| Early-life experiences are known to shape brain development, influencing later physiological and behavioural responses to stress. To investigate this, three experiments were conducted to show that in female mice, the neonatal manipulations of brief (H 15 mins/day) or prolonged (MS 4 hrs/day) maternal separation during the first three weeks of life can influence adulthood anxiety-like behaviour, stress hormone physiology, mammary gland development and carcinogen-induced mammary tumor risk. In early adulthood, female MS mice showed increased anxiety-like behaviour, low basal corticosterone levels and amplified corticosterone responses to stress. Interactions between glucocorticoids and circulating reproductive hormones could have influenced mammary gland development, as early mammary gland maturation was observed in adult H and MS mice compared to non-separated typically reared (TR) mice. Young adult MS mice had increased mammary gland expression of ERalpha protein (but not mRNA) and Brms1 mRNA (both breast cancer risk factors), and decreased expression of ERbeta and Tgfbeta2 mRNA (breast cancer protective factors). These molecular and morphological changes could have contributed to the increased mammary tumor incidence observed in MS mice after early adulthood carcinogen administration. These findings suggest that adverse early-life experiences can increase mammary tumor risk through hormone-mediated alterations in mammary gland development.Keywords: Cancer etiology, neonatal-maternal interactions, mammary gland development, gene-environment interactions, anxiety-like behaviour. |
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