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Journal of Pediatric Urology Aug 2023Anatomical studies of hypospadias show failure of zipping-up of histologically normal urethral plate and corpus spongiosum. With the commonly utilized substitution...
Post-pubertal functional outcomes of one-stage anatomical reconstruction of the corpus spongiosum, bulbo-spongiosus muscle and dartos in 46 children with proximalhypospadias.
INTRODUCTION
Anatomical studies of hypospadias show failure of zipping-up of histologically normal urethral plate and corpus spongiosum. With the commonly utilized substitution urethroplasties for proximal hypospadias, a reconstructed urethra of just an "epithelial-lined tube" with no spongiosal support, is apt to long-term urinary and ejaculatory dysfunctions. We completed a one-stage anatomical reconstruction in children with proximal hypospadias whenever the ventral curvature could be reduced to <30° and evaluated the post-pubertal outcomes.
METHOD
This is a retrospective analysis of prospectively maintained data on one-stage anatomical repair of proximal hypospadias between 2003 and 2021. In children with proximal hypospadias, the corpus spongiosum, bulbo-spongiosus muscle (BSM), Bucks', and Dartos' layers of the shaft were anatomically re-aligned prior to assessing the ventral curvature visually. When the curvature was >30°, the urethral plate was divided at the glans for a 2-stage procedure, and those patients were excluded from the study. Otherwise, the anatomical repair was continued (this series). The Hypospadias Objective Scoring Evaluation (HOSE) and the Paediatric Penile Perception Score (PPPS) were used for post-pubertal assessment.
RESULTS
Prospective records provided details of 105 patients with proximal hypospadias who had complete primary anatomical repair. The median age at surgery was 1.6 years, and 15.9 years at the post-pubertal assessment. Forty-one (39%) had complications that necessitated re-operations. Thirty-five (33.3%) patients had complications involving the urethra. For fistula and diverticula, eighteen cases required only one corrective procedure, while one required two. Other 16 patients required an average of 1.78 corrective operations for severe chordee and/or breakdown, with 7 requiring Bracka's 2-stage procedure.
RESULTS OF PUBERTAL REVIEW
Fifty patients (47.6%) were over 14 years old; 46 (92.0%) had pubertal reviews and scoring, while four were lost to follow-up. The mean HOSE score was 14.8/16, and the mean PPPS score was 17.8/18. Five patients had residual curvature of >10°. 17 and 10 patients, respectively, were unable to comment on glans firmness and ejaculation quality. During erections, 26/29 (89.7%) patients reported a firm glans, and 36/36 (100%) reported normal ejaculations.
CONCLUSION
This study proves the need for reconstruction of normal anatomy for normal post-pubertal function. In all proximal hypospadias, we strongly recommend anatomical reconstruction (zipping up) of the corpus spongiosum and BSM. When the curvature can be reduced to <30°, a complete one-stage reconstruction is possible; otherwise, anatomical reconstruction of the bulbar and proximal penile urethra is recommended, reducing the length of the epithelial-lined substitution tube for the distal shaft and glans.
Topics: Male; Child; Humans; Infant; Adolescent; Hypospadias; Retrospective Studies; Prospective Studies; Urologic Surgical Procedures, Male; Urethra; Muscles; Treatment Outcome
PubMed: 37012103
DOI: 10.1016/j.jpurol.2023.03.024 -
Biotechnic & Histochemistry : Official... Nov 2023Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine...
Diabetes mellitus (DM) is a chronic disease at all ages including childhood and puberty. Failure to treat DM can cause retinopathy, nephropathy and neuropathy. Endocrine and metabolic changes during the pubertal period complicate management of DM. Noopept is a cognitive enhancer that exhibits antidiabetic properties. We investigated the effect of noopept on the histopathology of the cornea, retina, kidney and pancreas in pubertal diabetic rats. We allocated 60 prepubertal male rats randomly into six groups of 10: untreated control (C), DM control (DC), noopept control (NC), DM + noopept (D + N), DM + insulin (D + I) and DM + insulin + noopept (D + I + N). DM was induced by streptozotocin in the DC, D + N, D + I and D + I + N groups. Noopept was administered to the NC, D + N and D + I + N groups; insulin was administered to the D + I and D + I + N groups for 14 days. On day 18 of the experiment, animals were sacrificed and eyes, kidneys and pancreata were excised for histological investigation. Renal tubule diameter and corneal and retinal thickness were increased significantly in DC groups compared to the control group. The D + I, D + N and D + I + N groups exhibited fewer DM induced pathological changes than the DC group. The D + I + N group exhibited no significant differences in renal tubule diameter and corneal and retinal thickness compared to the DC group. Our findings suggest that noopept is protective against DM end organ complications in streptozotocin induced diabetic pubertal rats.
