ResearchPad - testosterone https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Deletion of inositol polyphosphate 4-phosphatase type-II B affects spermatogenesis in mice]]> https://www.researchpad.co/article/elastic_article_14722 Inositol polyphosphate-4-phosphatase type II (INPP4B) is a dual-specificity phosphatase that acts as a tumor suppressor in multiple cancers. INPP4B dephosphorylates phospholipids at the 4th position of the inositol ring and inhibits AKT and PKC signaling by hydrolyzing of PI(3,4)P2 and PI(4,5)P2, respectively. INPP4B protein phosphatase targets include phospho-tyrosines on Akt and phospho-serine and phospho-threonine on PTEN. INPP4B is highly expressed in testes, suggesting its role in testes development and physiology. The objective of this study was to determine whether Inpp4b deletion impacts testicular function in mice. In testis, Inpp4b expression was the highest in postmeiotic germ cells in both mice and men. The testes of Inpp4b knockout male mice were significantly smaller compared to the testes of wild-type (WT) males. Inpp4b-/- males produced fewer mature sperm cells compared to WT, and this difference increased with age and high fat diet (HFD). Reduction in early steroidogenic enzymes and luteinizing hormone (LH) receptor gene expression was detected, although androgen receptor (AR) protein level was similar in WT and Inpp4b-/- testes. Germ cell apoptosis was significantly increased in the knockout mice, while expression of meiotic marker γH2A.X was decreased. Our data demonstrate that INPP4B plays a role in maintenance of male germ cell differentiation and protects testis functions against deleterious effects of aging and high fat diet.

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<![CDATA[A grape seed extract maternal dietary supplementation improves egg quality and reduces ovarian steroidogenesis without affecting fertility parameters in reproductive hens]]> https://www.researchpad.co/article/elastic_article_14599 In broiler hens, the genetic selection increased susceptibility to metabolic disorders and reproductive dysfunctions. In human ovarian cells, grape seed extracts (GSE) improved steroid production. Here, we investigated the effects of a GSE dietary supplementation on egg production and quality, fertility parameters, Reactive Oxygen Species (ROS) and steroid content in yolk egg associated to plasma adipokines in broiler hens. For this, we designed two in vivo experiments, the first one included three groups of hens: A (control), B and C (supplemented with GSE at 0.5% and 1% of the total diet composition, respectively, since week 4), and the second one used two groups of hens: A (control) and D (supplemented with GSE at 1% of the total diet composition since hatching). We assessed the egg production from 23th to 40th weeks and quality at 33th week. After artificial inseminations, the fertility parameters were calculated. In egg yolk, Reactive Oxygen Species (ROS) level and steroid production were evaluated by Ros-Glo H202 and ELISA assay, respectively. Expression of steroidogenic enzymes and adipokines and their receptors was determined by RT-qPCR in ovarian cells and plasma adipokines (RARRES2, ADIPOQ and NAMPT) were evaluated by specific ELISA assays. The fertility parameters and egg production were unaffected by GSE supplementation whatever the experiment (exp.). However, the rate of double-yolk eggs decreased for all GSE supplemented groups (exp. 1 P <0.01, exp.2, P<0.02). In exp.1, C group eggs were bigger and larger (P<0.0001) and the shell elasticity was higher for both B and C (P<0.0003) as compared to control. In the egg yolk, GSE supplementation in both exp. reduced ROS content and steroidogenesis consistent with a decrease in P450 aromatase and StAR mRNA expression and basal in vitro progesterone secretion in granulosa cells (P<0.001). Interestingly, in both exp. RARRES2 plasma levels were positively correlated while ADIPOQ and NAMPT plasma levels were negatively correlated, with steroids and ROS in yolk (P<0.0001). Taken together, maternal dietary GSE supplementation did not affect egg production and fertility parameters whereas it reduced ROS content and steroidogenesis in yolk egg. Furthermore, it ameliorated egg quality by decreasing the number of double-yolk eggs and by improving the size of normal eggs and the elasticity of the shell. Taken together, our data suggest the possibility of using dietary maternal GSE to improve egg quality.

