Prepubertal Males Research Articles

Pubertal- and stress-dependent changes in cellular activation and expression of excitatory amino acid receptor subunits in the paraventricular nucleus of the hypothalamus in male and female rats.

Pubertal maturation is marked by significant changes in stress-induced hormonal responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis, with prepubertal male and female rats often exhibiting greater HPA reactivity compared to adult males and females. Though the implications of these changes are unclear, elevated stress responsiveness might contribute to the stress-related vulnerabilities often associated with puberty. The current experiments sought to determine whether differences in cellular activation, as measured by FOS immunohistochemistry, or excitatory ionotropic glutamate receptor subunit expression, as measured by qRT-PCR, in the paraventricular nucleus (PVN) were associated with these noted pubertal shifts in stress reactivity in male and female rats. As the PVN is the key nucleus responsible for activating the hormonal stress response, we predicted greater cellular activation and higher expression levels of glutamate receptor subunits in the PVN of prepubertal males and females compared to their adult counterparts. Our FOS data revealed that while prepubertal males showed greater stress-induced activation in the PVN than adult males, prepubertal females showed less activation than adult females. Moreover, many of the NMDA, AMPA, and kainate receptor subunits measured, including Grin1, Grin2b, Gria1, Gria2, Grik1, and Grik2, had higher expression levels in adults, particularly in males. Though not supporting our initial predictions, these data do indicate that age and stress influence the activation of the PVN and the expression of glutamate receptor subunits important in its function. These data also suggest that the effects of age and stress are different in males and females. Though still far from a clear understanding of what mechanism(s) mediate pubertal shift in stress reactivity, these data add to our growing understanding of how age, stress, and sex influence HPA function.

Associations of co-exposure to polycyclic aromatic hydrocarbons and heavy metals with sex steroid hormones among children aged 6-19 years.

Introduction Polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are endocrine-disrupting chemicals (EDCs) that may have a combined effect on sex hormone levels in children. This study investigated the correlations between co-exposure to PAHs and HMs and levels of sex steroid hormones in children. Methods We employed the data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016, including 1,167 participants aged 6-19 years. Sex hormone indicators include testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), free androgen index (FAI), and the TT/E2 ratio. Weighted multivariate linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze the associations between co-exposure to PAHs and HMs and sex steroid hormone levels. Results Co-exposure to PAHs and HMs was associated with a 16.2% reduction [95%CI (-0.321, -0.004)] in SHBG level among prepubertal males and a 16% reduction [95%CI (-0.30, -0.03)] in E2 level among pubertal males by the weighted quantile sum (WQS) regression, and cadmium (Cd) and mercury (Hg) contributed the highest weight respectively. In the Bayesian kernel machine regression (BKMR) model, co-exposure to PAHs and HMs was positively associated with TT/ E2 in pubertal males and negatively correlated with FAI in pubertal females, and 1-hydroxypyrene (1-PYR) and Cd were the most important components respectively. Conclusions Co-exposure to PAHs and HMs was associated with sex hormone levels in children. These findings highlight the necessity for preventing the effects of these chemicals on sex hormones.

P-344 Systematic review of the gonadotoxicity and risk of infertility of soft tissue sarcoma chemotherapies in pre- and postpubertal females and males

