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Estrogens play a role in sence of smell - A study carried out in Fish

According to new research, steroid estrogens play a crucial function in the development of a sense of smell in embryos.

The study, which looked at zebrafish embryos, revealed a brand-new form of astrocyte glial cell called oestrogen responsive olfactory bulb (EROB) cells.

Estrogens are well-known for their involvement as signalling hormones in the formation of sex, but a new study demonstrates that oestrogen can affect a tiny group of cells in the olfactory bulb, which develops the sense of smell, before sexual differentiation (when an individual's sex becomes fixed).

Dr. Aya Takesono of the University of Exeter led the study, which used a genetically altered (transgenic) zebrafish generated in Professor Tyler's and Dr. Kudoh's laboratory at Exeter to see cells and tissues responding to oestrogen via microscope imaging.

The use of transgenic zebrafish, as well as pharmacological and genetic approaches to modify estrogen-responsive cells, has shown a novel role for estrogens during embryonic brain development.

"Previous research in mice have revealed that oestrogen is critical for the development of the sensorimotor cortex of the brain, as well as the establishment of sexual dimorphic brain structures that mediate reproductive activities and behaviour later in life," Dr Takesono stated.

"In this study, however, we show that the olfactory bulb is one of the first areas of the developing brain in the zebrafish embryo to respond to estrogens."

"We also show that our recently found EROB cells mediate estrogen-driven olfactory sensory system development in the embryonic brain."

Using various cellular and imaging methods to track the development of these EROBs, researchers discovered that they interact with olfactory sensory neurons, and that their loss — or disruption of their interactions with the surrounding neurons — disrupts the establishment of inhibitory neural connections in the olfactory glomeruli.

The study shows that oestrogen signalling alters neuronal activity in the olfactory bulb through these newly identified EROBs, which in turn affects odorant-response behaviour, using another transgenic zebrafish that detects both neural activity (via the detection of calcium produced when nerve cells fire) and oestrogen responses.

This research shows that estrogens modulate olfactory circuits by acting on EROB glia, which has crucial implications for the sense of smell in later life.

"This work discovering new embryonic brain cells involved in the development of the sense of smell in fish opens up a big new research avenue for us," said Professor Tyler, the study's senior author.

"Many human-made chemicals that mimic estrogens are found in surface waters, and an intriguing question we'd like to investigate now is whether these chemicals affect the function of the EROB glia in embryogenesis, thereby altering the sense of smell, as this could have major fitness implications for fish."

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