Prenatal Androgen Research Articles

Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.

White matter variations in congenital adrenal hyperplasia: possible implications for glucocorticoid treatment.

Congenital adrenal hyperplasia has been reported to manifest with white matter aberrations. However, many previous studies included only small samples, restricted their analyses to females, lacked a control group and/or did not correct for brain size. Here, we examined the largest sample to date, comprising 53 male and female participants with congenital adrenal hyperplasia, who were matched with 53 male and female controls in terms of sex, age, education, and verbal intelligence. The four groups were compared with respect to their total white matter as well as white matter hyperintensities while applying brain size corrections. For both measures, total white matter and white matter hyperintensities, there were no significant sex differences or group-by-sex interactions. However, individuals with congenital adrenal hyperplasia had significantly smaller total white matter volumes compared to controls. Our findings align with previous reports of white matter variations in congenital adrenal hyperplasia. The absence of a group-by-sex interaction suggests that white matter variations in congenital adrenal hyperplasia may not be attributable to prenatal androgens. Instead, they may be a result of the condition itself and/or its treatment with glucocorticoids. The latter aspect warrants follow-up, particularly given that glucocorticoids are employed not only in congenital adrenal hyperplasia but also in other medical conditions.

Prenatal Exposure to Androgens and Gender Socialisation Effects on Children’s Academic Interests

Previous studies have documented gender differences in fields of study as well as interest in school subjects. Boys are on average more interested in mathematics, and girls show greater interest in languages. The extent to which these disparities are the result of biological or environment influences is still an open debate. On the one hand, brain organisation theory suggests that physiological and behavioural differences may be linked to prenatal hormone levels. On the other hand, sociological and psychological perspectives highlight the importance of gender socialisation. This paper combines biological, psychological, and sociological perspectives to examine the emergence of gendered academic interests in children.The study draws on data from 9‑year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Our results suggest that for both boys and girls, medium to high compared with low prenatal exposure to circulating maternal testosterone might increase children’s interests in mathematics relative to English, although results vary depending on how prenatal testosterone exposure is measured. As the distributions of prenatal androgen exposure and the relationships with maths versus English interests are very similar for boys and girls, prenatal androgen exposure does not contribute to explaining gender differences in academic interests. However, we find some evidence that the relationship with parental gender socialisation varies by prenatal androgen exposure. A more gender-equal parental division of domestic work is more strongly associated with less gendered academic interests for girls with low prenatal androgen exposure and for boys with medium to high androgen exposure.

Second and fourth (2D:4D) digit ratio in heroin and cannabis addicted patients

The etiology of addiction has not yet been fully elucidated. The ratio between the length of the second and fourth fingers (2D:4D ratio) has been linked with prenatal androgen concentrations, but also with addictive behvaiors. Aim: The present study aimed to evaluate the differences of 2D:4D ratio of individuals with cannabis and heroin addiction by examining them together with the control group. A total of sixty two male patients (33 opiate use disorder and 29 cannabis use disorder) with substance use disorder and the twenty-nine healthy controls were included in the present investigation. We obtained the lengths of 2D and 4D of the subjects by using sensitive calipers and calculated the 2D:4D. Heroin-addicted patients had lower 2D:4D ratio in in the right hand (significant difference between control group) (p < 0.001), there was no significant difference found between heroin-cannabis (p = 0.242) and control-cannabis 2D:4D ratios (p < 0.06). In the left hand, it was significant between the heroin-control groups (p < 0.037) and the cannabis-control groups (p < 0.023), while it was not significant between the heroin-cannabis groups (p = 1). In conclusion, we suggest that heroin-and cannabis addicted patients seem to have a lower ratio of 2D:4D compared to healthy control subjects. Our findings can be considered promising as to whether prenatal hormonal factors are important in the etiopathogenesis of addiction.

Digit Ratio (2D:4D; Right-Left 2D:4D) and Multiple Phenotypes for Same-Sex Attraction: The BBC Internet Study Revisited

Same-sex attraction may be linked to low prenatal androgen (in men) and high prenatal androgen (in women). Digit ratio (2D:4D) is thought to be a negative correlate of prenatal androgen and right-left 2D:4D (Dr-l) to reflect lateralized differences in sensitivity to prenatal androgen. Lower 2D:4D has been reported for lesbians compared to heterosexuals, but links to high 2D:4D in gay men are less clear. The largest study thus far (the BBC Internet study) found no significant difference between the 2D:4D of lesbians and heterosexual women but a higher 2D:4D in gay men compared to heterosexual men. Here we consider the possibility that low and high prenatal androgen is associated with same-sex attraction in men (n = 108,779) and women (n = 87,742), resulting in more than two phenotypes. We examined the associations between 2D:4D, Dr-l, and same-sex attraction scores in the BBC Internet study. In contrast to the earlier report, which considered sexual orientation in categories, there were positive linear associations in men (right and left 2D:4D, but not Dr-l) and negative linear associations in women (right 2D:4D and Dr-l, but not left 2D:4D). There were no curvilinear relationships for right and left 2D:4D. However, Dr-l showed a U-shaped association with same-sex attraction in men. Thus, (1) high prenatal androgen may be implicated in female homosexuality, while both low and high prenatal androgen may be implicated in male homosexuality, and (2) large side differences in sensitivity to androgen may be associated with elevated same-sex attraction in men.

FRI278 Kisspeptin Neuron Projections And Expression Patterns Are Unaltered In Prenatally Androgenized Female Mice Modeling PCOS

Abstract Disclosure: M. Prescott: None. Y. Watanabe: None. A. Ruddenklau: None. L. Fisher: None. C.L. Jasoni: None. R.E. Campbell: Consulting Fee; Self; Bayer, Inc. Polycystic ovary syndrome (PCOS) is associated with impaired gonadal steroid hormone feedback and a hyperactive central reproductive axis, implicating the brain in PCOS pathophysiology. Excess prenatal androgen (PNA) exposure is linked with the development of PCOS, and preclinical evidence suggests that PNA can program altered connections within the gonadotropin-releasing hormone (GnRH) neuronal network. Kisspeptin neurons are critical upstream regulators of GnRH neurons, relaying hormone feedback and potently activating GnRH secretion, but their role in PCOS remains incompletely understood. This study tested the hypothesis that prenatal androgen excess programmes altered neuroanatomical connections between kisspeptin neurons and GnRH neurons and modified neuropeptide and steroid hormone receptor expression in kisspeptin neurons. To investigate this, we labelled, imaged and assessed kisspeptin fibers, GnRH neurons, and gonadal steroid hormone receptors in adult female transgenic kisspeptin reporter mice (Kiss1(Cre-GFP)Coll; ROSA26tdTomato) exposed prenatally to di-hydrotestosterone or an oil vehicle (VEH) on gestational days 16-18 (n=7-10/group). PNA mice were acyclic and all tissue was collected in diestrus. Fixed coronal brain sections were immunofluorescently labelled for GnRH and kisspeptin reporter tdTomato and imaged on a confocal microscope to assess close fiber contacts to the soma and proximal dendrite of GnRH neurons. Neither the proportion of GnRH neurons with kisspeptin fiber contacts (VEH: 86.3±3.4%, PNA: 87.3±4.3%), nor the mean number of kisspeptin fiber close appositions per GnRH neuron (VEH: 6.1±0.6, PNA: 5.7±0.8) was different between groups. Kisspeptin neuron number and kisspeptin neuron co-expression with estrogen and progesterone receptors was evaluated in immunolabelled sections throughout the rostral periventricular nucleus of the 3rd ventricle (RP3V) and the arcuate nucleus (ARN). PNA had no significant impact on kisspeptin neuron number or the proportion of neurons with gonadal hormone co-expression in either population. Expression of neuropeptides was quantified by RT-qPCR in micro-dissected RP3V and ARN tissue from a separate cohort of adult PNA and VEH mice (n=5-8/group). PNA did not affect Kiss1, Tac2 or Pdyn expression in the ARN or Kiss1 expression in the RP3V. These data indicate that PNA does not modify anatomical connections between RP3V kisspeptin neurons and GnRH neurons, nor does it have a robust impact on steroid hormone responsiveness or neuropeptide expression of kisspeptin neurons. While the neuroanatomical relationship between ARN kisspeptin neurons and the GnRH neuron distal dendron in PNA mice remains to be determined, these data suggest that PNA-mediated neuroendocrine dysfunction is not due to programmed changes in the neuroanatomical projections or gonadal hormone sensitivity of kisspeptin neurons. Presentation: Friday, June 16, 2023

