46,XX Differences of Sex Development outside congenital adrenal hyperplasia: pathogenesis, clinical aspects, puberty, sex hormone replacement therapy and fertility outcomes.

The term 'differences of sex development' (DSD) refers to a group of congenital conditions that are associated with atypical development of chromosomal, gonadal, and/or anatomical sex. DSD in individuals with a 46,XX karyotype can occur due to fetal or postnatal exposure to elevated amount of androgens or maldevelopment of internal genitalia. Clinical phenotype could be quite variable and for this reason these conditions could be diagnosed at birth, in newborns with atypical genitalia, but also even later in life, due to progressive virilization during adolescence, or pubertal delay. Understand the physiological development and the molecular bases of gonadal and adrenal structures is crucial to determine the diagnosis and best management and treatment for these patients. The most common cause of DSD in 46,XX newborns is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, determining primary adrenal insufficiency and androgen excess. In this review we will focus on the other rare causes of 46,XX DSD, outside CAH, summarizing the most relevant data on genetic, clinical aspects, puberty and fertility outcomes of these rare diseases.

Comparison of Fat Transfer Combined with Plasma Energy and Only Fat Transfer Methods for Genital Rejuvenation.

BACKGROUND: To compare the fat transfer combined with plasma energy and only fat transfer methods for genital rejuvenation and to investigate the efficacy enhancing properties of plasma energy. METHODS: Forty-six patients were equally divided into two groups according to the surgical method as the group A (n = 23) and the group B (n = 23). The patients in the group A received only fat transfer, while the patients in the group B received fat transfer combined with plasma energy. Both groups were scheduled for postoperative follow-up at 1, 3, 6, and 12 months. The lifting effect on the labia majora after the procedure was evaluated with photographs and patient satisfaction questionnaires including the female genital self-image scale (FGSIS). RESULTS: The mean age of all participants was 32.8 ± 5.1 years, and the mean body mass index (BMI) was 24.7 ± 3.4 kg/m2. The mean preoperative FGSIS scores were similar between the groups (p = 0.542). The mean total FGSIS score was 18.8 ± 1.4 in the group A and 18.3 ± 1.5 in the group B in the preoperative period. However, the mean FGSIS scores at 1, 3, and 6 months were significantly higher in the group B than the group A (p = 0.032, p = 0.012, and p = 0.009, respectively). At 6 months of follow-up, the mean total FGSIS score was 20.7 ± 1.4 in the group A and 22.3 ± 1.5 in the group B, indicating a statistically significant difference (p = 0.028). CONCLUSION: This novel technique is a more minimally invasive technique compared to other energy modalities with lower lateral and vertical energy dissipation than other conventional methods, and labia majora fat filling augmentation application can be performed with more permanent and longer-lasting outcomes than fat transfer only. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Observations on the anatomy of the funiculus spermaticus and the testis in Brachyteles sp. (SPIX, 1823) primates - Atelidae.

BACKGROUND: Analysing the literature about the reproductive anatomy on New World Primates, one can see the need of standardisation on the description methods and, more importantly, the lack of detailed information. The problem is aggravated by the difficult access to specimens of the endangered species such as Brachyteles sp. This paper's objective was to extend knowledge on the male reproductive anatomy of these primates. The testis and funiculus spermaticus of Brachyteles are described in detail. METHODS: We utilised one individual of Brachyteles arachnoides, two hybrids (B. arachnoides × Brachyteles hypoxanthus) and photographs of the testis of a third fresh specimen of a hybrid individual. RESULTS: The septum formed by tunica dartos adheres to the testis and separates the scrotum in two testicular cavities. Passed the spermatic cord, the external spermatic fascia continues with the tunica dartos, covering the cranial half of the testis. The fascia cremasterica divides itself in bundles of fibres and forms loops around the testicles creating a sac like structure that seems to be unique among Neotropical Primates. The appendix testis is described for the first time in platyrrhini. It is presented as a sessile structure in the extremitas capitata of the testis. Previous literature on the reproductive anatomy of platyrrhini is limited. Despite that, it can be said that the large size and volume of the testis, and complex structure of the cremaster, could consist of a heat loss reduction strategy in cold and humid forest environments. CONCLUSIONS: Except for the larger size of the testicles in hybrid individuals, no other significant morphological differences were found between B. arachnoides and hybrids (B. arachnoides × B. hypoxanthus).

Moment of induction and duration of experimental varicocele in rats: effects on semen quality.

PURPOSE: Varicocele is a condition known to cause damage to seminal parameters and sperm function. Furthermore, it has been hypothesized that the varicocele effect on fertility is time-dependent; however, little is known about the consequences of its establishment time on reproductive organs and/or sperm function. This study aimed to evaluate the effect of the duration of experimental varicocele on reproductive organs, sperm parameters, and sperm function. MATERIALS AND METHODS: Varicocele induction surgeries were performed in Wistar rats aged 40 or 100 days old. At 160-day-old, analyses were performed, including biometry of reproductive organs (prostate, seminal vesicles, epididymis, and testis), sperm parameters (vitality, morphology, and motility), and sperm function tests (nuclear DNA integrity, acrosome integrity, and mitochondrial activity). RESULTS: The analysis of the biometry of reproductive organs showed no differences between distinct ages in which varicocele was induced. The total abnormal sperm morphology was bigger in animals with varicocele induced to 100 days old than in animals with varicocele induced to 40 days old. Regarding nuclear DNA integrity, animals of varicocele induced to 100 days old showed worse results compared to animals of varicocele induced to 40 days old. Other parameters analyzed showed no differences between varicocele groups. CONCLUSION: In this study conducted on rats, we conclude that varicocele adversely affects sperm, particularly its function. However, we did not observe a negative progressive effect on sperm.

Next step in Monachacantiana (Montagu, 1803) phylogeography: northern French and Dutch populations (Eupulmonata, Stylommatophora, Hygromiidae).

Features of shell and genitalia as well as nucleotide sequences of selected mitochondrial and nuclear genes of specimens of Monachacantiana from ten northern French and two Dutch populations were compared with the same features of British and Italian populations. They were found to be very similar to populations previously identified as belonging to the CAN-1 lineage of M.cantiana. This confirms previous suggestions that M.cantiana was introduced to western Europe (England, France and the Netherlands) in historical times.

Unusual morphology of isolated male epispadia: A rare case report.

In less than 10% of cases, males may have isolated epispadias, which is caused by failure in the urethral tubularization process, leading to dorsal urethral defect. This case report presents a unique instance where epispadias was associated with ambiguous genitalia. A 5-year-old boy diagnosed with epispadias. The penis resembled external female genitalia, with scrotal skin covering it. He underwent a two-stage operation without complications. The aim of the surgical techniques is to correct these anomalies and restore urinary continence and sexual function. Long-term outcomes of the surgery can vary, which highlights the need for further research.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

A rare case of Fournier's gangrene developing from colon perforation in an infant: A case report.

Fournier's gangrene, a rare and life-threatening soft tissue infection affecting the genitalia and perineum, results from various microorganisms. This rapidly progressing necrotizing fasciitis yields higher mortality and morbidity rates. We report a case of a 1-month-old male infant with Fournier's gangrene due to perforation transverse colon complicated with septic shock and pneumonia also accompanied by patent processus vaginalis. Radiological findings of pneumonia and pneumoperitoneum were exhibited. Early diagnosis and management are demanded to mitigate life-threatening and improve the prognosis. The patient underwent incision drainage, peritoneal lavage, exploratory laparotomy, colostomy, necrotomy debridement, and patent processus vaginalis ligation after hemodynamic status stabilization.

Imperforate Hymen: A Report of a Case With Classical Signs.

An imperforate hymen (IH) is a condition where the hymen, which is a thin membrane that partially covers the vaginal opening, completely obstructs the vaginal canal. This condition is associated with problems such as pelvic mass, cyclical abdominal discomfort, and difficulty in urination. The occurrence of IH is quite rare, with an incidence of only one in 1000-10,000 women worldwide. We discuss a classical case of primary amenorrhoea with associated complaints of urinary retention and its management by hymenotomy (cruciate incision). We also considered the risk of hymen re-closure due to the lack of estrogenization of genital tissue and offered the patient the option of vaginal molding.

Not all apparently gynandromorphic butterflies are gynandrous: The case of Polyommatus icarus and its relatives (Lepidoptera: Lycaenidae).

Beside the more than two thousand normal specimens of Polyommatus icarus (Rottemburg, 1775) yielded by rearing experiments, there was one perfectly bilateral dichromatic individual first considered to be gynandrous. On the basis of analysing genitalia traits, wing surface covering scale micromorphology, and the spectral characteristics of the blue colour generated by the cover scales, the gender of the specimen has been identified as female. This exemplar was investigated in comparison with gynandrous specimens from the collections of the Hungarian Natural History Museum exhibiting various degrees of intermixing of blue and brown coloration. Focus stacking microscopy for detailed scale morphology and UV-visible reflectance spectroscopy was used for the characterization of the optical properties. Inspecting literature references and the Lycaenidae collection of the museum, further examples have been found for female bilateral dichromatism in the closely related polyommatine lycaenid species Lysandra bellargus (Rottemburg, 1775) and Lysandra coridon (Poda, 1761) what suggests that polyommatine female dichromaticity may be displayed by the manner of bilaterality and mosaicism, phenomena hitherto solely connected to gynandromorphy.