Abstract Study question What is the gonadotoxicity of soft tissue sarcoma chemotherapies to better counsel females and males about the risk of infertility? Summary answer Limited data about the gonadotoxicity indicate a rather high risk with an average suspected infertility in females of 71% and in males of 54%. What is known already There is increasing awareness of the need to counsel young female and male cancer patients about the gonadotoxicity of chemotherapies and the risk of infertility. In addition, fertility preservation measures are offered in most countries. However, our knowledge of the gonadotoxicity of most cancer diseases and chemotherapies is still limited making it difficult to indicate fertility preservation measures. Soft tissue and mesothelial cancer are such a types of cancer for which data is very poor. The gonadotoxicity and risk of infertility of soft tissue and mesothelial cancer has not yet been systematically reviewed. Study design, size, duration This review is part of the FertiTOX project (www.fertitox.com) which aims to close the gap of data regarding gonadotoxicity of cancer therapies to enable more accurate counselling regarding fertility preservation. A systematic literature search considering papers on gonadotoxicity of treatment of soft tissue sarcoma and mesothelial cancer was performed. A total of 2801 records were identified for abstract screening. The review was performed from December 2022 until October 2023. Participants/materials, setting, methods A literature search of papers published in the databases of MEDLINE, Embase, and Cochrane Library since 2000 was performed. Only females and males without metastases or recurrent disease were considered. Due to limited infertility data the outcome parameter “Suspected infertility” was defined based on reported low ovarian reserve parameters, low inhibin B, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia or oligozoospermia. Main results and the role of chance The database search yielded a total of 2801 abstracts, 136 of which were included in the full-text analysis. Of these, 7 studies, each on soft tissue sarcomas, could be included in the review. Studies on mesothelial cancer could not be identified. Two of the 7 soft tissue sarcoma studies were retrospective and 5 were prospective. Of the 7 studies, 3 provided data on women, 3 on men and 1 on both genders. A total of 28 women and 50 men, a total of 78, were included. The pubertal status could not be determined for all patients. Suspected infertility was found in 20 of 28 (71.4%, range 0-100%) of females (4 studies) and in 27 of 50 (54%, range 34.8-100%) of males (4 studies) soft tissue sarcoma patients. Limitations, reasons for caution The weakness is the inclusion of prepubertal and pubertal females and males, and the unknown pubertal status in some cases. A further weakness is the heterogenous spectrum of infertility markers and the limited number of studies which required to define for the analysis the rather vague outcome parameter “suspected infertility”. Wider implications of the findings Our data suggest a high risk of infertility due to chemotherapies in soft tissue sarcomas. This appears to be more pronounced in females than in males, although precise information cannot be given due to limited data. However, even though the study emphasizes the importance to consider fertility preservation measures. Trial registration number PROSPERO (Registry number CRD42023385402)

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.

Patient Characteristics and Postoperative Outcomes of Surgically Treated Inferior Pole Patellar Sleeve Fractures.

Despite representing over half of all pediatric patella fractures, inferior pole patellar sleeve fractures (PSFs) are a relatively uncommon pediatric injury. As a result, existing literature on PSFs is limited to case reports and small case series. The purpose of this study was to evaluate the radiographic and clinical characteristics of operatively treated PSFs as well as outcomes following surgical management. A retrospective review of all inferior pole PSFs requiring surgery from 2007 to 2023 was performed at a single urban tertiary care children's hospital. Cases were identified using diagnostic and billing codes. Patient demographics, injury characteristics, surgical techniques, and postoperative rehabilitation practices were recorded. Regional skeletal maturity, fracture characteristics, and postreduction patellar height were recorded. Postoperative complications were recorded and categorized using the modified Clavien-Dindo Classification System (CDS). Thirty-eight inferior pole PSFs were identified meeting study criteria. The majority of patients were male (86.8%), and the mean age at injury was 11.0 years (range: 7.2 to 15.0). Mean BMI was 21.1. Radiographically, the majority of patients were Epiphyseal Fusion Stage 0 (nonunion), with a median postreduction Caton-Deschamps index (CDI) of 1.2 (IQR: 1.1 to 1.3). These fractures were predominantly treated with suture-based fixation (84%). Postoperative immobilization varied within the cohort, and the initiation of knee ROM was permitted at a median of 3.5 (IQR: 2.0 to 4.6) weeks. All patients regained full range of motion and straight leg raise without extensor lag, and return-to-sport was achieved by a median of 17.6 weeks (IQR: 12.8 to 30.3). Complications occurred in 10 (26.3%) patients, with 3 (7.9%) requiring a return to the OR (CDS Grade III). Inferior pole PSFs appear to occur most commonly among prepubertal males of normal BMI and normal patellar height. Despite variable rehabilitation protocols, operative management resulted in restoration of extensor mechanism function. Eight percent of patients experienced complications requiring unplanned surgery. This large series improves our understanding of the epidemiology, injury characteristics, and postoperative outcomes of an operatively treated cohort of a rare injury pattern. Level IV.

Interplay of hormones and metabolite excretion with fern pattern prove saliva as a potent indicator of male reproductive status in Kangayam breed cattle.

Kangayam cattle are one of the drought breeds in India with distinct attributes. Agricultural transformation has led to a decline in many pure-breed indigenous cattle, including the Kangayam breed. Hence, a study on the reproductive physiology of male Kangayam breed cattle is necessary to disentangle problems in the area of livestock improvement. In this study, we investigated the relationship between serum hormones and bio-constituents and ascertained the potential of saliva as an indicator of the reproductive status of Kangayam cattle (Bos indicus). The present study confirms that cholesterol was higher in intact males and lower in prepubertal and castrated males. Testosterone levels were also higher in intact males than in castrated or prepubertal males. Hence, it can be inferred that high cholesterol levels contribute to active derivatization of testosterone in intact males. In contrast, reduced cholesterol availability leads to decreased testosterone synthesis in castrated and prepubertal males. Furthermore, it is reasonable to speculate that testosterone could have influenced salivary fern patterns in intact males, and thus, fern-like crystallization in the saliva was apparent. The unique salivary compounds identified through GC-MS across various reproductive statuses of Kangayam males may advertise their physiological status to conspecifics. In addition, the presence of odorant-binding protein(OBP) in saliva further supports its role in olfactory communication. This study attested to a posssible interlink between gonadal status and serum biochemical profiles. The salivary fern pattern revealed in this study can be used as a predictive tool, and the presence of putative volatiles and OBP adds evidence to the role of saliva in chemical communication.

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey.

Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue? Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding. For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established. A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022. Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis. Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm3 with the remainder preserving fragments sized 6-20 mm3. Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres. While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre. Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients. K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation-Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB_SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G., N.N., S.S., C.L.M., A.M.M.v.P., C.E., R.T.M., K.D., M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests. N/A.

Echogenicity of different structures of the scrotal bag in rams: effect of age, injuries and sexual activity

The purpose of this research was to characterise the echogenicity of the different structures within the scrotal bag in rams. Three studies that included 43 rams were conducted. Ultrasound sections (US) were made with the Mindray® equipment. It was found that pubertal males showed greater echogenicity (P<0.05) in testes and the pampiniform plexus, whereas prepubertal males (P<0.05) - in the epididymis and in the right pampiniform plexus. Rams in mating showed the highest echogenicity values (P<0.05). In non-mating animals, the highest values were found in the epididymis (P<0.05). Rams with injuries presented higher echogenicity in testes (P<0.05). In pampiniform plexuses, males without injuries demonstrated the highest values (P<0.05). A high and positive correlation (P<0.0001) was found between the evaluated variables, specifically the right cranial longitudinal (RCL), right proximal transverse (RPT), right medial transverse (RMT), right distal transverse (RDT) measures. Echotexture in rams was affected by age, presence of injuries and sexual activity. In addition, the high correlation suggests that the evaluation of testicular health in rams could be carried out only with several US.

The influence of maturation and sex on intracranial blood velocities during exercise in children.

Cerebral blood velocity (CBv) increases in response to moderate exercise in humans, but the magnitude of change is smaller in children compared with postpubertal adolescents and adults. Whether sex differences exist in the anterior or posterior CBv response to exercise across pubertal development remains to be determined. We assessed middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) blood velocity via transcranial Doppler in 38 prepubertal (18 males) and 48 postpubertal (23 males) with cerebrovascular and cardiorespiratory measures compared at baseline and ventilatory threshold. At baseline, MCAv was higher in both sexes pre- versus postpuberty. Females demonstrated a greater MCAv (P < 0.001) than their male counterparts (prepubertal females; 78 ± 11 cm·s-1 vs. prepubertal males; 72 ± 8 cm·s-1, and postpubertal females; 68 ± 10 cm·s-1 vs. postpubertal males; 62 ± 7 cm·s-1). During exercise, MCAv remained higher in postpubertal females versus males (81 ± 15 cm·s-1 vs. 73 ± 11 cm·s-1), but there were no differences in prepuberty. The relative increase in PCAv was greater in post- versus prepubertal females (51 ± 9 cm·s-1 vs. 45 ± 11 cm·s-1; P = 0.032) but was similar in males and females. Our findings suggest that biological sex alters anterior cerebral blood velocities at rest in both pre- and postpubertal youth, but the response to submaximal exercise is only influenced by sex postpuberty.NEW & NOTEWORTHY Cerebral blood velocity (CBv) in the anterior circulation was higher in females compared with males irrespective of maturational stage, but not in the posterior circulation. In response to exercise, females demonstrated a greater CBv compared with males, especially post-peak height velocity (post-PHV) where the CBv response to exercise was more pronounced. Our findings suggest that both CBv at rest and in response to acute submaximal exercise are altered by biological sex in a maturity-dependent manner.

