-sparing radical hysterectomy (28 cases) were compared with those obtained after classic radical hysterectomy (26 cases). Width of the parametria and vaginal cuff were measured. Using a point counting technique, nerve areal density was determined in cross sections of resected parametria at 0.5 cm (A), 1 cm (B), 1.5 cm (C) from the cervix. RESULTS: The width of the resected parametria was smaller in the study group (right side p < 0.013; left side; p < 0.011). The nerve areal density in the lateral part of the right parametrium was lower in the study group (p < 0.01) (Student's t-test). CCONCLUSION: Modified radical hysterectomy is less radical and is nerve-sparing.