ResearchPad - sexual-differentiation Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Effect of aging and body characteristics on facial sexual dimorphism in the Caucasian Population]]> The aim of this study was to quantify gender-specific facial characteristics in younger and older adults and to determine how aging and body characteristics, such as height and body-mass index (BMI), influence facial sexual dimorphism.MethodsThe cohort study included 90 younger adults of Caucasian origin (average age of 45 females 23.2 ± 1.9 and 45 males 23.7 ± 2.4 years) and 90 older adults (average age of 49 females 78.1 ± 8.1 and 41 males 74.5 ± 7.7 years). Three-dimensional facial scans were performed with an Artec MHT 3D scanner. The data were analyzed using the software package Rapidform®. The parameters to evaluate facial symmetry, height, width, profile, facial shape, nose, eyes and mouth characteristics were determined based on 39 facial landmarks. Student’s t-test was used to calculate the statistical differences between the genders in the younger and older adults and a multiple-linear-regression analysis was used to evaluate the impact of gender, age, body-mass index and body height.ResultsWe found that the female faces were more symmetrical than the male faces, and this was statistically significant in the older adults. The female facial shape was more rounded and their faces were smaller, after normalizing for body size. The males had wider mouths, longer upper lips, larger noses and more prominent lower foreheads. Surprisingly, we found that all the gender-dependent characteristics were even more pronounced in the older adults. Increased facial asymmetry, decreased facial convexity, increased forehead angle, narrower vermilions and longer inter-eye distances occurred in both genders during aging. An increased BMI was associated with wider faces, more concave facial profiles and wider noses, while greater body height correlated with increased facial heights and wider mouths.ConclusionFacial sexual dimorphism was confirmed by multiple parameters in our study, while the differences between the genders were more pronounced in the older adults. ]]> <![CDATA[SUN-083 Screening of Vitamin D and Calcium Concentrations in Neonates of Mothers at High Risk of Vitamin D Deficiency]]> Objective: The aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency (maternal 25OHD < 25 nmol/L or unknown vitamin D concentrations and risk factors for vitamin D deficiency) and critically analyse whether their measurements contributes to the management of these neonates.

Methods: Serum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed. 25OHD concentrations were reported for all while both the corrected calcium concentrations and vitamin D concentrations were available for 569 samples.

Results: There was little or no evidence of association between neonatal 25OHD concentrations and gender, gestational age or birth weight. There was a high prevalence of vitamin D insufficiency (27.6%, 30–50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between serum calcium and 25OHD concentrations. Only 7 neonates out of 569 (1.2%) had calcium levels in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 hours after birth. We calculated the reference interval for corrected calcium from our data of venous samples in first 24 hours and the upper limit was significantly higher (2.38–3.04 mmol/L) than the standard reference range used.

Conclusion: Vitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial impost on staff and financial burden on the health care system. 25OHD deficiency is corrected relatively easily in neonates with supplementation and vitamin D supplementation of neonates from birth without routine screening appears to offer better value of care. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates is higher and the paediatric reference range should be reconsidered.

<![CDATA[SUN-095 Understanding and Communication Around DSD According to the Mothers and Patients’ Perspectives]]> Communication around DSD is complex. It involves diagnosis and treatment aspects and is influenced by the psychological status of the individuals and the cultural context. An adequate understanding by patients and relatives is essential for approach of DSD. Objetive: To evaluate the DSD care setting in three Brazilian tertiary centers in order to identify the barriers to an adequate understanding and an optimal communication. Methods: A guide with 69 questions, assessing the level of knowledge, the main doubts and difficulties around DSD was developed and guided individual interviews with 100 mothers and 53 adult patients with DSD. The main doubts were clarified and a self-assessment was requested to them before and after the interview on a scale from 0 to 10. Results: Mothers and patients mean age were, respectevily, 35.2 and 36.5 years. Both of them had a satisfactory educational level. Although 48% (p<0.01) of mothers and 68% (p:0.02) of patients were satisfied/very satisfied about their knowledge related to the DSD, 78% and 58%, respectively, of them still had doubts. The doubts were related to diagnosis, karyotype, medications, appearance of genitalia, surgery, sexual activity, fertility, genetic counseling, consequences of the condition and treatment on general health and condition influence on the child’s behavior and personality The unsatisfied mothers cited as barriers to an optimal understanding the complexity of the conditions, the difficult terms and the psychological stress at diagnosis. Patients also cited as barriers the absence of dialogue about the condition at home and some of them chose not to know. About 55% of mothers and 62% of patients didn’t even know the name of the condition; but positively 88% of them knew the necessary treatment. Regarding communication, 68% of mothers and 89% of patients didn’t feel comfortable talking to people about the DSD condition and around 68% of them underwent negative comments. Although 73% of patients would prefer to be first informed about their condition at childhood, 29% of mothers think that childhood is the best age for it. Among mothers and patients, the most and least appropriate term to name the DSD condition is, respectively, genital malformation and disease (p<0.01). Both of them have the stigma as the main concern. Conclusion: Even in a tertiary center with a multidisciplinary team, the mothers and patient’s knowledge about DSD conditions is scarce. The proper choice of the term to refer to DSD conditions should consider the families and patients perspectives. Communication about DSD is prejudiced by the lack of knowledge and the stigma suffered by these patients and families. Thus, due to complexity of this topic, continued educational action must be instituted as a strategy to modify this scenario.

<![CDATA[SUN-091 Change in Sex of Rearing in Individuals with Disorders of Sex Development]]> Introduction: Differences of Sex Development (DSDs) encompass variations in formation of internal or external sex characteristics. Historically, sex assignment in children with DSDs depended on phenotype, and gender was thought to be malleable. Attention in DSD has recently shifted toward reducing gender dysphoria and preserving fertility potential. Our multidisciplinary DSD clinic was formed in 2008 with these goals and includes specialists from Endocrinology, Gynecology, Urology, Psychology, Social Work, Genetics, and Chaplaincy.

Subjects: A chart review was done on all patients seen in our DSD clinic between April 2008 and June 2019 to determine rates of sex reassignment and gender dysphoria. Two hundred patients were seen: 23 were found to not have DSDs; 61 were 46,XX; 66 were 46,XY; 31 had a sex chromosome DSD; 5 had gonadal dysgenesis without known chromosome mosaicism; and 14 had syndromic genital atypia. Mean age of follow-up is 8.77 years.

Results: Only 2 patients underwent sex reassignment at our institution. One was assigned male at birth, but was found to be 46,XX with 21-hydroxylase deficiency and was reassigned female at 1 month of age. The second was assigned male at birth and was found to be 46,XY with an NR5A1 variant. Sex was reassigned female at two months of age. Two additional patients had a sex reassignment outside our institution. One was born abroad and assigned male at birth. The patient was found to be 46,XY with an NR5A1 variant, and was reassigned female. The second patient was assigned male at birth, but was found to be 46,XX with P450 oxidoreductase deficiency. The parents changed the sex of rearing to female at 19 months of age. To date, none has signs of gender dysphoria.

A total of three patients experienced gender dysphoria and underwent transition. The first had genital ambiguity with sex chromosome mosaicism in the gonads and was assigned female at birth. We held care conferences with the family and discussed the possibility of gender dysphoria. At age 3, the patient declared that he was male, and parents socially transitioned him at that time. Two were assigned female after receiving the diagnosis of 46,XX 21-hydroxylase deficiency. Both declared male gender identity later, one at 12.5 years of age, and one at 20.5 years of age.

Conclusion: Whereas our patient population is still relatively young, it is reassuring that the overall rate of gender dysphoria is low. The rate in patients with CAH is similar to previous reports in the literature. Careful attention to sex assignment in early childhood may reduce the rates of gender dysphoria in children with DSDs.

<![CDATA[SUN-100 Mice Lacking Paternally Expressed DLK1 Reach Puberty at a Lower Body Weight Than Littermate Controls]]> Body fat content along with a variety of genetic, environmental and psychosocial factors are responsible for the development and maintenance of reproductive function, especially in females. Epidemiologic studies indicate a relationship between increased body mass index and earlier puberty in girls. In contrast, a significant delay in puberty and menarche is seen in girls who are very physically active and have markedly diminished body fat. This link between reproduction and metabolism was reinforced with the recent report of loss-of-function mutations in the Delta-like homolog 1 (DLK1) gene in girls with central precocious puberty (CPP) and increased body fat. DLK1 is a paternally expressed gene located on chromosome 14q32.2 in a locus associated with Temple syndrome (TS), an imprinting disorder caused mainly by maternal parental disomy (mUPD). Dlk1 knockout mice display pre- and postnatal growth retardation, a phenotype that overlaps with human mUPD14. However, precocious puberty, a common finding associated with TS, was not carefully characterized in these mice. We used a Dlk1 deficient mouse model to determine the effects of Dlk1 on pubertal maturation. We confirmed by RT-qPCR that Dlk1 mRNA was undetectable in the mediobasal hypothalamus, where kisspeptin and other regulators of puberty are expressed, of Dlk+/p- mice (which inherited the mutant allele from their father) whereas it was present in Dlk+/+ mice. As reported previously, body weight was significantly lower in juvenile male and female Dlk+/p- mice, compared to wild-type littermate controls. Interestingly, mutant and control female mice achieved vaginal opening, a marker of puberty onset, at a similar age (Dlk+/p-: 29.8 ± 1.5 days, n=11 vs. Dlk+/+: 29.1 ± 0.7 days, n=15, p=0.6) despite a considerably lower body weight in the Dlk1 deficient mice at the time of vaginal opening (Dlk+/p-: 10.1 ± 0.8 g vs. Dlk+/+: 14.3 ± 0.3 g, p<0.0001). Similarly, in the Dlk+/p- males, preputial separation occurred at a lower body weight than in controls (Dlk+/p-: 12.4 ± 0.3 g, n=9 vs. Dlk+/+: 14.1 ± 0.2 g, n=19, p<0.0001). We hypothesize that the lack of Dlk1 at the hypothalamic level may be attenuating the effect of the low body weight on determining pubertal onset. These findings suggest that DLK1 is an important link between body weight and pubertal development in mice, as has been shown in humans.

<![CDATA[SUN-092 Effect of Pubertal Induction with Gonadotropins and GnRH Therapy in Male Hypogonadotropic Hypogonadism: Meta-Analysis]]> Background: The use of gonadotropins is a recent strategy for inducing puberty in adolescent males with hypogonadotropic hypogonadism (HH). Testosterone use has been discouraged in patients who desire to preserve fertility. Human chorionic gonadotropin (hCG) has been recommended for inducing puberty in HH; however, several clinicians administer hCG in combination with other gonadotropins. The benefits of using combination gonadotropin therapies (hCG+) over hCG monotherapy in pre-pubertal adolescent males with HH has not been clearly established. We performed a meta-analysis to assess the outcomes of hCG compared to hCG+ in terms of virilizing effects and testicular growth in peripubertal boys with HH.

Methods: We evaluated for heterogeneity among studies. We calculated pooled means for the post-treatment mean testicular volume (MTV), testosterone (T) level, and penile length for the hCG monotherapy and hCG+ treatment groups. We performed a meta-regression analysis to examine the contribution of various factors to post-treatment outcomes including baseline T level, age, treatment duration, and study quality.

