title: Effect of cisplatin on rat placenta development.
abstract: We examined the sequential histopathological changes in the placenta from rats exposed to cisplatin. Cisplatin was intraperitoneally administered at 2 mg/kg/day during GDs 11-12 (GD11,12-treated group), or GDs 13-14 (GD13,14-treated group), and the placentas were sampled on GDs 13, 15, 17 and 21. Fetal mortality rates were increased up to approximately 65% from GD 17 onward, and fetal weights were decreased on GD 21 in the GD11,12-treated group. A reduction in placental weights was detected from GD 15 onward, and the placentas on GD 21 were macroscopically small and thin in both treated groups. Histopathologically, in the GD13,14-treated group, an increase in apoptotic cells was detected on GDs 15 and 17 in the labyrinth zone, and on GD 21 in the basal zone, resulting in labyrinth zone hypoplasia. By contrast, in the GD11,12-treated group, an increase in apoptotic cells was detected on GDs 13, 15 and 17 in the labyrinth zone, and during the experimental period in the basal zone. A decrease in Phospho-Histone H3 positive cells was detected on GD 13 in the labyrinth zone and basal zone, resulting in hypoplasia of the labyrinth zone and basal zone. In addition, a marked decrease in glycogen cell-islands in the basal zone was also detected on GDs 15 and 17. There was a reduction in interstitial invasion of glycogen cell-like trophoblasts into the metrial gland on GD 15, resulting in metrial gland hypoplasia. Therefore, we consider that cisplatin administration in pregnant rats induces growth arrest of the labyrinth zone and basal zone, leading to small placenta. It is assumed that metrial gland hypoplasia is secondarily induced by the failure of glycogen cell island development associated with basal zone hypoplasia.
authors.affiliation: Toxicology & Environmental Science Department, Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan. furukawa@nissanchem.co.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Furukawa
authors.forename: Seigo
authors.initials: S
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Usuda
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Abe
authors.forename: Souichiro
authors.initials: S
authors.lastname: Hagio
authors.forename: Izumi
authors.initials: I
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D046689:Fetal Mortality / Q000639:trends; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018811:Maternal Exposure / Q000009:adverse effects; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000473:pathology*; D010929:Placentation; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin