Transcriptional activity of oestrogen receptors in the course of embryo development

Abstract

Oestrogens are well-known proliferation and differentiation factors that play an essential role in the correct development of sex-related organs and behaviour in mammals. With the use of the ERE-Luc reporter mouse model, we show herein that throughout mouse development, oestrogen receptors (ERs) are active starting from day 12 post conception. Most interestingly, we show that prenatal luciferase expression in each organ is proportionally different in relation to the germ layer of the origin. The luciferase content is highest in ectoderm-derived organs (such as brain and skin) and is lowest in endoderm-derived organs (such as liver, lung, thymus and intestine). Consistent with the testosterone surge occurring in male mice at the end of pregnancy, in the first 2 days after birth, we observed a significant increase in the luciferase content in several organs, including the liver, bone, gonads and hindbrain. The results of the present study show a widespread transcriptional activity of ERs in developing embryos, pointing to the potential contribution of these receptors in the development of non-reproductive as well as reproductive organs. Consequently, the findings reported here might be relevant in explaining the significant differences in male and female physiopathology reported by a growing number of studies and may underline the necessity for more systematic analyses aimed at the identification of the prenatal effects of drugs interfering with ER signalling, such as aromatase inhibitors or endocrine disrupter chemicals.

Estrogen Receptor β as a Candidate Regulator of Sex Differences in the Maternal Immune Activation Model of ASD

“…These effects were dependent on sex chromosome complement ( Cisternas et al, 2017 ). Activity of ERs, using an ERE-luciferase reporter, was observed in the fetal forebrain and hindbrain as early as E13.5, though no difference was detected between brains from females and males except in the P1 hindbrain ( Della Torre et al, 2018 ). Several key enzymes involved in steroid hormone synthesis are expressed in female and male E16 fetal brain, including StAR, Cyp11a1, 5α-Reductase, and aromatase ( Cisternas et al, 2015 ).…”

Application of Transgenic Zebrafish Models for Studying the Effects of Estrogenic Endocrine Disrupting Chemicals on Embryonic Brain Development

“…Estrogen responsive element (ERE)-luciferase transgenic mice have further evidenced the importance of estrogen signalling in embryonic brain development. In this model, the ER-mediated transcriptional activation was observed predominantly in the ectodermal organs (i.e., the brain and the skin) from stage E12.5, while very little ER-activity was detected in other germ layer derived organs at the same prenatal stage ( Della Torre et al, 2018 ). There was no apparent difference in such ectodermal ERE-luciferase activity in male or female at prenatal stage.…”

Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism

“…As such, the molecular machinery for sex-steroid action is present during fetal and neonatal development. ARs are expressed in the human fetal liver [ 169 ], and ER expression displays sex-specific differences in the mouse liver late in gestation and during neonatal life [ 162 , 163 ]. Additionally, estrogen signaling in white adipose progenitors inhibit differentiation into brown adipose [ 164 ], further suggesting that estrogen action during early development can induce organizational changes in adipose tissue in a sex-dependent manner.…”