Identification of a novel homozygous NR5A1 variant in a patient with a 46,XY disorders of sex development.

OBJECTIVES: Nuclear receptor subfamily 5 group A member 1 (NR5A1) is a transcription factor critical for the development of various organs. Pathogenic variants in NR5A1 are associated with a spectrum of disorders of sex development (DSD). CASE PRESENTATION: A 15-month-old baby, raised as a girl, was referred for genital swelling and ambiguous genitalia. Born to healthy consanguineous parents, the baby had a phallus, perineal hypospadias, labial fusion, and a hypoplastic scrotum. Hormonal evaluation showed normal levels, and ultrasonography revealed small gonads and absence of Müllerian derivatives. Post-human chorionic gonadotropin (hCG) testing indicated an adequate testosterone response. The karyotype was 46,XY, and in it was found a homozygous NR5A1 variant (c.307 C>T, p.Arg103Trp) in a custom 46 XY DSD gene panel. Notably, the patient exhibited complete sex reversal, hyposplenia, and no adrenal insufficiency. CONCLUSIONS: Previously, NR5A1 pathogenic variants were considered to be dominantly inherited, and homozygous cases were thought to be associated with adrenal insufficiency. Despite the homozygous pathogenic variant, our patient showed hyposplenism with normal adrenal function; this highlights the complexity of NR5A1 genotype-phenotype correlations. These patients should be monitored for adrenal insufficiency and DSD as well as splenic function.

Two new species of the hyperdiverse geometrid moth genus Eois (Lepidoptera, Geometridae, Larentiinae) from Ecuador, with descriptions of early stages.

The hyperdiverse geometrid genus Eois Hübner, estimated to encompass more than 1,000 species, is among the most species-rich genera in all of Lepidoptera. While the genus has attracted considerable attention from ecologists and evolutionary biologists in recent decades, limited progress has been made on its alpha taxonomy. This contribution focuses on the Olivacea clade, whose monophyly has been recognized previously through molecular analyses. We attempt to define the clade from a morphological perspective and recognize the following species based on morphology and genomic data: E.olivacea (Felder & Rogenhofer); E.pseudolivacea Doan, sp. nov.; E.auruda (Dognin), stat. rev.; E.beebei (Fletcher, 1952), stat. rev.; E.boliviensis (Dognin), stat. rev.; and E.parumsimii Doan, sp. nov. Descriptions and illustrations of the immature stages of E.pseudolivacea reared from Piper (Piperaceae) in Ecuador are provided.

A developmental atlas of male terminalia across twelve species of Drosophila.

How complex morphologies evolve is one of the central questions in evolutionary biology. Observing the morphogenetic events that occur during development provides a unique perspective on the origins and diversification of morphological novelty. One can trace the tissue of origin, emergence, and even regression of structures to resolve murky homology relationships between species. Here, we trace the developmental events that shape some of the most diverse organs in the animal kingdom-the male terminalia (genitalia and analia) of Drosophilids. Male genitalia are known for their rapid evolution with closely related species of the Drosophila genus demonstrating vast variation in their reproductive morphology. We used confocal microscopy to monitor terminalia development during metamorphosis in twelve related species of Drosophila. From this comprehensive dataset, we propose a new staging scheme for pupal terminalia development based on shared developmental landmarks, which allows one to align developmental time points between species. We were able to trace the origin of different substructures, find new morphologies and suggest possible homology of certain substructures. Additionally, we demonstrate that posterior lobe is likely originated prior to the split between the Drosophila melanogaster and the Drosophila yakuba clade. Our dataset opens up many new directions of research and provides an entry point for future studies of the Drosophila male terminalia evolution and development.

Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 coactivator, identifying wingless/integrated (WNT) signaling as a highly enriched AR-regulated pathway in the genitalia. Transcription factor (TF) hits were then assayed for sexually dimorphic expression at two critical time points and also cross-referenced to a database of clinically relevant copy number variations to identify 252 TFs exhibiting copy variation in patients with LGU phenotypes. A subset of 54 TFs was identified for which LGU phenotypes are statistically overrepresented as a proportion of total observed phenotypes. The 252 TF hitlist was then subjected to a functional screen to identify hits whose silencing affects genital mesenchymal growth rates. Overlap of these datasets results in a refined list of 133 TFs of both functional and clinical relevance to LGU development, 31 of which are top priority candidates, including the well-documented renal progenitor regulator, Sall1. Loss of Sall1 was examined in vivo and confirmed to be a powerful regulator of LGU development.

Discovery of five new species of Allacta from Yunnan and Hainan, China (Blattodea, Pseudophyllodromiidae).

We examined new Allacta materials from Yunnan and Hainan Province, China, and discovered new species using both morphological and molecular species delimitation (ABGD) methods. Five new species are described: A.bifolium Li & Wang, sp. nov., A.hemiptera Li & Wang, sp. nov., A.lunulara Li & Wang, sp. nov., A.redacta Li & Wang, sp. nov., and A.unicaudata Li & Wang, sp. nov. All five species are placed under the hamifera species group. An updated key and checklist of Allacta species from China are provided.

Sox21b underlies the rapid diversification of a novel male genital structure between Drosophila species.

The emergence and diversification of morphological novelties is a major feature of animal evolution.1,2,3,4,5,6,7,8,9 However, relatively little is known about the genetic basis of the evolution of novel structures and the mechanisms underlying their diversification. The epandrial posterior lobes of male genitalia are a novelty of particular Drosophila species.10,11,12,13 The lobes grasp the female ovipositor and insert between her abdominal tergites and, therefore, are important for copulation and species recognition.10,11,12,14,15,16,17 The posterior lobes likely evolved from co-option of a Hox-regulated gene network from the posterior spiracles10 and have since diversified in morphology in the D. simulans clade, in particular, over the last 240,000 years, driven by sexual selection.18,19,20,21 The genetic basis of this diversification is polygenic but, to the best of our knowledge, none of the causative genes have been identified.22,23,24,25,26,27,28,29,30 Identifying the genes underlying the diversification of these secondary sexual structures is essential to understanding the evolutionary impact on copulation and species recognition. Here, we show that Sox21b negatively regulates posterior lobe size. This is consistent with expanded Sox21b expression in D. mauritiana, which develops smaller posterior lobes than D. simulans. We tested this by generating reciprocal hemizygotes and confirmed that changes in Sox21b underlie posterior lobe evolution between these species. Furthermore, we found that posterior lobe size differences caused by the species-specific allele of Sox21b significantly affect copulation duration. Taken together, our study reveals the genetic basis for the sexual-selection-driven diversification of a novel morphological structure and its functional impact on copulatory behavior.

Review of the genus Prochasma Warren (Geometridae, Ennominae, Boarmiini), with description of a new species from Hainan, South China.

The few already published generic features of the genus Prochasma Warren, 1897 are reviewed and new-found characters are added to make the generic description more comprehensive. A new species, Prochasmadiaoluoensis Liu & Stüning, sp. nov. is described from Hainan Province, China. It is the only Prochasma species found on this island and exceptional for its conspicuous pattern, vivid coloration and some morphological characters not observed in other species before. Descriptions and illustrations of adults, their venation, and male and female genitalia are presented. An identification key and an annotated checklist of all presently known species of Prochasma are provided. In addition, a DNA barcode sequence is given for the new species, and preliminary phylogenetic estimations of the genus Prochasma are discussed.

Adult Outcome After Partial Androgen Insensitivity Syndrome: Diagnosed and Assigned Female in Infancy.

This patient, now in her 40s, was evaluated because of genital ambiguity and diagnosed with pAIS in infancy based upon elevated testosterone and gonadotropin levels and significantly reduced binding affinity of the androgen receptor. Such reduced binding is consistent with a structural abnormality of the receptor protein precluding expected activity of the androgen receptor. Based on this information and counseling, her parents chose a female sex assignment. She had clitoral recession and testes removal as an infant and neovaginal surgery using a distal ileum segment at age 11 years and was begun on estrogen therapy at age 12 years. She is being reported now to point out that the data known at her birth provided as specific information to guide sex assignment and genital surgery as is currently available. More importantly, long-term outcome data is very positive showing clear female gender identity, successful marriage of more than 20 years, excellent social relationships including family and friends, an active social life. Since this diagnosis is lifelong, it is inevitable that there will be reminders, hopefully rare, that may be traumatizing. Unfortunately, in this patient, such reminders have been related to access to health care.