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<![CDATA[Corticosterone and testosterone treatment influence expression of gene pathways linked to meiotic segregation in preovulatory follicles of the domestic hen]]> https://www.researchpad.co/article/elastic_article_14547 Decades of work indicate that female birds can control their offspring sex ratios in response to environmental and social cues. In laying hens, hormones administered immediately prior to sex chromosome segregation can exert sex ratio skews, indicating that these hormones may act directly on the germinal disc to influence which sex chromosome is retained in the oocyte and which is discarded into an unfertilizable polar body. We aimed to uncover the gene pathways involved in this process by testing whether treatments with testosterone or corticosterone that were previously shown to influence sex ratios elicit changes in the expression of genes and/or gene pathways involved in the process of meiotic segregation. We injected laying hens with testosterone, corticosterone, or control oil 5h prior to ovulation and collected germinal discs from the F1 preovulatory follicle in each hen 1.5h after injection. We used RNA-sequencing (RNA-seq) followed by DESeq2 and gene set enrichment analyses to identify genes and gene pathways that were differentially expressed between germinal discs of control and hormone-treated hens. Corticosterone treatment triggered downregulation of 13 individual genes, as well as enrichment of gene sets related to meiotic spindle organization and chromosome segregation, and additional gene sets that function in ion transport. Testosterone treatment triggered upregulation of one gene, and enrichment of one gene set that functions in nuclear chromosome segregation. This work indicates that corticosterone can be a potent regulator of meiotic processes and provides potential gene targets on which corticosterone and/or testosterone may act to influence offspring sex ratios in birds.

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<![CDATA[Heterochrony of puberty in the European badger (Meles meles) can be explained by growth rate and group-size: Evidence for two endocrinological phenotypes]]> https://www.researchpad.co/article/5c897769d5eed0c4847d2c1b

Puberty is a key stage in mammalian ontogeny, involving endocrinological, physiological and behavioural changes, moderated by intrinsic and extrinsic factors. Thus, not all individuals within one population achieve sexual maturity simultaneously. Here, using the European badger (Meles meles) as a model, we describe male testosterone and female oestrone profiles (using Enzyme-immunoassays) from first capture (3 months, post-weaning) until 28 months (attaining sexual maturity and final body size), along with metrics of somatic growth, scent gland development and maturation of external reproductive organs as well as intra-specific competition. In both sexes, endocrinological puberty commenced at ca. 11 months. Thereafter, cub hormone levels followed adult seasonal hormone patterns but at lower levels, with the majority of cubs reaching sexual maturity during their second mating season (22–28 months). Interestingly, there was evidence for two endocrinological phenotypes among male cubs (less evident in females), with early developers reaching sexual maturity at 11 months (first mating season) and late developers reaching sexual maturity at 22–26 months (second mating season). Early developers also attained a greater proportion of their ultimate adult size by 11 months, exhibiting faster growth rates than late developers (despite having similar adult size). Male cubs born into larger social groups tended to follow the late developer phenotype. Our results support the hypothesis that a minimum body size is required to reach sexual maturity, which may be achieved at different ages, even within a single population, where early maturity can confer individual fitness advantages and enhance population growth rate.

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<![CDATA[Molecular and genetic characterization of partial masculinization in embryonic ovaries grafted into male nude mice]]> https://www.researchpad.co/article/5c8977afd5eed0c4847d330e

In most of mammalian embryos, gonadal sex differentiation occurs inside the maternal uterus before birth. In several fetal ovarian grafting experiments using male host mice, an experimental switch from the maternal intrauterine to male-host environment gradually induces partial masculinization of the grafted ovaries even under the wild-type genotype. However, either host-derived factors causing or molecular basis underlying this masculinization of the fetal ovaries are not clear. Here, we demonstrate that ectopic appearance of SOX9-positive Sertoli cell-like cells in grafted ovaries was mediated by the testosterone derived from the male host. Neither Sox8 nor Amh activity in the ovarian tissues is essential for such ectopic appearance of SOX9-positive cells. The transcriptome analyses of the grafted ovaries during this masculinization process showed early downregulation of pro-ovarian genes such as Irx3, Nr0b1/Dax1, Emx2, and Fez1/Lzts1 by days 7–10 post-transplantation, and subsequent upregulation of several pro-testis genes, such as Bhlhe40, Egr1/2, Nr4a2, and Zc3h12c by day 20, leading to a partial sex reversal with altered expression profiles in one-third of the total numbers of the sex-dimorphic pre-granulosa and Sertoli cell-specific genes at 12.5 dpc. Our data imply that the paternal testosterone exposure is partially responsible for the sex-reversal expression profiles of certain pro-ovarian and pro-testis genes in the fetal ovaries in a temporally dependent manner.

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<![CDATA[The effect of endurance training and testosterone supplementation on the expression of blood spinal cord barrier proteins in rats]]> https://www.researchpad.co/article/5c6b2694d5eed0c484289cf8

The present study aimed to estimate the effect of endurance training, two doses of testosterone, and the combination of these stimuli on the level of the endothelial proteins claudin, occludin, JAM-1, VE-cadherin, ZO-1, ZO-2, and P-glycoprotein in rat spinal cords. Adult male Wistar rats were trained using a motor-driven treadmill for 6 weeks (40–60 min, 5 times per week) and/or were treated for 6 weeks with two doses of testosterone (i.m.; 8 mg/kg or 80 mg/kg body weight). Spinal cords were collected 48 hours after the last training cycle and stored at -80°C. The levels of selected proteins in whole tissue lysates of the spinal cord were measured by western blot. Testosterone-treated trained rats had significantly lower claudin levels than vehicle-treated trained rats. High doses of testosterone resulted in a significant decrease in claudin-5 in untrained rats compared to the control group. Both doses of testosterone significantly reduced occludin levels compared to those in vehicle-treated untrained rats. The JAM-1 level in the spinal cords of both trained and untrained animals receiving testosterone was decreased in a dose-dependent manner. The JAM-1 level in the trained group treated with high doses of testosterone was significantly higher than that in the untrained rats treated with 80 mg/kg of testosterone. VE-cadherin levels were decreased in all groups receiving testosterone regardless of endurance training and were also diminished in the vehicle-treated group compared to the control group. Testosterone treatment did not exert a significant effect on ZO-1 protein levels. Testosterone and/or training had no significant effects on ZO-2 protein levels in the rat spinal cords. Endurance training increased P-glycoprotein levels in the rat spinal cords. The results suggest that an excessive supply of testosterone may adversely impact the expression of endothelial proteins in the central nervous system, which, in turn, may affect the blood-brain barrier function.

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<![CDATA[Revisiting the Trivers-Willard theory on birth sex ratio bias: Role of paternal condition in a Malagasy primate]]> https://www.researchpad.co/article/5c269744d5eed0c48470f113

Within current theories on potential adaptive manipulation of offspring sex ratio, giving birth to a male or to a female is assumed to depend on the capacity of the mother to invest in offspring to maximize her fitness. The active role of the father in sex ratio bias at birth has been neglected until recently. The human sex ratio at birth is biased towards sons, although in occidental populations, the ratio has decreased regularly for 30 years and could be the consequence of the adverse effects of environmental chemicals on male hormones. In a Malagasy primate, the lesser mouse lemur, the potential effect of paternal testosterone levels on sex ratio bias at birth was tested on 130 litters (278 babies) produced in 52 mixed-sex groups. For each group, social dominance among males was characterized based on aggressive interactions and sexual behaviours. Using a multi correspondence analysis, high testosterone levels in grouped males, particularly those of the dominant male, were significantly correlated with more infants produced in male-biased litters, independent of the female condition. According to these results, predictions for sex ratio bias towards one sex or the other in mouse lemurs were discussed considering the influence of both parents.

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<![CDATA[New insights of polyamine metabolism in testicular physiology: A role of ornithine decarboxylase antizyme inhibitor 2 (AZIN2) in the modulation of testosterone levels and sperm motility]]> https://www.researchpad.co/article/5c23f275d5eed0c484046c9b

The specific role of polyamines in the testis physiology is not fully understood. Antizymes (OAZs) and antizyme inhibitors (AZINs) are modulators of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis and polyamine uptake. Although the three known OAZs are expressed in the testis, only OAZ3 is testis specific and has been proven to have an essential role in male fertility. Regarding the two existing AZINs, AZIN2 is the most abundantly expressed member in this gonad. Whereas previous studies suggested that AZIN2 might participate in mouse spermatogenesis, immunohistological analysis of human testicular sections revealed that AZIN2 is also detected in the steroidogenic Leydig cells but not in the germinal epithelium. In the present study, we found a close ontogenic similarity in the mRNA levels of OAZs and AZINs between mice and rats, but an opposite expression pattern of ODC activity. Further analysis of AZIN2 and OAZ3 in the testis of mice with different alterations in spermatogenesis and fertility, induced either genetically or pharmacologically, corroborated that both AZIN2 and OAZ3 are mainly expressed in the haploid germinal cells. Finally, by using transgenic mice with a truncated Azin2 gene fused to the bacterial lacZ gene, we studied the expression of Azin2 in testes, epididymides and spermatozoa. AZIN2 was detected in spermatids and spermatozoa, as well as in Leydig cells, and in epithelial epidydimal cells. Azin2 knock-out male mice were fertile; however, they showed marked decreases in testicular putrescine and plasma and testicular testosterone levels, and a dramatic reduction in the sperm motility. These results suggest an important role for AZIN2 in testicular cells by modulating polyamine concentrations, testosterone synthesis and sperm function. Overall, our data corroborate the relevance of polyamine regulation in testis functions, where both AZIN2 and OAZ3 play fundamental roles.

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<![CDATA[The relationship between iron deficiency anemia and sexual function and satisfaction among reproductive-aged Iranian women]]> https://www.researchpad.co/article/5c12cefcd5eed0c484913c90

Iron deficiency anemia (IDA) is a common micronutrient deficiency worldwide, and an important health problem especially in women of reproductive age. This study aimed to determine the relationship between IDA and sexual satisfaction and function among reproductive-aged Iranian women. In this study, 129 women (52 with IDA and 77 non-IDA) with age 18–45 in Mahshahr, Iran were recruited. Data was gathered by a demographic questionnaire, Female Sexual Function Index (FSFI) and Larson Sexual Satisfaction Questionnaire. Data were analyzed using an independent t-test, Mann-Whitney test, Chi-square, and correlation coefficient test. The results of this study showed that the means of hemoglobin (Hb), hematocrit (HCT), serum iron and ferritin were significantly lower in the IDA group than those in the non-IDA group (p<0.01). All dimensions of sexual function and satisfaction were significantly lower in women with IDA compared to the healthy women (p<0.001). Also, all blood indices for IDA had a significant relationship with all sexual function components and sexual satisfaction (p = 0.01) except for pain with Hb and ferritin. Health care providers should provide screening, education, and counseling about anemia and sexual function in reproductive age women.

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<![CDATA[Testosterone and Androgen Receptor Sensitivity in Relation to Hyperactivity Symptoms in Boys with Autism Spectrum Disorders]]> https://www.researchpad.co/article/5989da06ab0ee8fa60b75d78

Introduction

Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD.

Methods

In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3–15) with ASD is investigated. Given well documented differences in parent and trained examiners ratings of symptom severity, we employed a standardized parent`s questionnaire (Nisonger Child Behavior Rating Form) as well as a direct examiner`s rating (Autism diagnostic observation schedule) for assessment of hyperactivity symptoms.

Results

Although it was found there was no significant association between actual plasmatic testosterone levels and hyperactivity symptoms, the number of CAG triplets was significantly negatively correlated with hyperactivity symptoms (R2 = 0.118, p = 0.007) in the sample, indicating increased androgen receptor sensitivity in association with hyperactivity symptoms. Direct trained examiner´s assessment appeared to be a relevant method for evaluating of behavioral problems in the investigation of biological underpinnings of these problems in our study.

Conclusions

A potential ASD subtype characterized by increased rates of hyperactivity symptoms might have distinct etiopathogenesis and require a specific behavioral and pharmacological approach. We propose an increase of androgen receptor sensitivity as a biomarker for a specific ASD subtype accompanied with hyperactivity symptoms. Findings are discussed in terms of their implications for practice and future research.

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<![CDATA[Risk Preferences and Prenatal Exposure to Sex Hormones for Ladinos]]> https://www.researchpad.co/article/5989d9fbab0ee8fa60b7215a

Risk preferences drive much of human decision making including investment, career and health choices and many more. Thus, understanding the determinants of risk preferences refines our understanding of choice in a broad array of environments. We assess the relationship between risk preferences, prenatal exposure to sex hormones and gender for a sample of Ladinos, which is an ethnic group comprising 62.86% of the population of Guatemala. Prenatal exposure to sex hormones has organizational effects on brain development, and has been shown to partially explain risk preferences for Caucasians. We measure prenatal exposure to sex hormones using the ratio of the length of the index finger to the length of the ring finger (2D:4D), which is negatively (positively) correlated with prenatal exposure to testosterone (estrogen). We find that Ladino males are less risk averse than Ladino females, and that Ladino males have lower 2D:4D ratios than Ladino females on both hands. We find that the 2D:4D ratio does not explain risk preferences for Ladinos. This is true for both genders, and both hands. Our results highlight the importance of exploring the behavioral significance of 2D:4D in non-Caucasian racial groups.

