Puberty Research Articles

Effect of egg incubator temperature on sex differentiation in Korat chickens

The effect of incubator temperature on sex differentiation in Korat chickens was investigated. The experiments were divided into two sets: temperature applied throughout the entire incubation period and temperature applied during certain periods (days 3-6 of incubation) by either increasing above the standard or decreasing below the standard temperature. In each experiment, 300 Korat chicken eggs were separated into three groups of 5 repetitions, with 20 eggs in each group. This was done using a completely randomized design for each experiment: a group using a temperature below the standard for incubation (36.0°C), a group using the standard incubation temperature (37.7°C), and a group using a temperature above the standard for incubation (38.0°C). W chromosomes were detected at hatch; histology examined reproductive structures after 35 days. Increasing the temperature to 38.0°C throughout the entire incubation period resulted in no significant difference in hatching rates compared to the standard temperature (P>0.05). Raising the temperature to 38.0°C throughout the entire incubation and during certain periods resulted in changes in the reproductive structure of chickens, leading to a mismatch between chromosomal and gonadal sex, observed at 9.7% and 5.9% of individuals with W chromosomes possessed testes, indicating a mismatch between chromosomal and gonadal sex. However, decreasing the temperature to 36.0°C throughout the incubation period resulted in lower hatching rates compared to the standard temperature (P<0.05). Incubating eggs at 36.0°C for specific periods resulted in 19.4% of genetic males developing ovaries instead of testes. The presence of ovaries in individuals without W chromosomes indicated this mismatch. The results of this study provide evidence that temperature plays a role in sex differentiation in Korat chickens, as demonstrated by the detection of W chromosomes and histological studies of testes and ovaries. Moreover, this study presents the first evidence in broilers that temperature can affect sex differentiation.

Cryptorchidism: An update of advances in its diagnosis and treatment

The absence of one or both testicles in the scrotal position is defined as cryptorchidism. It occurs in 1 - 8 % of full-term newborns and up to 45 % of preterm newborns. Its detection is of great importance due to its association with fertility disorders and the risk of malignancy. The National Endocrinology Committee of the Sociedad Argentina de Pediatría decided to prepare an update document on advances in the diagnosis and treatment of cryptorchidism that contributes to the performance of pediatric practice and allows recognition of conditions that may be accompanied by cryptorchidism, but need more evaluation and referral to a specialist, such as alterations/differences in sexual development, anorchia, genetic syndromes, among others. The first-line treatment is early orchiopexy before 12 to 18 months, always in the hands of pediatric surgeons.

Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry

Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, which participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l-/- are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l+-germ cells; these cells failed to enter meiosis and accumulated as cystic cells in the foxl2l-/- mutant. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells.

Peculiarities of the menstrual cycle in girls living in the Murmansk region

The aim of the study. To assess the characteristics of the menstrual cycle and ovulation disorders in girls aged 15–17 years.Materials and methods. The study was carried out in 2022–2023 in the Murmansk region in Apatity. A total of 225 girls with average age of 16.5 ± 0.03 years took part in the study. The characteristics of the menstrual cycle and ovulation disorders were studied according to the guidelines of the International Federation of Gynecology and Obstetrics.Results of the study. In the study group, the onset of menarche (13.1 years) is observed at a later age compared to the girls living in other regions of Russia and neighboring countries (12.6–12.9 years). Every seventh girl has an irregular menstrual cycle, every fifth girl has a cycle duration of more than 38 days. Heavy menstruation occurs in every third girl, intermenstrual uterine bleeding – in every thirteenth girl. Half of the girls have painful periods (dysmenorrhea). Among ovulation disorders, the most common is abnormal uterine bleeding – 34.7 %. Also, intermenstrual uterine bleeding (8.0 %), primary amenorrhea (2.7 %) and polycystic ovary syndrome (1.3 %) are registered. Among gynecological pathology, in addition to ovulation disorders, we registered vulvovaginal candidiasis and paraurethral cyst.Conclusion. The analysis of the obtained results showed that only 20.4 % of girls do not have gynecological pathology, which to a certain extent indicates a low level of reproductive health of girls. Asaresult, it is necessary to diagnose and treat diseases which can cause the development of ovulation disorders more carefully and at earlier stages of sexual development. The work was carried out as part of the research topic No. FMEZ-2022-0012.

