Effect of paternal tamoxifen on the expression of insulin-like growth factor 2 and insulin-like growth factor type 1 receptor in the post-implantation rat embryos.
Nuclear transplantation studies demonstrated the importance of paternal contribution to embryogenesis. Paternal treatment with agents like cyclophosphamide and 5-azacytidine has been shown to cause an increase in pre-implantation loss (PIL) and post-implantation loss (POL). Studies from our laboratory have shown that paternal tamoxifen treatment increases PIL and POL. It was observed that the PIL occurred at day 2 of gestation (embryo at 2-4 cell stage) and the POL occurred around day 9 of gestation (mid-gestation). The insulin-like growth factor (IGF) system represents one of the major growth-controlling system expressed in the embryo. Several studies suggest that in rodents, insulin-like growth factor 2 (Igf2) signaling through the insulin-like growth factor type 1 receptor (Igf1r) modulates embryo growth at around days 9-11 of gestation (mid-gestation). The present study was undertaken to evaluate the expression of Igf2 and Igf1r transcript by RT-PCR in the post-implantation embryos obtained after paternal tamoxifen treatment. It was observed that both the genes were down regulated in resorbed embryos (POL). Since Igf2 is an imprinted gene and the imprint mark is established during spermatogenesis, the present study suggests that paternal tamoxifen treatment may have affected imprinting of the gene during spermatogenesis thereby decreasing its expression and leading to increase in POL. This is to our knowledge the first study correlating the increase in post-implantation embryo loss obtained after paternal drug treatment with the decrease in the expression of Igf2 in these embryos.
Division of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Parel, Mumbai 400 012, India.
Neelam
N
Kedia
Manjit K
MK
Gill-Sharma
Priyanka
P
Parte
Harbans S
HS
Juneja
Nafisa
N
Balasinor
D000818:Animals; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D018812:Paternal Exposure; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1