FRI284 The GnRH Pulse Generator Activity In Mouse Models Of Polycystic Ovary Syndrome

Abstract Disclosure: Z. Zhou: None. M. Pardo-Navarro: None. S.Y. Han: None. A.E. Herbison: None. Up to one in five women worldwide suffer from polycystic ovary syndrome (PCOS), a condition typified by problems with fertility, high androgen levels, and altered metabolism. Primarily due to the unknown aetiology of this disorder, limited strategies are available for PCOS treatment. The hypothalamic GnRH pulse generator is responsible for driving the pulsatile release of LH to control ovarian function. As PCOS patients show profound increase in LH pulse frequency, it is thought that over-activity of the GnRH pulse generator may have a major role in generating the sub-fertility of women with PCOS. Recent studies involving the real-time imaging of neural activity in genetic mouse models have revealed that a population of kisspeptin neurons located in the arcuate nucleus of the hypothalamus is the long-sought after “GnRH pulse generator”. These arcuate kisspeptin neurons exhibit synchronization events (SEs) that correlate perfectly with pulsatile LH secretion. With this technique, we aimed to characterize the activity pattern of the arcuate kisspeptin neurons in two most-widely used mouse models of PCOS: prenatal androgen (PNA) and peripubertal androgen models. In the first model, PNA female mice exhibited near-acyclic estrous cycles as previously reported, but surprisingly exhibited only a slightly (∼30%) increased frequency of arcuate kisspeptin neuron SEs over a 24-hour recording period compared to the controls. The profiles and dynamics of individual SEs were not different between PNA and control animals. Concurrent fiber photometry recording and serial blood sampling showed that each SE is tightly followed by an LH pulse in all animals. Three weeks following ovariectomy, the SE frequency and profile were not different between PNA and control mice. In the second peripubertal model, female mice implanted with dihydrotestosterone capsules at 3-weeks of age exhibited significant weight gain but decreased arcuate kisspeptin neuron activity over a 24-hour recording period also without changes in SE dynamics compared to the controls. In conclusion, it appears that neither of the two most-commonly used PCOS mouse models mirror the human condition in which many PCOS women exhibit robust increases in pulsatile LH secretion. Presentation: Friday, June 16, 2023

THU650 Prevalence Of Hyperandrogenemia, PCOS And Obesity In Mothers Of Daughters With PCOS

Abstract Disclosure: J. Cai: None. K. Brewer: None. R. Sisk: None. R.S. Legro: None. A.E. Dunaif: None. Prenatal exposure to androgens produces phenocopies of PCOS in animal models. In mice, there is evidence for transgenerational prenatal androgen effects. Human studies considered to support the hypothesis that intrauterine actions of androgens play a major role in PCOS pathogenesis come from (1) health registries where PCOS in mothers and daughters was diagnosed by ICD codes and (2) retrospective assessment of mother’s PCOS status in cohorts of affected women. Maternal PCOS status has not been directly assessed. As part of our genetic analyses of PCOS, we have prospectively recruited 678 mothers and 540 fathers of 678 women fulfilling NIH criteria for PCOS with confirmed hyperandrogenism and ovulatory dysfunction (OD). All subjects had fasting blood samples for reproductive hormones measured in central labs. Mothers completed a validated questionnaire for reproductive history. We tested the hypothesis that maternal PCOS accounted for PCOS in her daughter. We also investigated the contribution of maternal compared to paternal obesity to daughters’ obesity. We limited the analysis to mothers age 50 yrs and younger, with FSH &amp;lt;40 mIU/mL; 108 fathers were available from these families. Continuous data are reported as median and data range. Age (yrs): daughters 23 (13-24), mothers 46 (34-50), fathers 48 (37-69). Daughters had significantly higher BMI (kg/m2) (35.3, 18.5-60.0) than mothers (28.9, 18.7-54.1) and fathers (29.6, 18.4-55.5) (both P &amp;lt;0 .0001), while BMI did not differ in mothers and fathers. Hyperandrogenemia (HA), defined as total testosterone &amp;gt;58 ng/dL, biologically available testosterone &amp;gt;15 ng/dL or DHEAS &amp;gt;2683ng/mL, was present in 14.4% (20/139) of mothers, of these, 2.2% (3/139) fulfilled NIH criteria for PCOS, HA+OD. The prevalence of obesity, BMI ≥ 30.0 kg/m2, (66.2% daughter, 44.8% mother, and 45.7% fathers) was increased in daughters compared to both mothers (p= 0.0004) and fathers (p&amp;lt; 0.0001). Mothers with HA had higher BMI than those without it (P= 0.011). The odds ratio for obesity in daughters was 5.16 (1.97, 13.48) with maternal obesity and 2.29 (0.95, 5.52) with paternal obesity. Only ∼14% of reproductive-age mothers had HA, which we have shown in an underlying reproductive phenotype in PCOS families (Legro. Proc Natl Acad Sci USA, 1998); ∼ 2% of mothers fulfilled NIH criteria for PCOS. Although the PCOS reproductive phenotype ameliorates with age, it is clear that many affected daughters did not have a mother with hormonal features of PCOS. These findings do not support the hypothesis that prenatal androgen exposure is a final common path to PCOS in humans. The prevalence of obesity was higher in daughters than in parents and in HA mothers compared mothers without HA suggesting that obesity was associated with features of PCOS. Maternal obesity conferred greater risk for obesity in daughters than paternal obesity. Presentation: Thursday, June 15, 2023