Degrees of Testicular Atrophy Following Orchidopexy for Testicular Torsion.

Introduction Testicular torsion is an urological emergency. It is a time-sensitive condition in which twisting of the spermatic cord and testicular blood supply occurs, causing acute onset severe scrotal pain. The incidence of testicular torsion is highest amongst prepubertal males; however, it can occur at any age. Every hour that passes from the onset of symptoms has been shown to decrease the salvageability rate of the torted testis. Another significant factor that impacts testicular salvage is the degree of torsion. Prompt surgical exploration of the scrotum and orchidopexy, if the testis is salvageable, is the mainstay of treatment. A major sequela following orchidopexy for torsion is the decrease in testicular volume. The aim of this study is to assess testicular volume loss post orchidopexy in patients who presented with testicular torsion, as well as to identify the significance of the degree of rotation and duration of torsion in post-fixation volume loss. Methods This is a retrospective study in which all patients who underwent scrotal exploration for a primary diagnosis of testicular torsion between June 1, 2016, to January 15, 2023, were reviewed. The information obtained included the patients' demographics such as age, duration of symptoms, and laterality. Ultrasound images were reviewed for pre- and postoperative findings which included confirmation of testicular torsion as well as testicular volume measurements. Patients were excluded if they underwent an orchidectomy, had a diagnosis other than testicular torsion once scrotal exploration was done, or did not perform a follow-up scrotal ultrasound. Additionally, patients who underwent an orchidopexy for undescended testis earlier in life were also excluded. For statistical analysis purposes, degrees of testicular torsion and time to surgery were classified into mild, moderate, and severe. Results A total of 109 patient records were reviewed within the specific time frame. Of these, 47 patients were excluded as per the exclusion criteria mentioned previously, which gave us a sample size of 62 patients. Our findings showed that increasing severity of the degree of torsion as well as the time for surgery have statistically significant (p-value <0.05) effects on postoperative testicular volume loss. However, it was noted that time to surgery has a more pronounced effect on the mean volume loss than the degree of torsion. Moreover, the analysis also showed that, on average, with every additional hour from the onset of symptoms to surgery, the approximate volume loss is 0.15 ml. However, once time exceeds the 4.5-hour mark, the mean volume loss is 0.4 ml for each additional hour. Conclusion The current study indicates that earlier surgical intervention and correction of torsion are associated with enhanced preservation of postoperative testicular volume. Both the degree of torsion and time to surgery influence mean volume loss; however, time to surgery has a greater impact on the mean volume loss. These results highlight the importance of early diagnosis and intervention in cases of testicular torsion to minimize the risk of long-term testicular volume loss.

Oncofertility: technical challenges in immature testicular tissue banking

The gonadotoxicity of cancer therapy ranges from severe to mild effects on spermatogenesis, structural, functional, and genetic integrity of spermatozoa. However, these effects are even more pronounced in prepubertal males due to the susceptibility of the prepubertal testis to cytotoxic therapy. The proliferating germ cells in the prepubertal testis are mitotic in nature, thereby becoming a target for anticancer agents. Immature testicular tissue (ITT) cryopreservation is offered as the only fertility preservation (FP) strategy for prepubertal males facing gonadotoxic risk, though it is still experimental in nature. Multiple cryopreservation protocols have been developed to ensure safe and efficacious storage of the tissue and to enable maximum recovery of germ cells during thawing. The thawed tissue can then be used for fertility restoration by either in vitro spermatogenesis or transplantation to reinitiate spermatogenesis and thereby result in the production of mature spermatozoa. However, there are many challenges to overcome to successfully offer this procedure as an established one. This mini-review gives an overview of the progress in ITT cryopreservation and fertility restoration procedures, along with the other challenges.

