“…Their expression and transcriptional activity in the course of embryo development is less studied (Brandenberger et al 1997; Lemmen et al 1999). In addition to selective KO mutation of ERα, ERβ, or the aromatase gene ( Cyp19a1 , encoding the enzyme responsible for testosterone-derived oestrogen synthesis) that highlighted the relevance of these receptors and their cognate ligands for the development of sexual organs and sexual behaviour (Kudwa, et al 2006), the elucidation of the ER distribution and activity during implantation and embryogenesis in non-reproductive tissues is circumscribed to only a few studies (Bondesson, et al 2015; Mogi, et al 2015; Park, et al 2017). However, preclinical and clinical observations in subjects carrying mutations that impair ER signalling showed deviations from the proper development of the cardiovascular system (Del Principe, et al 2015; Tait et al 2015), innate immune and neuro-immune communications (Zoller and Kersh 2006), pancreatic and gastric activity (Campbell-Thompson, et al 2001; Maniu, et al 2016), and liver functions (Barros and Gustafsson 2011; Bryzgalova, et al 2006; Foryst-Ludwig, et al 2008), as well as adipose (Barros and Gustafsson 2011; Lapid et al 2014), lung (Carey, et al 2007; Patrone, et al 2003; Thuresson-Klein et al 1985), kidney (Kummer, et al 2011; Lane 2008), and epidermal tissues with the muscle-skeletal apparatus (Brandenberger et al 1997; Hanley et al 1996; Lemmen et al 1999; Markiewicz, et al 2013; Takeyama et al 2001; Ueberschlag-Pitiot, et al 2017; Walker and Korach 2004).…”