Topics: Rats; Male; Animals; Diabetes Mellitus, Experimental; Streptozocin; Sexual Maturation; Kidney; Insulin; Pancreas
PubMed: 36946173
DOI: 10.1080/10520295.2023.2187460 -
The Journal of Veterinary Medical... May 2023Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical...
Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical cases. Recently, immunocastration has garnered popularity as a nonsurgical castration method in pig farming; however, the effects of immunocastration on cryptorchid bulls are yet to be yet. Herein, we investigated endocrine changes due to immunocastration in cryptorchid bulls and studied its effectiveness. This study included 13 Holstein bulls diagnosed with cryptorchidism and classified into two groups based on pubertal period: <8 months of age (pregroup) and ≥8 months of age (postgroup). Antigonadotropin-releasing hormone (GnRH) vaccine was used for immunocastration, and two vaccine doses were administered. Blood testosterone and anti-Müllerian hormone (AMH) levels were measured and analyzed for endocrine evaluation. The testosterone levels significantly decreased following the start of immunocastration in both groups, thereby confirming the efficacy of antiGnRH vaccination in cryptorchid bulls. The AMH levels significantly increased in the pregroup with two antiGnRH vaccination, suggesting a compensatory response via the neutralization of GnRH antibodies. The AMH levels did not significantly change in the postgroup, indicating the partial suppression of AMH secretion in Sertoli cells during sexual maturation and failure of Sertoli cell maturation. Thus, we successfully restrained the serum testosterone levels in cryptorchid bulls using antiGnRH vaccine. The testosterone levels are a useful indicator of the immunocastration effect on cryptorchid bulls. Hereafter, a vaccine program that can sustain the castration effect on cryptorchid bulls is necessary.
Topics: Male; Animals; Cattle; Swine; Gonadotropin-Releasing Hormone; Cryptorchidism; Testis; Testosterone; Vaccines; Cattle Diseases; Swine Diseases
PubMed: 36927961
DOI: 10.1292/jvms.22-0571 -
Nephrology (Carlton, Vic.) May 2023Previous studies on progression of chronic kidney disease (CKD) in children have included older post-pubertal subjects. This study attempted to evaluate risk factors for... (Observational Study)
Observational Study
AIM
Previous studies on progression of chronic kidney disease (CKD) in children have included older post-pubertal subjects. This study attempted to evaluate risk factors for progression of CKD in pre-pubertal children.
METHODS
An observational study of children aged 2-10 years with an eGFR within the limits of >30 and <75 mL/min/1.73 m was performed. Presenting clinical and biochemical risk factors, as well as diagnosis, were analysed for their association with progression to kidney failure, time to kidney failure and for the rate of decline of kidney function.
RESULTS
One hundred and twenty-five children were studied of whom 42 (34%) had progressed to CKD stage 5 during the median period of follow up of 3.1 (IQR = 1.8-6) years. Hypertension, anaemia and acidosis at entry were associated with progression but they did not predict reaching the end point. Only glomerular disease, proteinuria and stage 4 kidney disease were independent predictors of kidney failure and the time to kidney failure. The rate of kidney function decline was greater in patients with glomerular than non-glomerular disease.
CONCLUSIONS
Common modifiable risk factors, when present at initial evaluation, were not independently associated with CKD progression to kidney failure in prepubertal children. Only non-modifiable risk factors and proteinuria predicted eventual stage 5 disease. The physiological changes of puberty may be the major precipitator of kidney failure during adolescence.
Topics: Adolescent; Humans; Child; Disease Progression; Renal Insufficiency, Chronic; Risk Factors; Proteinuria; Renal Insufficiency; Glomerular Filtration Rate
PubMed: 36861372
DOI: 10.1111/nep.14153 -
Journal of Animal Science Jan 2023Successful development of replacement gilts determines their reproductive longevity and lifetime productivity. Selection for reproductive longevity is challenging due to...