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<![CDATA[60-Day Chronic Exposure to Low Concentrations of HgCl2 Impairs Sperm Quality: Hormonal Imbalance and Oxidative Stress as Potential Routes for Reproductive Dysfunction in Rats]]> https://www.researchpad.co/article/5989db4cab0ee8fa60bdab79

Mercury is a toxic and bio-accumulative heavy metal of global concern. While good deals of research have been conducted on the toxic effects of mercury, little is known about the mechanisms involved in the pathogenesis of male reproductive dysfunction induced by mercury. Therefore, the purpose of this study was to assess the effects and underlying mechanisms of chronic mercury exposure at low levels on male reproductive system of rats. Three-month-old male Wistar rats were divided into two groups and treated for 60 days with saline (i.m., Control) and HgCl2 (i.m. 1st dose: 4.6 µg/kg, subsequent doses 0.07 µg/kg/day). We analyzed sperm parameters, hormonal levels and biomarkers of oxidative stress in testis, epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm production, count and motility and increased head and tail morphologic abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels, increased lipid peroxidation on testis and decreased antioxidant enzymes activities (superoxide dismutase and catalase) on reproductive organs. Our data demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs sperm quality and promotes hormonal imbalance. The raised oxidative stress seems to be a potential mechanism involved on male reproductive toxicity by mercury.

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<![CDATA[Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor]]> https://www.researchpad.co/article/5ab18494463d7e5ca175d923

The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis.

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<![CDATA[Umbilical cord androgens and estrogens in relation to verbal and nonverbal abilities at age 10 in the general population]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc4a6

Sex differences in verbal and nonverbal abilities are a contentious area of research. Prenatal steroids have been shown to have masculinizing effects on the brain that may affect the development of nonverbal and verbal abilities in later life. The current study examined a wide range of biologically active sex steroids (both androgens and estrogens) in umbilical cord blood at birth in a large pregnancy cohort in relation to performance on nonverbal (Raven’s Coloured Progressive Matrices) and verbal (Clinical Evaluation of Language Fundamentals-3 and the Peabody Picture Vocabulary Test-III) measures at age 10 years. Overall, Androgen and Estrogen composites in cord blood were not found to be predictive of performance on verbal and nonverbal measures at age 10. These data suggest that late gestation sex steroids do not exert a major effect on nonverbal and verbal abilities in middle childhood.

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<![CDATA[Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study]]> https://www.researchpad.co/article/5989db02ab0ee8fa60bc6f6d

Aims

Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers.

Methods

This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18–50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically.

Results

Former AAS abusers exhibited significantly lower median (25th –75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9–17.7) nmol/l vs. 18.8 (16.6–22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05).

Conclusions

Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.

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<![CDATA[Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/5989da18ab0ee8fa60b7bf58

Background

The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood.

Methods

A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Results

Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41–1.16, P<0.001), with significant heterogeneity across studies (I2 = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92).

Conclusions

A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.

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<![CDATA[Endogenous Testosterone and Exogenous Oxytocin Modulate Attentional Processing of Infant Faces]]> https://www.researchpad.co/article/5989daa4ab0ee8fa60ba6d57

Evidence indicates that hormones modulate the intensity of maternal care. Oxytocin is known for its positive influence on maternal behavior and its important role for childbirth. In contrast, testosterone promotes egocentric choices and reduces empathy. Further, testosterone decreases during parenthood which could be an adaptation to increased parental investment. The present study investigated the interaction between testosterone and oxytocin in attentional control and their influence on attention to baby schema in women. Higher endogenous testosterone was expected to decrease selective attention to child portraits in a face-in-the-crowd-paradigm, while oxytocin was expected to counteract this effect. As predicted, women with higher salivary testosterone were slower in orienting attention to infant targets in the context of adult distractors. Interestingly, reaction times to infant and adult stimuli decreased after oxytocin administration, but only in women with high endogenous testosterone. These results suggest that oxytocin may counteract the adverse effects of testosterone on a central aspect of social behavior and maternal caretaking.

