Chromosomal aberration in the post-implantation embryos sired by tamoxifen treated male rats.
Tamoxifen is a synthetic non-steroidal Selective Estrogen Receptor Modulator used in the treatment of breast cancer and in treatment of male fertility. Earlier studies from our laboratory had demonstrated an increase in post-implantation embryo loss following tamoxifen treatment to adult male rats at a dose of 0.4mg/kg/day for 60 days. The post-implantation loss occurred at around 9-10 days of gestation suggesting that paternal factors involved in embryo development were affected by tamoxifen treatment. The present study was done to determine if any chromosomal aberrations occurred in the embryos sired by tamoxifen treated male rats. Chromosomal aberrations induced by tamoxifen treatment to adult male rats in the bone marrow (F(0) males) and in the embryos sired by these males (F(1) progeny) were determined. In addition, the reproductive performance of the F(1) progeny was assessed. A significant dose dependent reduction in mitotic activity in the bone marrow and embryonic cells was observed after tamoxifen treatment. In addition, tamoxifen also induced a significant dose dependent increase in the frequency of chromosomal aberrations, mainly gaps and breaks in bone marrow and embryonic cells. However, the embryos sired by the tamoxifen treated males had no effect on developmental milestones achieved and on their reproductive performance. The present study suggests that chromosomal aberrations observed in the embryos did not the affect their development until adulthood but could make the progeny of the tamoxifen treated males vulnerable to the development of adult onset diseases later in life.
Kedia-Mokashi
Neelam
N
Division of Neuroendocrinology, National Institute for Research in Reproductive Health (ICMR), Parel, Mumbai 400012, India.
Makawy
Aida E L
AE
Saxena
Madhurima
M
Balasinor
N H
NH
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D008297:Male; D018812:Paternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013629:Tamoxifen / Q000633:toxicity*
D004965:Estrogen Antagonists; D013629:Tamoxifen