Successful development of replacement gilts determines their reproductive longevity and lifetime productivity. Selection for reproductive longevity is challenging due to low heritability and expression late in life. In pigs, age at puberty is the earliest known indicator for reproductive longevity and gilts that reach puberty earlier have a greater probability of producing more lifetime litters. Failure of gilts to reach puberty and display a pubertal estrus is a major reason for early removal of replacement gilts. To identify genomic sources of variation in age at puberty for improving genetic selection for early age at puberty and related traits, gilts (n = 4,986) from a multigeneration population representing commercially available maternal genetic lines were used for a genomic best linear unbiased prediction-based genome-wide association. Twenty-one genome-wide significant single nucleotide polymorphisms (SNP) located on Sus scrofa chromosomes (SSC) 1, 2, 9, and 14 were identified with additive effects ranging from -1.61 to 1.92 d (P < 0.0001 to 0.0671). Novel candidate genes and signaling pathways were identified for age at puberty. The locus on SSC9 (83.7 to 86.7 Mb) was characterized by long range linkage disequilibrium and harbors the AHR transcription factor gene. A second candidate gene on SSC2 (82.7 Mb), ANKRA2, is a corepressor for AHR, suggesting a possible involvement of AHR signaling in regulating pubertal onset in pigs. Putative functional SNP associated with age at puberty in the AHR and ANKRA2 genes were identified. Combined analysis of these SNP showed that an increase in the number of favorable alleles reduced pubertal age by 5.84 ± 1.65 d (P < 0.001). Candidate genes for age at puberty showed pleiotropic effects with other fertility functions such as gonadotropin secretion (FOXD1), follicular development (BMP4), pregnancy (LIF), and litter size (MEF2C). Several candidate genes and signaling pathways identified in this study play a physiological role in the hypothalamic-pituitary-gonadal axis and mechanisms permitting puberty onset. Variants located in or near these genes require further characterization to identify their impact on pubertal onset in gilts. Because age at puberty is an indicator of future reproductive success, these SNP are expected to improve genomic predictions for component traits of sow fertility and lifetime productivity expressed later in life.
Topics: Pregnancy; Female; Animals; Swine; Genome-Wide Association Study; Sexual Maturation; Reproduction; Phenotype; Polymorphism, Single Nucleotide; Signal Transduction
PubMed: 36848325
DOI: 10.1093/jas/skad063 -
Frontiers in Public Health 2022Early menarche is associated with obesity, and metabolic and mental health risks, among other diseases. Thus, it is relevant to identify modifiable risk factors of early...
INTRODUCTION
Early menarche is associated with obesity, and metabolic and mental health risks, among other diseases. Thus, it is relevant to identify modifiable risk factors of early menarche. Some nutrients and foods have been linked to pubertal timing, but how menarche relates to overall dietary patterns is unclear.
METHODS
The aim of this study was to analyze the association between dietary patterns and age at menarche in a prospective cohort of Chilean girls from low and middle-income families. We conducted a survival analysis of 215 girls (median = 12.7 years, IQR = 12.2-13.2) from the Growth and Obesity Cohort Study (GOCS) who had been followed prospectively since 4 years of age (2006). Age at menarche and anthropometric measurements were recorded every 6 months since 7 years of age while diet (24-hour dietary recall) was collected for 11 years. Dietary patterns were obtained from exploratory factor analysis. Accelerated Failure Time models adjusted for potential confounding variables were used to study the association between dietary patterns and age at menarche.
RESULTS
Girls' median age at menarche was 12.7 years. Three dietary patterns were identified: "Breakfast/Light Dinner," "Prudent" and "Snacking" which explained 19.5% of the diet variation. Girls in the lowest tertile of the "Prudent" pattern had menarche 3 months earlier than girls in the highest tertile (β: 0.022; 95% CI: 0.003; 0.041). "Breakfast/Light Dinner" and "Snacking" patterns were not associated with age at menarche.
CONCLUSION
Our results suggest that healthier dietary patterns during puberty might be associated with menarche timing. Nevertheless, further studies are required to confirm this result and to clarify the association between diet and puberty.
Topics: Female; Humans; Adolescent; Child; Menarche; Cohort Studies; Prospective Studies; Chile; Diet; Obesity
PubMed: 36793361
DOI: 10.3389/fpubh.2022.995593 -
Journal of Clinical Medicine Jan 2023Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are,...
Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the gene have been previously reported in females with premature ovarian insufficiency (POI). is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic subjects has been instigated.
PubMed: 36769638
DOI: 10.3390/jcm12030990 -
Hormone Research in Paediatrics 2023The metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) cleaves insulin-like growth factor (IGF)-binding proteins 3 and 5 to release bioactive IGF-I from...
INTRODUCTION
The metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) cleaves insulin-like growth factor (IGF)-binding proteins 3 and 5 to release bioactive IGF-I from its ternary complex. Patients with mutations in PAPP-A2 have growth failure and low free IGF-I despite elevated total IGF-I. We describe 5-year treatment response to recombinant human IGF-1 (rhIGF-1) in a patient with PAPP-A2 deficiency, and the phenotype of PAPP-A2 deficiency in three siblings.
METHODS
Two siblings (P2, P3) with PAPP-A2 deficiency were recruited for rhIGF-1 therapy at 120 μg/kg subcutaneous twice daily, along with a third sibling (P1) for phenotyping. We evaluated efficacy and safety of rhIGF-1 therapy, including effect on metabolic measures and bone mineral density (BMD).