Results: The meta-analysis included seven studies. All participants were prepubertal (age range: 13.3–25.9 years), with weighted mean treatment durations of 10.95 months for hCG monotherapy and 28.2 months for hCG. There was significant heterogeneity in baseline age (Q = 121.71; df = 1; P < 0.001) and T levels (Q = 436.74; df = 1; P < 0.001) between the two treatment groups. The hCG+ group had a larger post-treatment MTV, but it was not significantly different between the two groups (6.60 mL [95% CI, 3.18–10.02] for hCG monotherapy vs. 10.02 mL [95% CI, 8.30–11.75] for hCG+; P = 0.079). Post-treatment T levels differed significantly between the two groups (101.89 ng/dL [95% CI, 50.7–153.08] for hCG monotherapy vs. 424.10 ng/dL [95% CI, 304.59–543.62] for hCG+; P < 0.0001). A meta-regression analysis of post-treatment T levels showed that baseline age, baseline T level, and study grade did not contribute significantly to the difference between treatment groups. Treatment duration explained 3.04% of the difference between the two groups (P < 0.0001). After adjusting for treatment duration, the post-treatment T level remained significantly higher in the hCG+ group compared to the hCG monotherapy group. The hCG+ was also associated with better outcomes for post-treatment penile length, although these findings relied on data from only three studies.

Conclusion: Our study indicates that hCG+ therapies provide potential benefits over hCG monotherapy for pubertal induction in males with HH, regarding T levels and penile growth, with no difference in testicular growth between treatments. Prospective pediatric studies are needed to assess the benefits of these therapies in patients with HH and, ultimately, to establish guidelines for gonadotropin therapy in the adolescent population.

<![CDATA[Temperature preference of Nile tilapia (Oreochromis niloticus) juveniles induces spontaneous sex reversal]]>

Nile tilapia (Oreochromis niloticus) is an African freshwater fish that displays a genetic sex determination system (XX|XY) where high temperatures (above 32°C to 36.5°C) induce masculinization. In Nile tilapia, the thermosensitive period was reported from 10 to 30 days post fertilization. In their natural environment, juveniles may encounter high temperatures that are above the optimal temperature for growth (27–30°C). The relevance of the thermal sex reversal mechanism in a natural context remains unclear. The main objective of our study is to determine whether sexually undifferentiated juveniles spontaneously prefer higher, unfavorable temperatures and whether this choice skews the sex ratio toward males. Five full-sib progenies (from 100% XX crosses) were subjected to (1) a horizontal three-compartment thermal step gradient (thermal continuum 28°C– 32°C– 36.5°C) during the thermosensitive period, (2) a control continuum (28°C– 28°C– 28°C) and (3) a thermal control tank (36.5°C). During the first days of the treatment, up to an average of 20% of the population preferred the masculinizing compartment of the thermal continuum (36.5°C) compared to the control continuum. During the second part of the treatment, juveniles preferred the lower, nonmasculinizing 32°C temperature. This short exposure to higher temperatures was sufficient to significantly skew the sex ratio toward males, compared to congeners raised at 28°C (from 5.0 ± 6.7% to 15.6 ± 16.5% of males). The proportion of males was significantly different in the thermal continuum, thermal control tank and control continuum, and it was positively correlated among populations. Our study shows for the first time that Nile tilapia juveniles can choose a masculinizing temperature during a short period of time. This preference is sufficient to induce sex reversal to males within a population. For the first time, behavior is reported as a potential player in the sex determination mechanism of this species.

<![CDATA[Sexual dimorphism of acute doxorubicin-induced nephrotoxicity in C57Bl/6 mice]]>

