Dataset Information

Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences.

ABSTRACT: Do sex and maternal smoking effects on human fetal anogenital distance (AGD) persist in a larger study and how do these data integrate with the wider literature on perinatal human AGD, especially with respect to sex differences?Second trimester sex differences in AGD are broadly consistent with neonatal and infant measures of AGD and maternal cigarette smoking is associated with a temporary increase in male AGD in the absence of changes in circulating testosterone.AGD is a biomarker of fetal androgen exposure, a reduced AGD in males being associated with cryptorchidism, hypospadias and reduced penile length. Normative fetal AGD data remain partial and windows of sensitivity of human fetal AGD to disruption are not known.The effects of fetal sex and maternal cigarette smoking on the second trimester (11-21 weeks of gestation) human fetal AGD were studied, along with measurement of testosterone and testicular transcripts associated with apoptosis and proliferation.AGD, measured from the centre of the anus to the posterior/caudal root of penis/clitoris (AGD(app)) was determined in 56 female and 70 male morphologically normal fetuses. These data were integrated with current literature on perinatal AGD in humans.At 11-13 weeks of gestation male fetal AGD(app) was 61% (P< 0.001) longer than in females, increasing to 70% at 17-21 weeks. This sexual dimorphism was independent of growth characteristics (fetal weight, length, gonad weight). We confirmed that at 14-16 weeks of gestation male fetal AGD(app) was increased 28% (P < 0.05) by in utero cigarette smoke exposure. Testosterone levels were not affected by smoking. To develop normative data, our findings have been integrated with available data from in vivo ultrasound scans and neonatal studies. Inter-study variations in male/female AGD differences lead to the conclusion that normalization and standardization approaches should be developed to enable confidence in comparing data from different perinatal AGD studies.Sex differences, and a smoking-dependent increase in male fetal AGD at 14-16 weeks, identified in a preliminary study, were confirmed with a larger number of fetuses. However, human fetal AGD should, be re-assessed once much larger numbers of fetuses have been studied and this should be integrated with more detailed analysis of maternal lifestyle. Direct study of human fetal genital tissues is required for further mechanistic insights.Fetal exposure to cigarette smoke chemicals is known to lead to reduced fertility in men and women. Integration of our data into the perinatal human AGD literature shows that more work needs to be done to enable reliable inter-study comparisons.The study was supported by grants from the Chief Scientist Office (Scottish Executive, CZG/1/109 & CZG/4/742), NHS Grampian Endowments (08/02), the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 212885 and the Medical Research Council, UK (MR/L010011/1). The authors declare they have no competing interests, be it financial, personal or professional.

SUBMITTER: Fowler PA

PROVIDER: S-EPMC4716811 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences.

Fowler Paul A PA Filis Panagiotis P Bhattacharya Siladitya S le Bizec Bruno B Antignac Jean-Philippe JP Morvan Marie-Line ML Drake Amanda J AJ Soffientini Ugo U O'Shaughnessy Peter J PJ

Human reproduction (Oxford, England) 20160104 2

<h4>Study question</h4>Do sex and maternal smoking effects on human fetal anogenital distance (AGD) persist in a larger study and how do these data integrate with the wider literature on perinatal human AGD, especially with respect to sex differences?<h4>Summary answer</h4>Second trimester sex differences in AGD are broadly consistent with neonatal and infant measures of AGD and maternal cigarette smoking is associated with a temporary increase in male AGD in the absence of changes in circulatin ...[more]

PMID: 26732622

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Project description:BackgroundAnogenital distance (AGD), the distance between the anus and genitals, is in rodents a well-established marker of early androgen action and has been suggested to be so in humans as well. Thus, a link between human AGD and semen quality and potentially fecundity may exist.ObjectiveThe aim of this study was to assess the association between AGD and male factor infertility and among proven fertile men also time to pregnancy (TTP).Material and methodsAll included men were recruited from and examined at Copenhagen University Hospital - Rigshospitalet, Denmark (N = 388). Men with impaired semen quality were included from infertile couples (N = 128), and men with naturally conceived pregnant partners were invited to participate when their partners had their routine second trimester examination (N = 260). All men underwent a physical examination, completed a questionnaire (including TTP for the fertile men), delivered a semen sample and had a blood sample drawn. The primary exposure was AGDAS measured from the centre of the anus to the posterior base of the scrotum. Associations between AGD and fertility status as well as between AGD and TTP among the fertile men were calculated using multiple logistic regression adjusted for covariates.ResultsAGD did not show a statistically significant association with fertility status. In adjusted logistic regression models, the odds of infertility per 1 cm increase in AGDAS were 1.02 (95% confidence interval [CI]: 0.88; 1.19). Among fertile men, a 1-cm increase in AGDAS was associated with an 8% non-statistically significantly reduced odds of having a longer (>3months) TTP (adjusted odds ratio (OR) = 0.92, 95% CI: 0.76-1.11).ConclusionOur study showed that the clinical application of AGD as a predictor of fertility and fecundity seems to be limited as no associations were observed between AGD and fertility status, nor was the decreased risk of experiencing a longer TTP with longer AGDAS statistically significant.

Project description:Study questionCould the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis?Summary answerA short MRI-AGD is a strong diagnostic marker of endometriosis.What is known alreadyA short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis.Study design size durationThis study is a re-analysis of previously published data from a case-control study.Participants/materials setting methodsWomen undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF).Main results and the role of chanceThe study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3?mm (±3.9) and 21.2?mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P?<?10-5). Average MRI-AGD-AC measurements were 40.4?mm (±7.3) and 51.1?mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P?<?10-5). There was no difference of MRI-AGD in women with and without endometrioma (P?=?0.21), or digestive involvement (P?=?0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (? = -7.79, 95% CI (-9.88; -5.71), P?<?0.001) and MRI-AGD-AC (? = -9.51?mm, 95% CI (-12.7; 6.24), P?<?0.001) in multivariable analysis. Age (? = +0.31?mm, 95% CI (0.09; 0.53), P?=?0.006) and BMI (? = +0.44?mm, 95% CI (0.17; 0.72), P?=?0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20?mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted.Limitations reasons for cautionThis was a retrospective analysis and no adolescents had been included.Wider implications of the findingsThis study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis.Study funding/competing interestsN/A.Trial registration numberThe protocol was approved by the 'Groupe Nantais d'Ethique dans le Domaine de la Santé' and registered under reference 02651077.

Project description:In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2-4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

Dataset Information

Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences.

Publications

Human anogenital distance: an update on fetal smoke-exposure and integration of the perinatal literature on sex differences.

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