The associations between 2D:4D ratio and behavior problems among Chinese preschool children: A cross-sectional study

BackgroundDigit ratio (2D:4D) is considered a biomarker of prenatal androgen activity, the prenatal hormone exposure may affect children's psychology and behavior. ObjectiveThe aim of this study was to analyze the associations between 2D:4D ratio and behavior problems in Chinese preschool children, and to provide ideas for early intervention of children's behavior problems. MethodsA total of 548 Chinese preschool children aged 3–6 years were recruited using a stratified cluster sampling method. The Child Behavior Checklist (CBCL) was used to assess the children's behavior. Basic information of the children and their parents was also collected, finger length was directly measured by electronic vernier caliper. ResultsWe found that sex and age of the child, mother's educational level, and whether the child was an only child were the influencing factors of behavior problems (P < 0.05). Right-handed 2D:4D was negatively correlated with parent-reported anxiety/depression (P < 0.05), father-reported aggression (P < 0.05) and attention problems (P < 0.01), that is, high levels of testosterone may increase the risk of anxiety and depression, our results were in contrast to previous studies. ConclusionThe 2D:4D ratio may be related to behavior problems among Chinese preschool children, and prenatal testosterone exposure may be an important factor affecting behavior problems.

Effects of an App-Based Mindfulness Intervention during Pregnancy on the Infant's Prenatal Androgen Exposure: A Randomized Controlled Pilot Trial.

Prenatal androgen exposure modulates the development of the brain, with lasting effects on its function and behavior over the infant's life span. Environmental factors during pregnancy, in particular maternal stress, have been shown to influence the androgen load of the unborn child. We here addressed the research gap on whether a mindfulness intervention or a pregnancy education administered to pregnant women more affects the androgen exposure of the unborn child (quantified by the proxies of second-to-fourth digit length ratio (2D:4D) and anogenital distance assessed one year after delivery and at delivery, respectively). Moreover, we tested the mindfulness intervention's effects on maternal perceived stress, anxiety, depressiveness, and mindfulness. Pregnant women (gestation weeks 8-14) were randomized to a 15-week app-based mindfulness-oriented intervention (N = 72) or a pregnancy education intervention (control condition; N = 74). The mindfulness-oriented group did not significantly differ from the pregnancy education group in infants' 2D:4D or anogenital distance (partial η2 ≤ 0.01) or in maternal stress, anxiety, depressiveness, or mindfulness. However, the descriptive results indicate that across pregnancy, stress and anxiety decreased and mindfulness increased in both groups. Overall, this study did not show that the mindfulness intervention (relative to the pregnancy education) reduced the prenatal androgen exposure of the unborn children or improved the maternal outcomes significantly.