Doxorubicin (DOX) is a chemotherapeutic agent that has been reported to cause nephrotoxicity in rodent models and to a lesser degree in cancer patients. Female rodents have been shown to be protected against several features of DOX-induced nephrotoxicity. Nevertheless, the underlying mechanisms of this sexual dimorphism are not fully elucidated. Therefore, in the current study, we investigated the sex and time-dependent changes in pathological lesions as well as apoptotic and fibrotic markers in response to acute DOX-induced nephrotoxicity. We also determined the effect of acute DOX treatment on the renal expression of the sexually dimorphic enzyme, soluble epoxide hydrolase (sEH), since inhibition of sEH has been shown to protect against DOX-induced nephrotoxicity. Acute DOX-induced nephrotoxicity was induced by a single intra-peritoneal injection of 20 mg/kg DOX to male and female adult C57Bl/6 mice. The kidneys were isolated 1, 3 and 6 days after DOX administration. Histopathology assessment, gene expression of the apoptotic marker, BAX, protein expression of the fibrotic marker, transforming growth factor-β (TGF-β), and gene and protein expression of sEH were assessed. DOX administration caused more severe pathological lesions as well as higher induction of the apoptotic and fibrotic markers in kidneys of male than in female mice. Intriguingly, DOX inhibited sEH protein expression in kidneys of male mice sacrificed at 3 and 6 days following administration, suggesting that induction of sEH is not necessary for acute DOX-induced nephrotoxicity. However, DOX-induced inhibition of renal sEH in male mice may protect the kidney from further DOX-induced injury in a negative feedback mechanism. We also observed lower constitutive expressions of TGF-β and sEH in the kidney of female mice which may contribute, at least in part, to sexual dimorphism of DOX-induced nephrotoxicity.

<![CDATA[Towards a new osteometric method for sexing ancient cremated human remains. Analysis of Late Bronze Age and Iron Age samples from Italy with gendered grave goods]]>

Sex estimation of human remains is one of the most important research steps for physical anthropologists and archaeologists dealing with funerary contexts and trying to reconstruct the demographic structure of ancient societies. However, it is well known that in the case of cremations sex assessment might be complicated by the destructive/transformative effect of the fire on bones. Osteometric standards built on unburned human remains and contemporary cremated series are often inadequate for the analysis of ancient cremations, and frequently result in a significant number of misclassifications. This work is an attempt to overcome the scarcity of methods that could be applied to pre-proto-historic Italy and serve as methodological comparison for other European contexts. A set of 24 anatomical traits were measured on 124 Bronze Age and Iron Age cremated individuals with clearly engendered grave goods. Assuming gender largely correlated to sex, male and female distributions of each individual trait measured were compared to evaluate sexual dimorphism through inferential statistics and Chaktaborty and Majumder’s index. The discriminatory power of each variable was evaluated by cross-validation tests. Eight variables yielded an accuracy equal to or greater than 80%. Four of these variables also show a similar degree of precision for both sexes. The most diagnostic measurements are from radius, patella, mandible, talus, femur, first metatarsal, lunate and humerus. Overall, the degree of sexual dimorphism and the reliability of estimates obtained from our series are similar to those of a modern cremated sample recorded by Gonçalves and collaborators. Nevertheless, mean values of the male and female distributions in our case study are lower, and the application of the cut-off point calculated from the modern sample to our ancient individuals produces a considerable number of misclassifications. This result confirms the need to build population-specific methods for sexing the cremated remains of ancient individuals.

