Search Results (9)

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Background/Objectives: Anastomosing hemangioma (AH) is a rare, benign vascular tumor predominantly found in the genitourinary tract and often associated with impaired renal function. Due to its nonspecific radiological features, AH is frequently misinterpreted as a malignant vascular neoplasm, particularly angiosarcoma (AS), leading to potentially unnecessary surgical interventions. This study presents a systematic review of AH cases and describes a rare instance of retroperitoneal AH arising from the left gonadal vein, which was resected due to diagnostic uncertainty. Methods: A 68-year-old man underwent imaging for benign prostatic hyperplasia, incidentally revealing a 15-mm hypervascular retroperitoneal nodule adjacent to the left psoas muscle. Imaging findings, including moderate metabolic uptake on 18FDG-PET/CT, raised suspicion for AS. Given the diagnostic uncertainty and high-risk location, the multidisciplinary team (MDT) recommended surgical resection. Laparoscopic excision was performed, and histopathological analysis confirmed AH. The patient remained asymptomatic at a 22 month follow-up. In addition, a systematic review of 159 cases from 64 studies (2009–2024) was conducted to analyze radiological features, treatment approaches, and outcomes. Results: Among the reviewed cases, 68% were incidentally diagnosed, with AH occurring predominantly in the genitourinary system (70%), especially in the kidney, adrenal gland, and ovary. Chronic kidney disease (CKD) was present in 23.3% of cases, while 19.5% had a history of malignancy. Imaging was inconclusive in differentiating AH from malignancies: CT (71.9%) and MRI (6.1%) were the most used modalities, but none could reliably exclude AS. Management strategies included upfront surgical resection in 85%, while a growing proportion (9%) of cases underwent biopsy-based observation rather than immediate surgery. No cases were followed with imaging alone. Conclusions: AH remains a diagnostic challenge due to its overlap with malignant vascular tumors. While surgical excision is often performed, our review highlights an increasing trend toward conservative management with biopsy-based diagnosis. Improved awareness and the integration of histopathology, molecular markers, and MDT-based decision-making are crucial to prevent overtreatment in cases of suspected AH. Full article

Chelon labrosus represents a promising species for current aquaculture to lean towards a more sustainable model. The control of reproduction in captivity is essential to develop the industrial production of new species. This work adds to the knowledge of the reproductive aspects of males and females of this species. We aim to (1) develop a methodology for sex identification of reproductive and prereproductive specimens of the studied species based on the plasma levels of steroid hormones—estradiol (E2) and 11-ketotestosterone (11-KT); (2) determine the maturity evolution of the females throughout the spawning season by gonadal biopsy; and (3) describe sperm quality throughout the breeding season (volume, motility, density). The results show that an 11-KT/E2 ratio > 0.4 is 100% effective in distinguishing males from females, provided that individuals present a size greater than that of first sexual maturity. A double trend was observed in the development of oocytes, with an increase in the initial diameter until the middle of the spawning season, followed by a divergence of the group, with some females continuing the maturation process and others going into regression. Sperm data show stable quality at the beginning and in the middle of the spawning season and a significant loss of quality at the end of the reproductive period. The present study also shows that, between the beginning and the middle of the reproductive season, males of this species can recover sperm volume removed by stripping. Full article

The lack of data on the age, growth, and reproduction of the Atlantic Goliath Grouper Epinephelus itajara off the coasts of Florida (USA) makes it difficult to estimate the extent of their population recovery following the 1990 fishery closure, as well as the potential effects of the recent (2023) opening of a fishery for juveniles. Goliath Grouper from the Atlantic coast of Florida were non-lethally sampled for size (total length, TL), age (via fin rays), and sex and reproductive stage (via gonad biopsies, milt/egg expression, gonopores) from May to October 2010–2016. Of 653 unique fish captured (not including 118 recaptures), 257 (39.4%) were females (122–228 cm TL; 5–20 years old), 264 (40.0%) were males (104–225 cm TL; 4–22 years old), 100 (15.3%) were unsexed (82–211 cm TL; 3–15 years old), and 32 (4.9%) were protogynous hermaphrodites (108–209 cm TL; 5–20 years old). Protogyny was conclusively determined in two fish recaptured and re-biopsied that had transitioned from female to male. However, an overlap in the age and size of males and females, a 1:1 sex ratio, and the presence of relatively small, young, mature males, in combination with an apparently low functional sex change rate, all indicated that the sexual pattern of Goliath Grouper was functionally gonochoristic with the potential for diandric protogyny. Females > 10 years old were larger-at-age than males, and Goliath Grouper from the Atlantic coast were larger-at-age than fish from the Gulf of Mexico. These differences in age, growth, and reproductive strategy—as well as the nascent fishery for juveniles—need to be monitored closely so that the current and future reproductive capacity of the population continues to ensure growth and sustainability. Full article

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 MCM9 gene have been previously reported in females with premature ovarian insufficiency (POI). MCM9 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 MCM9 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 MCM9 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 MCM9 subjects has been instigated. Full article

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis. Full article

The king scallop Pecten maximus retains the amnesic shellfish poisoning toxin, domoic acid (DA), for a long time. Most of the toxin is accumulated in the digestive gland, but this organ contains several cell types whose contribution to the accumulation of the toxin is unknown. Determining the time-course of the depuration by analyzing whole organs is difficult because the inter-individual variability is high. A sampling method, using biopsies of the digestive gland, has been developed. This method allows for repetitive sampling of the same scallop, but the representativeness of the samples obtained in this way needs to be validated. In this work, we found that the distribution of DA in the digestive gland of the scallops is mostly homogeneous. Only the area closest to the gonad, and especially its outer portion, had a lower concentration than the other ones, probably due to a transfer of the toxin to the intestinal loop. Samples obtained by biopsies can therefore be considered to be representative. Most of the toxin was accumulated in large cells (mostly digestive cells), which could be due to differences during the toxin absorption or to the preferential depuration of the toxin from the small cells (mostly secretory). Full article

The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients. Full article

Objective. We present our experience in diagnosing, gender assignment, and surgical management of sexual ambiguity in 46,XY mixed gonadal dysgenesis.
Material and methods. A retrospective study of five cases treated from 2003 to 2006 was performed. Clinical picture, operative findings, testosterone levels, and immunohistochemistry of gonads for the expression of FOXL2, SOX9, AMH, AMHr, C-kit, and PLAP were analyzed.
Results. All patients had ambiguous genitalia, urogenital sinus, uterus, testicle on one side, and a streak gonad on the other. Four patients were reared as male and one as female. Stimulation by human chorionic gonadotropin showed good penile size and testosterone response. All patients underwent laparoscopic gonadal biopsy and/or gonadectomy. Histological studies showed the presence of sparse primordial follicles surrounded by embryonic sex cords in the streak portion of gonads. Germ cells were C-kit positive in all and PLAP positive in four patients. FOXL2 expression was detected in four streak gonads and in none of testes. AMH expression was found only in testes. SOX9 expression was found in both investigated testes and in three out of four streak gonads investigated.
Conclusions. 46,XY mixed gonadal dysgenesis should be differentiated from ovotesticular and other types of 46,XY disorders of sexual differentiation by the typical gonadal histology and internal genital structure. High testosterone level after stimulation and good response to testosterone treatment in 46,XY mixed gonadal dysgenesis could orient toward male sex assignment. There are different patterns of gene expression in testicular and streak gonads with a switch to FOXL2 positivity in streak gonads. Early gonadal and genital surgery is recommended. Full article