Lactational coumestrol exposure increases ovarian apoptosis in adult rats.
This study is the first to examine the increased apoptosis in the adult rat ovary after lactational exposure to coumestrol (COU), a potent phytoestrogen. Lactating dams were gavaged at doses of 0.01, 0.1, 1, and 10 mg/kg COU during the lactation period and the reproductive effects of female pups were investigated in young adults. Rats were sacrificed at postnatal days (PND) 81-84. Ovarian weights were reduced significantly at 0.1 and 1.0 mg/kg COU. The reduction in the ovarian weight occurred in parallel with an increase in the apoptosis at PND 135-140. A marked dose-dependent increase in the expressions of active caspase-3 and -7 was observed in ovarian granulosa cells. Immunostaining for active caspase-3 and the TUNEL staining of apoptotic cells were also increased in ovaries exposed to COU in a dose-dependent manner. These results suggest new sights into the effect of lactational exposure to COU on the female reproductive health.
Moon
Hyun-Ju
HJ
Reproductive and Developmental Toxicology Division, National Institute of Toxicological Research, Korea Food and Drug Administration, 194 Tongil-ro, Eunpyung-gu, Seoul 122-704, South Korea. mhj1612@kfda.go.kr
Seok
Ji Hyun
JH
Kim
Soon Sun
SS
Rhee
Gyu Seek
GS
Lee
Rhee Da
RD
Yang
Jun Young
JY
Chae
Soo Yeong
SY
Kim
Seung Hee
SH
Kim
Ji Young
JY
Chung
Jin-Yong
JY
Kim
Jong-Min
JM
Chung
Soo Youn
SY
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D003375:Coumestrol / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects
D048789:Phytoestrogens; D053148:Caspase 3; D053179:Caspase 7; D003375:Coumestrol