Supplemental Material for Gender Identity, Sexual Orientation, and the Prenatal Androgen Theory: Reevaluating Definitions, Cognitive Tests, and Somatic Markers

Supplemental Material for Gender Identity, Sexual Orientation, and the Prenatal Androgen Theory: Reevaluating Definitions, Cognitive Tests, and Somatic Markers

Gender identity, sexual orientation, and the prenatal androgen theory: Reevaluating definitions, cognitive tests, and somatic markers.

Gender identity, sexual orientation, and the prenatal androgen theory: Reevaluating definitions, cognitive tests, and somatic markers.

Analysis of Methylome, Transcriptome, and Lipid Metabolites to Understand the Molecular Abnormalities in Polycystic Ovary Syndrome.

This study aimed to identify differentially methylated genes (DMGs) and differentially expressed genes (DEGs) to investigate new biomarkers for the diagnosis and treatment of polycystic ovary syndrome (PCOS). To explore the potential biomarkers of PCOS diagnosis and treatment, we performed methyl-binding domain sequencing (MBD-seq) and RNA sequencing (RNA-seq) on ovarian granulosa cells (GCs) from PCOS patients and healthy controls. MBD-seq was also performed on the ovarian tissue of constructed prenatally androgenized (PNA) mice. Differential methylation and expression analysis were implemented to identify DMGs and DEGs, respectively. The identified gene was further verified by real-time quantitative PCR (RT-qPCR) and methylation-specific PCR (MSP) in clinical samples. Furthermore, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was carried out on PCOS patients and healthy controls to identify differential lipid metabolites. Compared to the control group, 13,526 DMGs related to the promoter region and 2429 DEGs were found. The function analysis of DMGs and DEGs showed that they were mainly enriched in glycerophospholipid, ovarian steroidogenesis, and other lipid metabolic pathways. Moreover, 5753 genes in DMGs related to the promoter region were screened in the constructed PNA mice. Integrating the DMGs data from PCOS patients and PNA mice, we identified the following 8 genes: CDC42EP4, ERMN, EZR, PIK3R1, ARHGEF18, NECTIN2, TSC2, and TACSTD2. RT-qPCR and MSP verification results showed that the methylation and expression of TACSTD2 were consistent with sequencing data. Additionally, 15 differential lipid metabolites were shown in the serum of PCOS patients. The differential lipids were involved in glycerophospholipid and glycerolipid metabolism. Using integration of methylome and lipid metabolites profiling we identified 8 potential epigenetic markers and 15 potential lipid metabolite markers for PCOS. Our results suggest that aberrant DNA methylation and lipid metabolite disorders may provide novel insights into the diagnosis and etiology of PCOS.

Prenatal androgenization triggered neuroimmune alterations in the fetal ovary and programmed its persisting dysfunction

Prenatal androgenization triggered neuroimmune alterations in the fetal ovary and programmed its persisting dysfunction

Prenatal androgenization (2D:4D) predictions of tennis match-play success in junior players: A search for physiological explanations.

This study aims to investigate the possible association between digit ratio (2D:4D) and match-play success (MPS) in junior tennis players. In addition, we consider the possible explanatory pathways of these associations in relation to psychological, strength, power, and hormonal parameters. We performed a cross-sectional study, with a sample comprised of 64 male junior tennis players (11-18 years old). Digit ratio was calculated from direct finger measurements. In addition, we measured the ratio of wins by number of matches played in 5 years of official competition (MPS), handgrip strength (HGS), standing long jump (SLJ), training (in weekly hours), and expertise (number of years in official competition). Salivary testosterone and cortisol levels were measured before and after physical "challenge" tests. The 2D:4D correlated negatively with HGS and SLJ. MPS was also negatively associated with 2D:4D, but was positively correlated to HGS, expertise, training, and self-confidence (SC). Multiple linear regression showed 2D:4D and expertise were associated with MPS (43%-54%). None of the physical, or hormonal variables tested explained the links between 2D:4D and MPS. Therefore, the specific fitness components influenced by prenatal androgenization that moderate sports success remain unknown. Future studies should explore the interaction of 2D:4D, with tennis exercises as a challenge to induce hormonal change, the effect of pubertal stage, and the influence of aerobic endurance in determining MPS.

