Distinct Transcriptional Profiles of the Female, Male, and Finasteride-Induced Feminized Male Anogenital Region in Rat Fetuses

Abstract

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In vitro and in vivo endocrine disrupting effects of the azole fungicides triticonazole and flusilazole

“…It could be speculated that flusilazole induces opposing endocrine disruptive mechanisms of action, where an inhibitory effect on the androgen receptor is counteracted by an inhibitory effect on aromatase causing high fetal androgen levels. Notably, recent data suggests that estrogen signaling also plays a role in male reproductive development (Sathyanarayana et al, 2012;Schwartz et al, 2019b;Stewart et al, 2018) beyond its role in mouse penile development (Govers et al, 2019;Zheng et al, 2015). This warrants further studies on the possible consequences of flusilazole-induced lower estrogen levels in male fetuses.…”

On the Use and Interpretation of Areola/Nipple Retention as a Biomarker for Anti-androgenic Effects in Rat Toxicity Studies

“…Interestingly, studies with BPA and butyl paraben have both shown small, but significant, effects on AGD ( Christiansen et al, 2014 ; Boberg et al, 2016 ), which could suggest that AGD, and not NR, may be regulated by an androgen-estrogen balance, perhaps similarly to what is the case for the genital tubercle which is sensitive to estrogen-androgen balance ( Yucel et al, 2003 ; Yang et al, 2010 ; Mattiske and Pask 2021 ). Indeed, studies have shown that the perineal tissues express the estrogen receptor (ER) ( Dionne et al, 1979 ; Schwartz et al, 2019b ) and one study shows that polymorphisms in the gene encoding the ER are associated with short AGD in human boys ( Sathyanarayana et al, 2012 ). This might suggest that AGD is a more sensitive endpoint than NR for chemicals with an estrogenic mode of action.…”