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<![CDATA[Does AMH Reflect Follicle Number Similarly in Women with and without PCOS?]]> https://www.researchpad.co/article/5989dab1ab0ee8fa60bab580

Context

Increased Anti-Mullerian Hormone in polycystic ovary syndrome, may be due to overactive follicles rather than reflect antral follicle count.

Objective

Does Anti-Mullerian Hormone reflect antral follicle count similarly in women with or without polycystic ovary syndrome or polycystic ovarian morphology?

Design

Cross-sectional, case-control.

Setting

Women who delivered preterm in 1999–2006. For each index woman, a woman with a term delivery was identified.

Patients

Participation rate was 69%. Between 2006–2008, 262 women were included, and diagnosed to have polycystic ovary syndrome, polycystic ovarian morphology or to be normal controls.

Intervention(s)

Blood tests, a clinical examination and vaginal ultrasound.

Main Outcome Measure(s)

Anti-Mullerian Hormone / antral follicle count -ratio, SHBG, androstenedione and insulin, to test potential influence on the Anti-Mullerian Hormone / antral follicle count -ratio.

Results

Mean Anti-Mullerian Hormone / antral follicle count ratio in women with polycystic ovary syndrome or polycystic ovarian morphology was similar to that of the controls (polycystic ovary syndrome: 1,2 p = 0,10 polycystic ovarian morphology: 1,2, p = 0,27 Controls 1,3). Anti-Mullerian Hormone showed a positive linear correlation to antral follicle count in all groups. Multivariate analysis did not change the results.

Conclusions

We confirmed the positive correlation between AMH and follicle count. Anti-Mullerian Hormone seems to be a reliable predictor of antral follicle count, independent of polycystic ovary syndrome diagnosis or ovarian morphology.

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<![CDATA[New NR5A1 mutations and phenotypic variations of gonadal dysgenesis]]> https://www.researchpad.co/article/5989db59ab0ee8fa60bdf189

Mutations in NR5A1 have been reported as a frequent cause of 46,XY disorders of sex development (DSD) associated to a broad phenotypic spectrum ranging from infertility, ambiguous genitalia, anorchia to gonadal dygenesis and female genitalia. Here we present the clinical follow up of four 46,XY DSD patients with three novel heterozygous mutations in the NR5A1 gene leading to a p.T40P missense mutation and a p.18DKVSG22del nonframeshift deletion in the DNA-binding domain and a familiar p.Y211Tfs*83 frameshift mutation. Functional analysis of the missense and nonframeshift mutation revealed a deleterious character with loss of DNA-binding and transactivation capacity. Both, the mutations in the DNA-binding domain, as well as the familiar frameshift mutation are associated with highly variable endocrine values and phenotypic appearance. Phenotypes vary from males with spontaneous puberty, substantial testosterone production and possible fertility to females with and without Müllerian structures and primary amenorrhea. Exome sequencing of the sibling’s family revealed TBX2 as a possible modifier of gonadal development in patients with NR5A1 mutations.

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<![CDATA[A mutation in the CACNA1C gene leads to early repolarization syndrome with incomplete penetrance: A Chinese family study]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf720

Background

Early repolarization syndrome (ERS) may be a near-Mendelian or an oligogenic disease; however, no direct evidence has been provided to support this theory.

Methods and results

We described a large Chinese family with nocturnal sudden cardiac death induced by ERS in most of the young male adults. One missense mutation (p.Q1916R) was found in the major subunit of the L-type calcium channel gene CACNA1C by the direct sequencing of candidate genes. A concomitant gain-of-function variant in the sodium channel gene SCN5A (p.R1193Q) was found to rescue the phenotype of the female CACNA1C-Q1916R mutation carriers, which led to the incomplete penetrance. The functional studies, via the exogenous expression approach, revealed that the CACNA1C-Q1916R mutation led to a decreasing L-type calcium current and the protein expression defect. The decreased calcium current produced by the mutant channel was improved by isoproterenol but exacerbated by testosterone. The effects of CACNA1C-Q1916R mutation and testosterone on cellular electrophysiology were further confirmed by the human ventricular action potential simulation.

Conclusions

Our results demonstrated that the loss-of-function CACNA1C-Q1916R mutation contributed to ERS-related sudden cardiac death, and the phenotypic incomplete penetrance was modified by the SCN5A-R1193Q variant and sex. These findings suggest that phenotypes of ERS are modified by multiple genetic factors, which supports the theory that ERS may be an oligogenic disease.

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