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Introduction: Robot-assisted Laparoscopic Appendicovesicostomy (RALAPV) is increasingly performed as a minimally invasive alternative to the open appendicovesicostomy (OPAV), but questions remain regarding the efficacy of the RALAPV compared to OPAV., Objective: To assess and compare outcomes for non-augmented RALAPV to the open surgical approach., Materials and Methods: An IRB approved prospective registry was retrospectively examined to abstract all patients who underwent APV without augment between 2012 and 2023. Baseline demographics, intra and post-operative characteristics, and long-term outcomes were aggregated and compared. P-values were two sided and a p-value <0.05 was considered statistically significant., Results: 52 children were identified, 19 (36.5%) OAPV and 33 (63.5%) RALAPV. The median age at surgery was 8.5 years for OAPV and 9.3 years for RALAPV (p = 0.29). Longer operative time was noted in the RALPAV group (346 min vs 289 min, p = 0.04), with a lower estimated blood loss (5 cc vs 30 cc, p = 0.003), shorter median length of hospital stay (4 days vs 5 days, p = 0.07), and lower IV morphine administration (0.04 mg/kg/d vs 0.09 mg/kg/d, p = 0.01). Similar surgical reintervention rate was seen in both cohorts (42% OAPV vs 36% RALAPV, p = 0.77). At the end of follow-up, continence was achieved in 18 (95%) OAPV and 33 (100%) RALAPV patients (p = 0.37) CONCLUSIONS: RALAPV shows comparable success to patients who underwent OPAV procedures. The longer follow-up interval for OPAV highlights minimally invasive surgery as a recent adoption., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

A comprehensive immunohistochemical ontogeny of the developing human fetal testis has remained incomplete in the literature to date. We collected human fetal testes from 8 to 21 weeks of fetal age, as well as postnatal human testes at minipuberty, pre-pubertal, and pubertal stages. Immunohistochemistry was performed with a comprehensive panel of antigens targeting gonadocytes, Sertoli cells, fetal Leydig cells, peritubular myoid cells, and other hormonal and developmental targets. Testicular cords, precursor structures to seminiferous tubules, developed from 8 to 14 weeks of fetal age, separating the testis into the interstitial and intracordal compartments. Fetal gonadocytes were localized within the testicular cords and evaluated for Testis-Specific Protein Y, Octamer-binding transcription factor 4, Sal-like protein 4, and placental alkaline phosphatase expression. Fetal Sertoli cells were also localized in the testicular cords and evaluated for SRY-box Transcription Factor 9, inhibin, and anti-Mullerian hormone expression. Fetal Leydig cells were present in the interstitium and stained for cytochrome p450c17 and calretinin, while interstitial peritubular myoid cells were examined using smooth muscle α-actin staining. Androgen receptor expression was localized close to the testicular medulla at 8 weeks and then around the testicular cords in the interstitium as they matured in structure. Postnatal staining showed that Testis-Specific Protein Y remained positive of male gonadocytes throughout adulthood. Anti-Mullerian hormone, SRY-box Transcription Factor 9, and Steroidogenic factor 1 are expressed by the postnatal Sertoli cells at all ages examined. Leydig cell markers cytochrome p450c17 and calretinin are expressed during mini-puberty and puberty, but not expressed during the pre-pubertal period. Smooth muscle α-actin and androgen receptor were not expressed during mini-puberty or pre-puberty, but again expressed during the pubertal period. The ontogenic map of the human fetal and postnatal testicular structure and expression patterns described here will serve as a reference for future investigations into normal and abnormal testicular development., (Copyright © 2022 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Ovotesticular syndrome is a rare disorder of sex development characterized by the presence of testicular and ovarian tissue. The histologic characteristics of human testicular tissue are well defined by the presence of seminiferous cords or tubules containing TSPY-positive germ cells and Sox9-positive Sertoli cells surrounded by interstitial tissue containing cytochrome P450-positive Leydig cells and smooth muscle α-actin-positive peritubular myoid cells. The histological characteristics of the ovary can be defined by germ cell nests and the development of follicles. In contrast to the testis, the ovary has a paucity of defined specific protein markers, with the granulosa cell marker FOXL2 being the most widely used. In practice, defining the ovarian component of the ovotestis can be quite difficult. We developed a model of human ovotesticular syndrome by combining fetal human testis and ovary in a xenograft model. Ovotesticular xenografts were grown under the renal capsules of gonadectomized athymic nude mice for 6-32 weeks along with age matched control grafts of fetal testis and ovary. Forty ovotesticular xenografts and their controls were analyzed by histology, immunohistochemistry, and fluorescent in situ hybridization to determine the protein expression and karyotype of the cells within the grafts. The ovotesticular xenografts exhibited recognizable testicular and ovarian tissue based on testis-specific and ovary-specific markers defined above. The xenografts simulated a bipolar ovotestis in which the testicular and ovarian elements retain their separate histological characteristics and are separated by a well-defined border. This contrasts with the compartmentalized ovotestis previously described in the literature where the testicular tissue is surrounded by ovarian tissue or a mixed histology where testicular and ovarian tissues are interspersed throughout the gonad. In conclusion, we have characterized a human model of ovotestis which will allow a deeper understanding of ovotestis development in humans and facilitate a more accurate diagnosis of the ovotesticular syndrome., (Copyright © 2021. Published by Elsevier B.V.)