Disorders of Sex Development (DSD): A more than three Decades of Experience at a Major Teaching Hospital

A retrospective hospital-based study was conducted at the Pediatric Endocrine Division, King Khalid University Hospital (KKUH), King Saud University, Riyadh, Saudi Arabia, during the period July 1983 and June 2017. Methods: Medical records of patients who were diagnosed with DSD were retrospectively reviewed. Data included the etiological diagnosis, clinical history, physical examination, results of laboratory and radiological investigations, medical and surgical options offered, and results of follow-up. Laparoscopy or laparotomy with gonadal biopsies was done when appropriate. Results: During the period under review, a total of 203 patients with Disorders of Sex Development (DSDs) were evaluated. Their ages ranged between one day and 13 years. Hundred- thirty-nine (68.5%) patients were genetic females (46 XX). Congenital Adrenal Hyperplasia (CAH) is the most common, in 137(98.5%) patients. Conclusion: Disorders of sex development are a group of heterogeneous conditions with variable aetiologias. Many patients with DSD have a good quality of life and lead a near-normal life, though some have not. The severity of the disorder, initial evaluation and follow-up by a specialized multidisciplinary team, good psychological support, and proper education were important. Finally, sex assignments should be made early after a thorough investigation.

Exploring the clinical implications of novel SRD5A2 variants in 46,XY disorders of sex development.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2, and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.

Global, regional, and national burdens of Alzheimer's disease and other forms of dementia in the elderly population from 1999 to 2019: A trend analysis based on the Global Burden of Disease Study 2019

AbstractDementia represents a significant health issue, afflicting both patients and their families. To assess the global trends in the incidence, prevalence, mortality, and disability‐adjusted life years (DALYs) of Alzheimer's disease (AD) and other dementias in the elderly population, the Global Burden of Disease Study (1999−2019) was used. The average annual percentage change (AAPC) was estimated using linear regression. Stratified analysis of the global trends by age, sex, region, national level, and social development index (SDI) were also performed. The global incidence of AD and other dementias increased from 507.96 per 100,000 in 1990 to 569.39 per 100,000 in 2019, showing a significant increase in this period. In males, the incidence increased from 387.56 per 100,000 population in 1990 to 462.40 per 100,000 in 2019 (AAPC = 0.61), whereas females experienced a slower rise (AAPC = 0.31) and had a higher incidence in 2019 (662.93 per 100,000 population). The most significant increase was observed in individuals aged 60−64 and those in the middle‐SDI quintile. Regionally, the high‐income Asia Pacific had the highest incidence (890.01 per 100,000 population) and DALYs (3043.86 per 100,000) in AD and other dementias in 2019. As for national trends, Japan had the most pronounced increase in the incidence and DALYs of AD and other dementias during the 1990−2019 period. These findings highlight the growing burden of dementias on life expectancy at a population level, which is significant for healthcare professionals and decision‐makers to conduct the ongoing debate on the policy of AD and other dementias.

A 10-Year Retrospective Study: Is Maternal Diabetes a Risk Factor for Associated Anomalies in Males With Cryptorchidism?

Background and objective Cryptorchidism, or undescended testes (UDT), refers to the failure of one or both testicles to descend to their natural position in the scrotum of newborn males. The association of gestational diabetes with cryptorchidism has not been studied sufficiently. Hence, this study aimed to analyze the association between maternal diabetes and cryptorchidismand other associated anomalies among Jordanian male children. Methods We conducted a retrospective studyinvolving women and their cryptorchid offspring over a 10-year period, between January 2010 and December 2019. The data were collected using a retrospective review of the hospital records and questionnaires administered via phone calls. We included all patients with cryptorchidism and excluded children with a diagnosis of disorders of sexual development. Results A total of 368 children with cryptorchidism were included, with 29 mothers suffering from gestational or type II diabetes at the time of pregnancy. About 25% of patients suffered from associated anomalies, the most common being genital anomalies, while hypospadias was the most common associated anomaly. We observed no differences in terms of the age of diagnosis or treatment of cryptorchidism between children born to diabetic and those born to nondiabetic mothers. Conclusions Diabetic mothers have a higher chance of having offspring with anomalies that might co-occur with cryptorchidism, particularly urogenital anomalies. Further research is needed to explore the link between maternal diabetes and these abnormalities. Screening for gestational diabetes is critical, and more extensive studies could provide clearer recommendations for screening protocols and early intervention.

