Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis
AGING-US
Authors: Ren, Xiaohan; Zhang, Tongtong; Chen, Xinglin; Wei, Xiyi; Tian, Ye; Li, Guangyao; Zhang, Xu; Zhang, Wei; You, Zebing; Wang, Shangqian; Qin, Chao
Abstract
We performed this meta-analysis to elucidate the associations between early-life BPA exposure and reproductive-related outcome indicators. The standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were measured by fixed-effects or random-effects models. The results revealed that BPA exposure at extremely-high dose (>50mg/kg/day) was significantly associated with negative reproductive-related outcomes (Prostate weight: SMD: -4.21; 95% Cl: -5.97, -2.44; Testis weight: SMD: -1.92; 95% Cl: -2.61, 1.23; Epididymis weight: SMD: -2.16; 95% Cl: -3.47, -0.86; Daily sperm production; SMD: -1.90; 95% Cl: -3.27, 0.53; Epididymal sperm count; SMD: -3.42; 95% Cl: -3.87, -2.97). Meanwhile, regardless of the dose, early-life BPA exposure could result in an adverse effect on sperm parameters of F1 generation male rodents at any period. Also, we found the non-monotonic dose response curves of BPA in specific tissues or organs, which may challenge the traditional mindset of "safe dose". This study demonstrated that bisphenol A exposure was relevant to adverse reproductive-related outcomes at specially appointed dose and period of life. Yet the assumption that no adverse effects can occur below the "safe" dose is suspected.
Effects of adult male rat feminization treatments on brain morphology and metabolomic profile
HORMONES AND BEHAVIOR
Authors: Gomez, Angel; Cerdan, Sebastian; Perez-Laso, Carmen; Ortega, Esperanza; Pasaro, Eduardo; Fernandez, Rosa; Gomez-Gil, Esther; Mora, Mireia; Marcos, Alberto; Rodriguez del Cerro, Maria Cruz; Guillamon, Antonio
Abstract
Body feminization, as part of gender affirmation process of transgender women, decreases the volume of their cortical and subcortical brain structures. In this work, we implement a rat model of adult male feminization which reproduces the results in the human brain and allows for the longitudinal investigation of the underlying structural and metabolic determinants in the brain of adult male rats undergoing feminization treatments. Structural MRI and Diffusion Tensor Imaging (DTI) were used to non-invasively monitor in vivo cortical brain volume and white matter microstructure over 30 days in adult male rats receiving estradiol (E-2), estradiol plus cyproterone acetate (CA), an androgen receptor blocker and antigonadotropic agent (E-2 + CA), or vehicle (control). Ex vivo cerebral metabolic profiles were assessed by 1 H High Resolution Magic Angle Spinning NMR HRMAS) at the end of the treatments in samples from brain regions dissected after focused microwave fixation (5 kW). We found that; a) Groups receiving E-2 and E-2 + CA showed a generalized bilateral decrease in cortical volume; b) the E-2 + CA and, to a lesser extent, the E-2 groups maintained fractional anisotropy values over the experiment while these values decreased in the control group; c) E-2 treatment produced increases in the relative concentration of brain metabolites, including glutamate and glutamine and d) the glutamine relative concentration and fractional anisotropy were negatively correlated with total cortical volume. These results reveal, for the first time to our knowledge, that the volumetric decreases observed in trans women under crosssex hormone treatment can be reproduced in a rat model. Estrogens are more potent drivers of brain changes in male rats than anti-androgen treatment.