Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype.

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Testicular ectopia: Why does it happen and what do we do?

BACKGROUND/AIM: Testicular ectopia is rare, but the large range of anatomical locations described in the literature has spawned an abundance of possible theories to explain etiology. However, as the anatomical characteristics of normal testicular descent have only been elucidated recently, many of the theories of testicular ectopia do not incorporate this new perspective. In this study we aimed to determine what was in the literature about ectopic testis since 1980, and then try to explain the different anatomical variants in the light of current knowledge about testicular descent. METHODS: A literature search was performed and all articles in English published since 1980 about testicular ectopia using several key words were identified. RESULTS: A total of 271 articles in English were found, of which 31 addressed the pathophysiology and are the primary focus of this study. Case reports and reviews described perineal ectopia (×4), transverse testicular ectopia (×11), and abdominal ectopia (×2), along with 3 reviews/case reports addressing diagnosis and management. A range of proposed causes were found, including obstructed 'third inguinal ring' at neck of scrotum, abnormal CGRP function, aberrant distal gubernacular attachment, mechanical hindrance from retained Müllerian ducts, defective gubernacular formation or disruption of the gubernacular attachment to the testis. CONCLUSION: After reviewing the proposed theories, we propose a unifying theory, based on current knowledge of testicular descent, where testicular ectopia can be explained by a) anomalous attachment of the gubernaculum to the anterior abdominal wall during transabdominal descent, or b) aberrant migration of the gubernaculum during the inguinoscrotal phase of testicular descent.

Why do undescended testes and posterior urethral valve occur together?

BACKGROUND/AIM: Undescended testis (UDT) occurs in ~2 % of newborn males, and occasionally these infants also have posterior urethral valve (PUV). The cause of this relationship is uncertain. We aimed to review the literature to identify publications documenting co-occurrence of UDT and PUV, and to summarise the theories of co-occurrence. METHODS: A search of the literature (Embase, Medline, Pubmed; 1947-2015) was undertaken to identify publications describing the link between UDT in PUV patients, as well as PUV in UDT patients. Ten publications in English were found with both UDT and PUV: 9 articles describing the frequency of UDT in patients with PUV, and 1 article examining the frequency of PUV in infants with UDT. RESULTS: UDT occurred in 12-17 % of PUV compared with 1-2 % in the control population, consistent with a 10-fold increase. PUV occurred in 1.2 % of UDT patients compared with 0.01 % in the control population, consistent with a 100-fold increase. DISCUSSION: PUV leads to a 10-fold increase in occurrence of UDT, while the presence of UDT causes a 100-fold increase in occurrence of PUV. Four main theories of causation have been proposed, each of which have some merit but little supporting evidence, leaving the cause of simultaneous occurrence of PUV and UDT uncertain.