The Jost hypothesis states that androgens are necessary for normal development of the male external genitalia. In this review, we explore the complementary hypothesis that estrogens can elicit abnormal development of male external genitalia. Herein, we review available data in both humans and mice on the deleterious effects of estrogen on external genitalia development, especially during the "window of susceptibility" to exogenous estrogens. The male and female developing external genitalia in both the human and mouse express ESR1 and ESR2, along with the androgen receptor (AR). Human clinical data suggests that exogenous estrogens can adversely affect normal penile and urethral development, resulting in hypospadias. Experimental mouse data also strongly supports the idea that exogenous estrogens cause penile and urethral defects. Despite key differences, estrogen-induced hypospadias in the mouse displays certain morphogenetic homologies to human hypospadias, including disruption of urethral fusion and preputial abnormalities. Timing of estrogenic exposure, or the "window of susceptibility," is an important consideration when examining malformations of the external genitalia in both humans and mice. In addition to a review of normal human and mouse external genital development, this article aims to review the present data on the role of estrogens in normal and abnormal development of the mouse and human internal and external genitalia. Based on the current literature for both species, we conclude that estrogen-dependent processes may play a role in abnormal genital development., (Copyright © 2020 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3, respectively. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling., (Copyright © 2019. Published by Elsevier B.V.)

To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling., (Copyright © 2019 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

The human penis and clitoris develop from the ambisexual genital tubercle. To compare and contrast the development of human penis and clitoris, we used macroscopic photography, optical projection tomography, light sheet microscopy, scanning electron microscopy, histology and immunohistochemistry. The human genital tubercle differentiates into a penis under the influence of androgens forming a tubular urethra that develops by canalization of the urethral plate to form a wide diamond-shaped urethral groove (opening zipper) whose edges (urethral folds) fuse in the midline (closing zipper). In contrast, in females, without the influence of androgens, the vestibular plate (homologue of the urethral plate) undergoes canalization to form a wide vestibular groove whose edges (vestibular folds) remain unfused, ultimately forming the labia minora defining the vaginal vestibule. The neurovascular anatomy is similar in both the developing human penis and clitoris and is the key to successful surgical reconstructions., (Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (<9 weeks fetal age) to well-differentiated male and female organs (>13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. We believe the images in this paper of human fetal urogenital organs produced using lightsheet fluorescence microscopy are the first published to date., (Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube., (Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

This review details methods for utilizing D & C suction abortus specimens as a source of human fetal organs to study the morphogenetic and molecular mechanisms of human fetal organ development. By this means it is possible to design experiments elucidating the molecular mechanisms of human fetal organ development and to compare and contrast human developmental mechanisms with that of laboratory animals. Finally human fetal organs can be grown in vivo as grafts to athymic mice, thus allowing ethical analysis of potential adverse effects of environmental toxicants., (Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH.

Two experiments with 72 slaughter pigs in each were conducted. Entire males and females were individually fed restricted. Palm kernel-, soybean- and fish-oil were used in varying combinations, giving different dietary fat levels (29-80g/kg) and iodine values ranging from 50 to 131. Shoulder fat was analysed for fatty acid composition (inner and outer layer), firmness and colour. A clear dose-response relationship was seen between fatty acids in diets and in shoulder fat. Interestingly, the very long chain n-3 fatty acids seemed to be deposited more efficiently when additional fat was included in the diet. Both high and low dietary iodine values changed towards less extreme iodine values in fat. Low-fat diets enhanced de novo synthesis of fatty acids. Males revealed a higher percentage of PUFA and a lower percentage of C18:1 and MUFA. Fat firmness, but not colour, was influenced by sex and dietary fat source., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A total of 72 crossbred [(Norwegian Landrace x Yorkshire) x Duroc] male and female growing-finishing pigs were restrictedly fed diets containing fish oil to study the fatty acid composition of Musculus longissimusdorsi and sensory quality of belly and neck. Six diets were used: two low-fat diets with or without 0.5% fish oil added, and four medium-fat diets with palm kernel oil to fish oil in ratios given as % inclusion: 4.1:0.0, 3.9:0.3, 3.6:0.5 and 3.4:0.7. Feeding fish oil gave a dose-dependent response between fatty acids in the diets and in the M.longissimusdorsi and increased the level of very long chain n-3 fatty acids, especially the C22:5n-3 (DPA). A more efficient n-3 fatty acids deposition was obtained when given as a medium-fat diet rather than the low-fat diet. Female pigs had a significant higher percentage of monounsaturated fatty acids and C18:1 than males suggesting a gender related difference in the delta-9-desaturase activity. No significant differences were found in sensory attributes for short-term stored neck and belly. For pigs fed the highest level of fish oil (0.7%) long-term stored (12 months at -80 degrees C, 6 months at -20 degrees C) belly showed a slight increase in fish oil flavour. After warmed-over treatment, fish oil odour and flavour as well as rancid flavour were increased in this group. The results suggest levels of dietary fish oil up to 0.5% produce a healthier meat fatty acid composition, without negative effects on sensory attributes, even in long-termed stored belly., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A total of 48 pigs (11.4 and 107.2 kg initial and final weight) were used to evaluate increasing dietary levels of bacterial protein meal (BPM) produced on natural gas (0, 50, 100, or 150 g kg(-1)) on fatty acid composition, sensory properties, and susceptibility of pork to lipid oxidation. Increasing levels of BPM to diets increased the content of C16:1 fatty acids in backfat and muscle and total monounsaturated fatty acids in muscle, but decreased the content of polyunsaturated fatty acids and iodine value in backfat and muscle. Pigs fed diets containing BPM had reduced thiobarbituric acid reactive substances (TBARS) value in backfat and muscle, reduced intensity of odor and rancid odor and taste in pork after short-time storage, and reduced off-odor and off-taste after intermediate-time storage. To conclude, adding BPM to diets for pigs changed the fatty acid profile, improved the oxidative stability, and sensory quality of pork.