Leptin Concentrations Determine the Association between High-Sensitivity C-Reactive Protein Levels and Body Mass Index in Prepubertal Children.

Obesity is associated with the presence of low-grade inflammation even during childhood. The dysregulation in the secretion of adipokines, such as leptin, which occurs in obesity states, could be associated with an increase in inflammatory factors already at an early age. In this cross-sectional study, we aimed to investigate the role of leptin levels in the association between body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) in healthy schoolchildren. Leptin and hs-CRP levels were analyzed in two pediatric cohorts comprising 684 prepubertal children and 763 adolescents. hs-CRP concentrations correlated significantly with BMI and leptin levels in prepubertal males and females as well as in adolescents. However, after adjusting for leptin concentration, no significant correlation was observed between hs-CRP and BMI in prepubertal children, while the correlations remained significant in adolescents. The same differences were observed when analyzed BMI according to hs-CRP tertile after adjusting for leptin; mean BMI was not significantly different between hs-CRP tertile in prepubertal children but was significantly different in adolescents. In conclusion, the fact that leptin concentrations determine the association of BMI with hs-CRP levels in prepubertal children, but not in adolescents, suggests a role for leptin in low-grade inflammation at early ages, while other factors seem to contribute to hs-CRP levels later in life.

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p=.0278) and low INHB serum levels (p=.0130) were recorded after CT-HSCT, especially after myeloablative conditioning. The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.

Reproductive response of crossbred Bos taurus x Bos indicus cows to biostimulation by pre-pubertal and pubertal teasers.

Although, the beneficial effect of biostimulation on reproduction has been reported, the influence of selectivity and social factors on the response to biostimulation has not received sufficient research attention in both, Bos indicus and Bos indicus influenced cattle. Moreover, "green and cheap" strategies to improve cattle reproduction are currently in demand while Bos indicus influenced cattle with inferior reproductive performance and farmers with economic limitations are common in tropical zones. Hence, to assess the reproductive response of crossbred taurus x indicus cows to biostimulation by pre-pubertal (PPM) or pubertal (PM) teasers males, two trials of two years each were conducted. Trial 1 n=187 cows (Year 1:85 cows exposed to PPM and Year 2:102 cows exposed to PM). Trial 2 n=196 cows (Year 1:101 cows exposed to PPM and Year 2:95 cows exposed to PM). The effect of exposing cows to PPM and PM on the intervals calving to first service (ICFS), calving to conception (ICC) and economic cost of days open (ECDO) was analyzed using Kruskal-Wallis ANOVA and the effect of exposing cows to PPM and to PM on reproductive status at 90d (RS90) and proportion of cows requiring hormonal protocols (PRH) was compared using χ2 analysis. Both, ICFS and ICC were shorter (P<0.0001) for PM-exposed females (96.12±4.1 and 110.93±2.9 d; respectively) than for those PPM-exposed (134.41±3.3 and 135.64±2.4 d; respectively). With RS90, more (P<0.0001) PM-exposed cows (50.7%) were pregnant than PPM-exposed cows (16.1%). The PRH was greater (P<0.0001) in PPM-exposed cows (79.0 %) compared to PM-exposed (27.9%). The ECDO was less (P<0.0001) in PM-exposed cows (US$ 142.9±3.8) than PPM-exposed (US$ 176.3±2.9). In conclusion, cows exposed to PM had shorter ICFS and ICC than cows exposed to PPM. More cows exposed to PM were pregnant after 90d and PRH was less than cows exposed to PPM. Cows exposed to PM had a reduced ECDO than those exposed to PPM.

Diagnostic performance of different anthropometric indices among Iranian adolescents for intima media thickness in early adulthood: A prospective study and literature review.