RESULTS
Treatment with rhIGF-1 was started in 10.4-year- (P3) and 14.5-year (P2)-old brothers. P2 discontinued therapy due to pseudotumor cerebri. P3 continued rhIGF-1 for 5 years; height velocity increased (3.0 cm/year at baseline; 5.0-7.6 cm/year thereafter) as did height SDS (+0.6). P3's pubertal onset was at 12.4 year. BMD height-adjusted Z-score modestly improved for lumbar spine (+0.4), and decreased in forearm (-0.2) and hip (-0.3). All siblings had hyperinsulinemia. Impaired glucose tolerance (IGT) resolved in P1. P2 showed worsening glucose tolerance (2-h glucose: 225 mg/dL). Impaired fasting glucose and hyperinsulinemia initially resolved for P3, but IGT (2-h glucose: 152 mg/dL) developed during puberty.
CONCLUSION
Therapy with rhIGF-1 modestly improved linear growth in one patient with PAPP-A2 deficiency, but without true catch-up. Therapy was associated with pseudotumor cerebri in a sibling. Initial improvement in BMD and glycemic pattern on rhIGF-1 was not sustained during puberty.
Topics: Male; Humans; Insulin-Like Growth Factor I; Pseudotumor Cerebri; Glucose; Recombinant Proteins; Glucose Intolerance; Hyperinsulinism
PubMed: 36646053
DOI: 10.1159/000529071 -
Biology of Sex Differences Jan 2023GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot (leuprolide...
Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination.
BACKGROUND
GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot (leuprolide acetate), have been used to suppress pubertal progression in adolescents who are questioning their gender identity. However, few preclinical studies have been conducted to investigate potential effects of using GnRH agonists in this context.
METHODS
The present study tested the effects of daily leuprolide treatment (50 µg/kg, postnatal day (PD) 25-50) on pubertal onset in female (i.e., vaginal opening) and male (i.e., preputial separation) Long-Evans rats. The first estrous cycle immediately after vaginal opening was also measured. Sexual behavior and sexual motivation were tested using the partner-preference paradigm. Female rats were tested during the first behavioral estrus after treatment ended (between PD 51-64). Male rats were tested weekly for four consecutive weeks starting three days after treatment ended (PD 53).
RESULTS
Consistent with previous findings, leuprolide significantly delayed pubertal onset in both female and male rats. In addition, the first estrous cycle during the treatment period was disrupted by leuprolide, as indicated by a failure to cycle into estrus after vaginal opening until treatment ended. However, leuprolide affected neither sexual motivation nor fertility when female rats were tested within 14 days of leuprolide treatment ending. In contrast, the development of copulatory behavior and sexual motivation was significantly delayed by leuprolide in male rats; however, mature reproductive behavior was observed by the fourth week post-treatment.
CONCLUSIONS
Taken together with previous findings, the present results indicate that male rats may be more sensitive to periadolescent leuprolide administration, taking longer to overcome the effects of leuprolide than female rats. Nevertheless, not long after leuprolide treatment is discontinued, sex-typical reproductive physiology and behavior emerge fully in female and male rats, indicating that the drug's effects are not permanent. If translatable to humans, leuprolide may be a reversible option to give adolescents more time to consider their gender identity with minimal long-term effects on sexual development.
Topics: Humans; Child; Rats; Female; Male; Animals; Adolescent; Leuprolide; Rats, Long-Evans; Gender Identity; Puberty, Precocious; Estrus
PubMed: 36609535
DOI: 10.1186/s13293-022-00485-5 -
Frontiers in Endocrinology 2022Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH... (Review)
Review
Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH stimulation tests (GHSTs) is needed to confirm GHD, but long-standing controversies regarding the number of tests needed and the interpretation of GH peaks are still a matter of debate worldwide. Diagnostic workup is even more problematic in short children with slow growth and delayed sexual development: they often exhibit low GH peaks under GHST, which often normalize as puberty progresses. Consequently, this transient suboptimal response to GHST may result in GH overtreatment, carrying both health and economic concerns. Considering the complex and bound link between GH axis and sex steroids, the use of sex steroid priming prior to GHST might be helpful in peripubertal setting. However, its use is still controversial. There is no consensus regarding patient selection, timing, dose, and preparation of sex steroids. In this review, we aim to overview the use of sex steroid priming in clinical practice, highlighting the need to develop appropriate guidelines in order to overcome diagnostic pitfalls in peripubertal age.
Topics: Humans; Child; Human Growth Hormone; Dwarfism, Pituitary; Gonadal Steroid Hormones; Puberty; Hypopituitarism; Steroids
PubMed: 36523598
DOI: 10.3389/fendo.2022.1072271