Finger-Length Ratios and Sexual Orientation in Southern Spain: A Large Sample Study on Sex-Linked Personality and Cognitive Traits.

Some similarities between sex differences and sexual orientation differences, with gay men shifted in female-typical directions and lesbians shifted in male-typical directions, have been hypothesized to reflect the effects of prenatal androgen exposure. This report assessed sex-linked personality and cognitive traits in a Spanish sample of 1117 straight (i.e., heterosexual) and non-straight (i.e., non-heterosexual) men and women, using finger-length ratio (2D:4D) as an index of prenatal androgen exposure. Observed sex differences were in the expected direction: Measures of right-hand 2D:4D, left-hand 2D:4D, and anxiety were higher in straight women than men, whereas impulsivity, dominance, cognitive reflection, and mathematical proficiency were higher in straight men than women. Gay men proved to be shifted in a female-typical direction compared to straight men for right-hand 2D:4D, left-hand 2D:4D, anxiety, and cognitive reflection; they were intermediate for dominance and mathematics, and were shifted in a male-typical direction for impulsivity. Lesbians were shifted in a male-typical direction compared to straight women for left-hand 2D:4D, anxiety, cognitive reflection, and mathematics; and they were shifted in a highly female-typical direction for impulsivity and dominance (scoring lower than straight women). Observed sex-linked shifts in gay men and lesbians were larger for psychological traits that displayed larger sex differences, and smallest for impulsivity (which displayed the smallest sex difference). Evidence also suggested that sex-related measures were linked to 2D:4D in theoretically meaningful ways. In conclusion, this report suggests a plausible role of androgens as prenatal determinants of sex-linked personality and cognitive traits in straight and non-straight men and women.

Anogenital Distance and Prenatal Androgen Exposure in Female Fetus and Newborns: A Systematic Review

The aim of this systematic review is to examine the relationship between anogenital distance (AGD) and prenatal androgen exposure in female offspring, and to assess whether there is sufficient scientific evidence that AGD could be a biomarker of in utero exposure in girls. A systematic approach was adopted to the screening and selection of the studies through Pub Med database. 959 documents were found in Pub Med search, 919 of them were excluded for lack of relevance, and 40 studies were included in the review. A significant portion of the selected studies (25 papers) focuses on the effect of exposure to endocrine disrupting agents (EDAs) such as phthalates, bisphenol A, and perfluoroalkyl substances. The other exposure factors examined in the studies are polycystic ovary syndrome, smoking and alcohol use, and maternal stressful life events. In 19 studies, a significant association has been reported between prenatal exposure factors and AGD length in female fetus and newborns. In the remaining 21 studies, no significant association was found. In conclusion, although there is still no a clear and conclusive evidence, a growing body of research provides data supporting that AGD may be considered a reliable marker of in utero androgen exposure in female infants. Our review highlights significant knowledge gaps with regard to some androgen or anti-androgen exposure factors. Much more research needed to understand the relationship of anogenital distance with in utero hormonal milieu and offspring’s reproductive system development.

The anogenital ratio as an indicator of reproductive performance in dairy heifers

The anogenital distance (AGD) is considered a marker for prenatal androgen exposure and fertility in multiple species including humans. In dairy cattle, it is described as the length between the center of the anus and the clitoral base (AGDc). However, in other species, the distance from the center of the anus to the dorsal commissure of the vulva (AGDv) is also considered to be a predictor for fertility traits, as well as the anogenital ratio (AGR, defined as [AGDv/AGDc]*100). The primary aim of the present study was to assess whether AGDv and AGR can be used as an indicator for reproductive performance in dairy heifers. Additionally, the relation between AGDv and AGDc and the correlation with other body measurements were explored. Data of 656 Holstein Friesian heifers at an age of 13.5 ± 1.08 months were analyzed. Respective means of 62.9 ± 8.20 mm (AGDv) and 107.6 ± 9.27 mm (AGDc) were recorded. The mean AGR ratio was calculated as 58.6 ± 6.75%, varying from 37.3 to 79.6%. The age of the heifers was not associated with any of the AGD measurements nor the ratio. Except for a very low correlation between heart girth and AGDc (r = 0.09, P < 0.05), both AGDs were largely uncorrelated with other body measurements. Linear regression models revealed that AGDc was not associated with any of the recorded fertility parameters. However, results revealed a negative association between AGDv and AGR and reproductive performance: heifers with a short AGDv and small AGR were younger at first AI (P ≤ 0.003) and at conception (P = 0.004). Based on ROC curve analyses, AGDv was the best indicator for pregnancy to first AI, with a threshold estimated at 65.3 mm. The pregnancy rate at first AI was 72.4% in heifers with a short AGDv (<65.3 mm, n = 413) compared to 61.7% in heifers with a long AGDv (≥65.3 mm, n = 243). Hence, short-AGDv heifers had 63% higher odds to conceive at first AI compared to their long-AGDv counterparts (P = 0.004). Additionally, an AGR threshold of 59,6% was determined: heifers with a small AGR (<59.6%) had 44% higher odds to be pregnant at first AI compared to heifers with an AGR ≥59.6%. Results of the present study suggest to consider AGDv and AGR as potential indicators for reproductive performance in dairy heifers. The latter implies that it is relevant to measure both AGDc and AGDv in future studies. The absence of correlation between body- and AGD-measurements furthermore suggests that AGD sizes are rather pre-than postnatally determined.

Self-Efficacy and the Digit Ratio in a Group of Sports University Students.

Self-efficacy is one's awareness of being able to cope optimally with different situations. Perceived self-efficacy is a belief that closely involves emotional and personological functioning. In fact, when one perceives oneself as capable, the likelihood of success increases significantly. The aim of this research was to verify a possible correlation between self-efficacy and the Digit Ratio (2D:4D), referred to as prenatal androgen levels, and whether these correlate with some psychological variables, considering possible gender differences. This study involved 56 sports university students, whose 2D:4D ratio was calculated. Moreover, self-assessment questionnaires: the Self-efficacy Scale (SES), the Big Five Questionnaire-2 (BFQ-2), the Profile of Mood State (POMS), the State-Trait Anxiety Inventory Form Y (STAI-Y) and the Emotional Regulation Questionnaire (ERQ) were administered. The data show that the perceived levels of self-efficacy seem to be influenced by an innate predisposition linked to prenatal androgen values to which the subjects were exposed during uterine life (2D:4D). This negative correlation indicates that the higher the value of the digit ratio, the more likely it is that the level of perceived self-efficacy will be lower. Finally, the degree of perceived self-efficacy also seems to depend on the levels of subjective anxiety, understood both as a personological disposition and a contingent condition, and the latter also seems to be influenced by prenatal androgen levels, particularly in women.

Longer anogenital distance in female fetus of diabetic and obese pregnant women

ObjectivePrevious studies revealed that prenatal exposure to androgen excess such as polycystic ovary syndrome (PCOS) is associated with offspring's anogenital distance (AGD) length, and AGD is a biomarker of intrauterine androgen exposure. This study aims to investigate a possible relationship of fetal AGD with maternal diabetes and obesity, and to evaluate whether AGD predicts the fetal androgen exposure related to diabetes and obesity in female fetus. This study is the first to focus on the relationship between offspring's AGD and maternal diabetes and obesity. Materials and methodsThis is a prospective study investigating 218 pregnant women (125 in control group and 93 in study group). Fetal AGD was measured from the center of anus to the posterior convergence of the fourchette by ultrasound. Multivariate linear regression analysis was applied to assess the association of the fetal AGD length with maternal diabetes and obesity. ResultsThe control patients had significantly shorter fetal AGD (mean:10.7 mm, P < 0.001) compared to diabetic, obese and diabetic obese patients (mean: 12.6 mm, 12.8 mm and 12.9 mm, respectively). The results of regression analysis showed that both maternal diabetes and obesity were significantly correlated with longer AGD in female fetus. The results confirmed also that offspring's AGD measurement in utero by ultrasound is feasible and reliable. ConclusionThe study findings suggest that both maternal diabetes and obesity are associated with intrauterine androgenic milieu during pregnancy, and fetal AGD may be used as a biomarker to predict this effect. This may provide important advantages in terms of early detection of reproductive system abnormalities related to prenatal androgen exposure.