Influence of Smartphone Usage on development of Sexuality among Late Adolescent Boys in Health Sciences Colleges of South India

Background Better affordability of data plans and an increase in “budget” smartphones have resulted in an exponential rise in internet and smartphone users. The ease of access to sexually explicit material (SEM) coupled with adolescents’ impulsivity makes them prone to excessive SEM exposure and may affect the development of sexuality via the perceived realism of such content. This study was done to study the influence between problematic smartphone usage (PSU) and sexuality development among late adolescent boys. Methods One hundred and thirty-four adolescents aged 18-19 years, studying in a medical university, participated in this cross-sectional study. Smartphone Addiction Scale – short version (SAS-SV) to evaluate PSU and a content validated semi-structured proforma to evaluate gender identity, sexual orientation, sources of information on pubertal changes, and exposure to pornographic content was used. We expressed results as proportion and summary measures (Mean±SD), Chi-square test to find influence between PSU and adolescent sexuality development. Results We found a 45.5% prevalence of PSU. Among study participants, 88% were attracted to the opposite sex, 6% were attracted to the same-sex, and 6% were attracted to both sexes. Three per cent of participants liked wearing clothes of the opposite sex, 7.5% wanted to be members of the opposite sex, whereas 10.4% were not comfortable with their genitalia. They obtained information regarding pubertal changes from friends (85) and media (78). Many had exposure to pornographic content (90%), with the youngest being nine years old. Conclusion Nearly half of the late adolescents have PSU. Pornographic contents are accessed through Smartphones.

NR5A1/SF-1 Collaborates with Inhibin α and the Androgen Receptor.

Steroidogenic factor 1 (SF-1) is a nuclear receptor that regulates steroidogenesis and reproductive development. NR5A1/SF-1 variants are associated with a broad spectrum of phenotypes across individuals with disorders of sex development (DSDs). Oligogenic inheritance has been suggested as an explanation. SF-1 interacts with numerous partners. Here, we investigated a constellation of gene variants identified in a 46,XY severely undervirilized individual carrying an ACMG-categorized 'pathogenic' NR5A1/SF-1 variant in comparison to the healthy carrier father. Candidate genes were revealed by whole exome sequencing, and pathogenicity was predicted by different in silico tools. We found variants in NR1H2 and INHA associated with steroidogenesis, sex development, and reproduction. The identified variants were tested in cell models. Novel SF-1 and NR1H2 binding sites in the AR and INHA gene promoters were found. Transactivation studies showed that wild-type NR5A1/SF-1 regulates INHA and AR gene expression, while the NR5A1/SF-1 variant had decreased transcriptional activity. NR1H2 was found to regulate AR gene transcription; however, the NR1H2 variant showed normal activity. This study expands the NR5A1/SF-1 network of interacting partners, while not solving the exact interplay of different variants that might be involved in revealing the observed DSD phenotype. It also illustrates that understanding complex genetics in DSDs is challenging.

Parents' experiences in dealing with the development of adolescent Autistic Sexuality in West Java Province: A Phenomenological Study

Families who have autistic children may experience a burden in their lives. Little is known about how parents deal with their autistic children who are entering adolescence and are experiencing sexual development. What parents do to deal with the development of adolescent autistic sexuality can be found in qualitative research. The participants are parents with children who are autistic. The researcher contacted the parents and explained the informed consent; if parents agreed, they would sign the informed consent and then decide to place a time to interview the participant with the researcher, interviews with participants from January 2023-March 2023. This study aims to explore family experiences in dealing with sexuality development in adolescents with autism spectrum disorders. This phenomenological study collected data through in-depth interviews with semi-structured open-ended questions of seven child participants with autism spectrum disorders. Eleven themes constructed from this study are shy children when reminded not to hold their genitals, children are distracted when holding their genitals, children going through menstruation, children showing sexual behaviour by opening their pants, children holding their genitals, children hugging their mothers and seek attention, children stimulate themselves and others, children are easily aroused, children cannot distinguish boys and girls children like to clamp their genitals, And the child likes the prone position on the floor. Parents who feel that their child is currently facing the developmental phase of adolescent sexuality independently. They recommend that Parents provide adequate support, including appropriate education and open dialogue about the changes their child is experiencing.