There is debate regarding which anthropometric indices is the most appropriate predictor of cardiovascular disease (CVD) among adolescents. The purpose of this study was to investigate the association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) in adolescents with high carotid intima-media thickness (cIMT) in early adulthood, as the surrogate marker of CVD in a cohort study. A total of 875 Iranian adolescents (female = 421) aged 10-17 years old were entered the study. The cIMT was measured in early adulthood (20-38 years old) after 18.2 (median) years of follow-up and defined as > 90th percentile for sex and age groups. The gender specific association between a 1-SD increase in each anthropometric measures with high cIMT was examined using multivariate logistic regression analysis adjusted for age, smoking, family history of CVD, systolic blood pressure, total cholesterol, and fasting blood sugar. In the multivariable analysis, the interaction between sex and age groups with anthropometric measures were significant (all p-values < 0.05). Among males, all anthropometric measures including BMI, WC, WHR, and WHtR were associated with high cIMT; the corresponding odds ratios were 1.43 (1.05-1.94), 1.63 (1.22-2.19), 1.33 (1.03-1.71), and 1.41 (1.07-1.87), respectively. However, after considering the related adulthood anthropometric measurements, the association remained significant for WC 1.48 (1.04-2.10) and WHR [1.28 (0.99-1.66), P = 0.06]. Moreover, among early adolescent boys aged 10-14 years, all of the anthropometric measures were significantly associated with high cIMT in the multivariate analysis that included the related adulthood anthropometric measures. The area under the curve (AUC) for the anthropometric measurements among males ranged from 0.576 for WHtR up to 0.632 for WC, without any superiority between them. Among females, only in linear regression analysis, a significant association were found between the higher value of WC and WHtR with cIMT measurement in adulthood; however, the risk reached to null after considering adult anthropometric measures. General and central obesity measures were significantly associated with high cIMT only among Iranian male adolescents, the relationship that were more prominent among pre-pubertal males.

Engineered Immature Testicular Tissue by Electrospun Mats for Prepubertal Fertility Preservation in a Bioluminescence Imaging Transgenic Mouse Model.

Prepubertal boys with cancer may suffer from reduced fertility and maturity following gonadotoxic chemoradiotherapy. Thus, a viable method of immature testicular tissue (ITT) preservation is required in this cohort. In this study, we used poly-L-lactic acid electrospun scaffolds with two levels of fineness to support the development of ITT transplanted from transgenic donors to wild-type recipient mice. The purpose of this study was to evaluate the potential of ITT transplantation and spermatogenesis after using the two scaffolds, employing bioluminescence imaging for evaluation. The results suggest that ITT from 4-week-old mice possessed the most potential in spermatogenesis on the 70th day, together with the fine electrospun scaffolds. Moreover, bioluminescent imaging intensity was observed in recipient mice for up to 107 days, approximately six times more than the coarse electrospun scaffold and the control group. This occurs since the fine scaffold is more akin to the microenvironment of native testicular tissue as it reduces stiffness resulting from micronization and body fluid infiltration. The thermal analysis also exhibited recrystallization during the biodegradation process, which can lead to a more stable microenvironment. Overall, these findings present the prospect of fertility preservation in prepubertal males and could serve as a framework for future applications.

Maternal Education Potentially Moderates the MAOA uVNTR Effects on Externalizing Behavior in Black South African Children

Interactions between the MAOA uVNTR and rearing environment are suggested to influence the developmental manifestations of childhood internalizing and externalizing behavior. However, few studies in the MAOA literature have included continental African children, or focused on non-clinical samples. We explored the main and interactive effects of the MAOA uVNTR (high and low activity alleles) in Black South African male (n = 478) and female (n = 540) children who were part of the longitudinal Birth to Twenty Plus cohort. Historical data on birth weight, gestational age at delivery, socioeconomic status, and maternal education were combined with genotypic information and analyzed using regression modeling. We found no significant main effects for the MAOA uVNTR on childhood behavior in either sex. A significant interaction (p = .04) was identified between MAOA and maternal education, suggesting that externalizing behavior in boys carrying a low activity MAOA allele varied in direct proportion to the education levels of their mothers. However, the model fit failed to reach significance, possibly due to our inclusion of only non-clinical pre-pubertal males. No significant interactions were detected for female children. Our findings lend tentative credibility to the Environmental Sensitivity metaframework, which suggests that MAOA is an important plasticity factor in childhood development.