<![CDATA[SUN-081 High Throughput Genetic Analysis Revealed Novel Genomic Loci and Candidate Genes Involved in Central Precocious Puberty Associated with Complex Phenotypes]]> <![CDATA[SUN-087 FGFR-Selective Tyrosine Kinase Inhibitors, Such as Infigratinib, Show Potency and Selectivity for FGFR3 at Pharmacologically Relevant Doses for the Potential Treatment of Achondroplasia]]> <![CDATA[SUN-LB16 Clitoromegaly in Premature Infants: Is It Truly Pathologic?]]> 9 mm or clitoral width >6 mm. Patients not meeting these criteria or those with clitoral edema, prominent clitoral hood were classified under false clitoromegaly. In the ‘no formal consult’ group, the documented discharge examination was used to assess persistence of clitoromegaly. Uni- and multi-variable logistic regression were used to determine factors that increased the likelihood of a formal consult. Results: 29 patients met inclusion criteria; 15 in the ‘formal consult’ group and 14 in the ‘no formal consult’ group. No significant differences were found between the groups in terms of birth weight, gestational age, race, ethnicity and maternal factors. History of IUGR (intrauterine growth restriction) was more common in the ‘formal consult’ group (60%) vs. ‘no formal consult’ group (21%) (p=0.04). Only 3/15 patients in the ‘formal consult’ group had true clitoromegaly; all 3 had normal 17-hydroxyprogesterone levels, and only 1 patient had transient elevation in androgen levels (androstenedione, deoxycortisol and testosterone). Of the ‘no formal consult’ group, only 3/14 patients had clitoromegaly noted on discharge; outcome was unknown for 1. Multi-variable logistic regression showed that lower gestational age (p=0.04) and history of IUGR (p=0.03), even after adjusting for birth weight, increased the likelihood of a formal consult. Conclusion: In summary, the majority of perceived clitoromegaly in premature infants is not associated with hormonal dysfunction. Lower gestational age and a history of IUGR increase the likelihood of a formal consult for clitoromegaly in these patients. Approximately half of the patients were noted to have false clitoromegaly indicating inconsistencies in examination technique and need for provider education. ]]> <![CDATA[SUN-084 A Quantitative-PCR Based Rapid and Cost-Effective Diagnostic Method for Turner Syndrome and Its Variants]]> 95% sensitivity and specificity. SHOX gene primer was the best to diagnose TS of all karyotypes combined and also classical TS(XO) from normal females. qPCR could also identify non-classical TS with >92% sensitivity and specificity,the best primer being ARSE, for detecting both mosaics and isochromosomes. The cut-offs determined from our study corroborates with past similar studies.1,2 qPCR using an appropriate panel of primers on the short and long arms of X chromosomes can be a rapid and cheaper alternative to karyotyping to diagnose TS of different karyotypes. The choice of primers should be guided by the need for a more sensitive or specific test depending on the clinical scenario. If used as a neonatal screening test, SHOX should be the best primer. For diagnostic purposes, when the pre-test probability is low, a more specific primer like SHOX would be more appropriate. However, when the pre-test probability is high, a sensitive primer for ruling out TS like VAMP7 is better. In case there is a high pre test probability of the patient having a non-classic TS rather than classic TS, ARSE should be used. This is the first study to show good sensitivity of qPCR in detecting non-classic TS of different karyotypes in addition to classic TS. References: 1. Ibarra-Ramírez M, Martínez-de-Villarreal LE. Clinical and genetic aspects of Turner’s syndrome. Medicina universitaria. 2016 Jan 1;18(70):42-8. 2 .Rocha MN et al. Applicability of real-time PCR methodology in the neonatal detection of Turner syndrome. Hormone and metabolic research. 2010 Aug;42(09):677-81. ]]> <![CDATA[SUN-086 Pilot Study Using Aromatase Inhibitor in Puberty of Boys With Partial Androgen Insensitivity: Report of Three Cases]]> <![CDATA[SUN-099 Seasonal Variations of 25-Hydroxy Vitamin D3, Parathyroid Hormone, and Alkaline Phosphatase in School-Aged Children]]> <![CDATA[SUN-093 Prospective Clinical Assessment Study in Children with Achondroplasia: The PROPEL Trial]]> <![CDATA[SUN-090 Investigation of Imprinting Defects in MKRN3 and DLK1 in Children with Idiopathic Central Precocious Puberty Through Specific DNA Methylation Analysis]]> <![CDATA[SUN-096 Incidentally Found Severe Hypercalcemia in a Pediatric Patient, Diagnostic Challenge]]> <![CDATA[SUN-101 Support for a New Therapeutic Approach of Using a Low-Dose FGFR Tyrosine Kinase Inhibitor (Infigratinib) for Achondroplasia]]> <![CDATA[SUN-LB17 The Association of Growth Hormone Treatment in Children With Short Stature With Idiopathic Scoliosis]]>