Two phases of gonadal sex differentiation in zebrafish with ZZ/ZW sex determination system

Zebrafish sex chromosomes have been identified in the wild Nadia (NA) strain, and its sex determination belongs to the female-heterogametic ZZ/ZW system. Here, we investigate the correlation between ZZ/ZW sex chromosomes in the NA strain with sex-related factors, and sort out the complicated process of sex determination in zebrafish. Two phases exist during zebrafish sex differentiation. In the first phase, ZW gonads differentiate into juvenile ovary while ZZ gonads remain indifferent. In the second phase, ZW gonads either continue ovary development or undergo female-to-male transition, while ZZ gonads undergo direct male development. The W chromosome may contribute to the first phase while the abundance of germ cells and other factors may be involved in the second phase of sex differentiation in zebrafish.

The Transcriptome Characterization of the Hypothalamus and the Identification of Key Genes during Sexual Maturation in Goats.

Sexual maturation in goats is a dynamic process regulated precisely by the hypothalamic-pituitary-gonadal axis and is essential for reproduction. The hypothalamus plays a crucial role in this process and is the control center of the reproductive activity. It is significant to study the molecular mechanisms in the hypothalamus regulating sexual maturation in goats. We analyzed the serum hormone profiles and hypothalamic mRNA expression profiles of female goats during sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). The results indicated that from D1 to M6, serum hormone levels, including FSH, LH, progesterone, estradiol, IGF1, and leptin, exhibited an initial increase followed by a decline, peaking at M4. Furthermore, we identified a total of 508 differentially expressed genes in the hypothalamus, with a total of four distinct expression patterns. Nuclear receptor subfamily 1, group D, member 1 (NR1D1), glucagon-like peptide 1 receptor (GLP1R), and gonadotropin-releasing hormone 1 (GnRH-1) may contribute to hormone secretion, energy metabolism, and signal transduction during goat sexual maturation via circadian rhythm regulation, ECM receptor interactions, neuroactive ligand-receptor interactions, and Wnt signaling pathways. This investigation offers novel insights into the molecular mechanisms governing the hypothalamic regulation of goat sexual maturation.

Development of a comprehensive open access "molecules with androgenic activity resource (MAAR)" to facilitate risk assessment of chemicals.

The increasing prevalence of endocrine-disrupting chemicals (EDCs) and their potential adverse effects on human health underscore the necessity for robust tools to assess and manage associated risks. The androgen receptor (AR) is a critical component of the endocrine system, playing a pivotal role in mediating the biological effects of androgens, which are male sex hormones. Exposure to androgen-disrupting chemicals during critical periods of development, such as fetal development or puberty, may result in adverse effects on reproductive health, including altered sexual differentiation, impaired fertility, and an increased risk of reproductive disorders. Therefore, androgenic activity data is critical for chemical risk assessment. A large amount of androgenic data has been generated using various experimental protocols. Moreover, the data are reported in different formats and in diverse sources. To facilitate utilization of androgenic activity data in chemical risk assessment, the Molecules with Androgenic Activity Resource (MAAR) was developed. MAAR is the first open-access platform designed to streamline and enhance the risk assessment of chemicals with androgenic activity. MAAR's development involved the integration of diverse data sources, including data from public databases and mining literature, to establish a reliable and versatile repository. The platform employs a user-friendly interface, enabling efficient navigation and extraction of pertinent information. MAAR is poised to advance chemical risk assessment by offering unprecedented access to information crucial for evaluating the androgenic potential of a wide array of chemicals. The open-access nature of MAAR promotes transparency and collaboration, fostering a collective effort to address the challenges posed by androgenic EDCs.

BSPED audit of clinical standards for differences of sexual development (DSD)

BSPED audit of clinical standards for differences of sexual development (DSD)

Validation of a new short parent reported outcomes (PRO) questionnaire for boys with a condition affecting sex development

Validation of a new short parent reported outcomes (PRO) questionnaire for boys with a condition affecting sex development

Coming Out Queer: Sexual and Romantic Exploration and Identity Development of LGBQ+ College Students

LGBQ+ youth from conservative Christian families and/or communities face challenges developing positive understandings of their sexualities. Many view college as a more welcoming space that will allow them to conceptualize and enact their sexual identities in new and beneficial ways. Yet college campuses may support some aspects of LGBQ+ identity development at the expense of others. Through interviews with 26 LGBQ+ students from conservative Christian backgrounds, we show that the transition to college served as an opportunity to access supportive spaces that encouraged exploration and self-development and affirmed LGBQ+ identities, increasing self-esteem and well-being. However, many students still struggled to access sexual and romantic relationships, limiting opportunities to learn about themselves and their emerging desires. Our findings demonstrate how the interplay between communities of origin and destination conditions shape identity development in emerging adulthood and make clear the importance of sexual and romantic exploration to this process.