National Ovarian and Testicular Tissue Transport and Cryopreservation Service (NOTTCS)

Background: Recognised female fertility preservation strategies include oocyte and embryo cryopreservation. Ovarian tissue cryopreservation is no longer experimental, and the only option for children and pre-pubertal girls. Although testicular cryopreservation remains experimental for boys, it has the potential to evolve and provide a realistic opportunity for fertility in the future. The RWH/MIVF fertility preservation service has been preserving ovarian tissue since 1995. This service has been available to children, adolescent young adults (AYA) and adults about to receive gonadotoxic treatment for malignant and non-malignant conditions. In 2013, this service was extended to freezing testicular tissue for pre-pubertal and peri-pubertal males. Until 2019 these fertility preservation options have only been available to those undergoing procedures at Melbourne metropolitan hospitals. Young cancer patients seeking fertility preservation in regional or interstate areas, did not have this opportunity due to lack of access and resources. One approach to increasing patient access to Gonadal Tissue Cryopreservation (GTC), was to establish a national tissue retrieval and transport service. Aim: This paper describes the uptake of a GTC transport program at RWH, allowing rural and interstate oncology referral for transport, processing and storage of gonadal tissue in an acknowledged centre of excellence. Method: An information/education/instruction resource package was developed for fertility units Australia-wide, supported by a centralised GTC program coordinator. Referrals are fast tracked to eliminate any delay in treatment. Gonadal tissue is harvested at the referring hospital and transported to RWH for cryopreservation and storage, following methods established in other countries with a centralised service 1 – 3 . Results: To date, 40 ovarian and testicular tissue has been transported from all Australian states, and Northern Territory to RWH, including semen transported from a regional hospital where no fertility service was available. This service was made possible, and free of charge to those patients 13–30 yo with a cancer diagnosis, through a generous donation by Sony Foundation. Conclusion: Provision of a comprehensive fertility preservation service, including GTC, for young people, was not widely available until 2019. Gonadal tissue transport facilitates engagement and upskilling in oncofertility with extensive support from a centre of excellence, allowing expansion of patient and provider access to best-practice fertility preservation options, regardless of their geographic location and socio-economic status.

Factors Associated With Fertility Preservation in a Pediatric, Adolescent and Young Adult Population.

To determine the patient characteristics associated with pursuing fertility preservation (FP) before gonadotoxic therapy in a pediatric, adolescent and young adult patient population. This is a retrospective cohort study of patient data at Cincinnati Children's Hospital Medical Center. Demographics, clinical diagnoses, and treatment characteristics were compared between participants that selected FP versus those that declined. Variables were analyzed separately for males and females by logistic regression. Patients with a hematologic cancer were less likely to be eligible for preservation: 53.9% of ineligible males, P <0.001, and 51.8% of ineligible females, P <0.0001. Among patients who were candidates for FP, those receiving high-risk therapy were more likely to elect for FP (65.3% males, P <0.0001, and 87.5% of females, P <0.0001). Pubertal males were more likely to undergo preservation than prepubertal males (70.5% vs. 29.5%, P <0.0001; however, this trend was not demonstrated among female patients. In both males and females, race, ethnicity, religion, primary language, and insurance status were not shown to be statistically significant factors in predicting utilization of FP. Risk of infertility, type of cancer, and developmental status influenced decisions on pursuing FP in pediatric, adolescent and young adult patients facing iatrogenic infertility.

Pubertal stage, sex and behaviour in neurodevelopmental disorders versus typical development: a cross-sectional study

ObjectiveTo determine the association between pubertal stage, sex and behavioural profile across and within neurodevelopmental disorders (NDDs) compared with typically developing (TD) youth.MethodsThis was a cross-sectional study from the Province...