TY - JOUR
T1 - Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus
AU - Topper, Viktoria Y.
AU - Walker, Deena M.
AU - Gore, Andrea C.
N1 - Funding Information:
Funding was provided by NIH grants RO1 ES020662 and RO1 ES023254 to ACG, and F31 AG034813 to DMW. The authors have nothing to disclose.
Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/10/5
Y1 - 2015/10/5
N2 - This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.
AB - This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.
KW - Endocrine-disrupting chemicals (EDCs)
KW - Hypothalamus
KW - Medial preoptic nucleus (MPN)
KW - MicroRNA
KW - Polychlorinated biphenyls (PCBs)
KW - Ventromedial nucleus (VMN)
UR - http://www.scopus.com/inward/record.url?scp=84938053663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938053663&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2015.07.013
DO - 10.1016/j.mce.2015.07.013
M3 - Article
C2 - 26190835
AN - SCOPUS:84938053663
SN - 0303-7207
VL - 414
SP - 42
EP - 52
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -