Developmental effects: oestrogen-induced vaginal changes and organotin-induced adipogenesis

Area of Science:

• Endocrinology
• Developmental Biology
• Environmental Health

Background:

• The fetal origin of adult disease paradigm highlights how early-life exposures impact long-term health.
• Prenatal exposure to endocrine-disrupting compounds (EDCs) like diethylstilbestrol (DES) causes reproductive abnormalities (DES syndrome).
• Environmental contaminants like tributyltin chloride (TBT) are known to disrupt development.

Purpose of the Study:

• To investigate the effects of developmental exposure to endocrine disruptors on health.
• To explore the mechanisms by which estrogenic compounds and TBT alter developmental programming.
• To establish TBT as an EDC with effects across species.

Main Methods:

• Examined persistent proliferation of vaginal epithelial cells in mice neonatally exposed to estrogens.
• Investigated molecular mechanisms including receptor phosphorylation and growth factor expression.
• Assessed TBT's effects on adipocyte differentiation in vitro and adipose mass in vivo in vertebrates.
• Determined TBT's ligand affinity for retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ).
• Analyzed lipid accumulation in various tissues following in utero TBT exposure in mice and ectopic adipocyte formation in Xenopus laevis.

Main Results:

• Developmental estrogen exposure induces persistent vaginal epithelial cell proliferation via molecular signaling pathways.
• TBT promotes adipogenesis by activating RXRα and PPARγ, leading to increased adipose mass and lipid accumulation in multiple organs.
• TBT exposure in utero results in elevated lipid accumulation in adipose depots, liver, and testes of neonate mice.
• Ectopic adipocytes form in gonadal tissues of Xenopus laevis after organotin exposure.
• TBT demonstrates adverse effects across species from gastropods to mammals.

Conclusions:

• Prenatal and early postnatal exposures to endocrine-disrupting compounds permanently alter developmental programming.
• Estrogenic compounds and TBT serve as strong examples of EDCs with lasting impacts on health.
• TBT is the first identified environmental EDC to cause adverse effects from invertebrates to mammals, highlighting its broad biological activity and potential human health risks.