Acptp2,3 participates in the regulation of spore production, stress response, and pigments synthesis in Aspergillus cirstatus.

Aspergillus cristatus was a filamentous fungus that produced sexual spores under hypotonic stress and asexual spores under hypertonic stress. It could be useful for understanding filamentous fungi's sporulation mechanism. Previously, we conducted functional studies on Achog1, which regulated the hyperosmotic glycerol signaling (HOG) pathway and found that SI65_02513 was significantly downregulated in the transcriptomics data of ΔAchog1 knockout strain. This gene was located at multiple locations in the HOG pathway, indicating that it might play an important role in the HOG pathway of A. cristatus. Furthermore, the function of this gene had not been identified in Aspergillus fungi, necessitating further investigation. This gene's conserved domain study revealed that it has the same protein tyrosine phosphatases (PTPs) functional domain as Saccharomyces cerevisiae, hence SI65_02513 was named Acptp2,3. The function of this gene was mostly validated using gene knockout and gene complementation approaches. Knockout strains exhibited sexual and asexual development, as well as pigments synthesis. Morphological observations of the knockout strain were carried out under several stress conditions (osmotic stress, oxidative stress, Congo Red, and sodium dodecyl sulfate (SDS). Real-time fluorescence polymerase chain reaction (PCR) identified the expression of genes involved in sporulation, stress response, and pigments synthesis. The deletion of Acptp2,3 reduced sexual and asexual spore production by 4.4 and 4.6 times, demonstrating that Acptp2,3 positively regulated the sporulation of A. cristatus. The sensitivity tests to osmotic stress revealed that ΔAcptp2,3 strains did not respond to sorbitol-induced osmotic stress. However, ΔAcptp2.3 strains grew considerably slower than the wild type in high concentration sucrose medium. The ΔAcptp2,3 strains grew slower than the wild type on media containing hydrogen peroxide, Congo red, and SDS. These findings showed that Acptp2,3 favorably controlled osmotic stress, oxidative stress, and cell wall-damaging chemical stress in A. cristatus. Deleting Acptp2,3 resulted in a deeper colony color, demonstrating that Apctp2,3 regulated pigment synthesis in A. cistatus. The expression levels of numerous stress-and pigments-related genes matched the phenotypic data. According to our findings, Acptp2,3 played an important role in the regulation of sporulation, stress response, and pigments synthesis in A. cristatus. This was the first study on the function of PTPs in Aspergillus fungi.

Steroidogenic differentiation of human amniotic membrane-derived mesenchymal stem cells into a progesterone-/androgen-producing cell lineage by SF-1 and an estrogen-producing cell lineage by WT1-KTS.

Sex steroid hormones, primarily synthesized by gonadal somatic cells, are pivotal for sexual development and reproduction. Mice studies have shown that two transcription factors, steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1), are involved in gonadal development. However, their role in human gonadal somatic differentiation remains unclear. We therefore aimed to investigate the roles of SF-1 and WT1 in human gonadal steroidogenic cell differentiation. Using a transient lentivirus-mediated gene expression system, we assessed the effects of SF-1 and WT1 expression on the steroidogenic potential of human amniotic membrane-derived mesenchymal stem cells (hAmMSCs). SF-1 and WT1-KTS, a splice variant of WT1, played distinct roles in human steroidogenic differentiation of hAmMSCs. SF-1 induced hAmMSC differentiation into progesterone- and androgen-producing cell lineages, whereas WT1-KTS promoted hAmMSC differentiation into estrogen-producing cell lineages. Our findings revealed that SF-1 and WT1-KTS play important roles in human gonadal steroidogenic cell differentiation, especially during ovarian development. These findings may pave the way for future studies on human ovarian differentiation and development.

Tunable cell differentiation via reprogrammed mating-type switching

This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway. This strategy provides a versatile framework for producing and fine-tuning functionally heterogeneous yet isogenic yeast consortia, furthering the advancement of microbial consortia cooperativity and offering additional avenues for biotechnological applications.