Carbenoxolone exposure during late gestation in rats alters placental expressions of p53 and estrogen receptors.
Gestational carbenoxolone exposure inhibits placental 11β-hydroxysteroid dehydrogenase (11β-HSD), the physiological barrier for glucocorticoids, which increases fetal exposure to glucocorticoids and induces intrauterine growth restriction (IUGR). We hypothesized that carbenoxolone exposure influences the expression of placental estrogen receptors-α and β (ERα & ERβ) and p53 leading to inhibited fetal and placental growth. Pregnant Sprague-Dawley rats were injected twice daily with either carbenoxolone (10mg/kg; s.c.) or vehicle (control group) from gestational days (dg) 12 onwards. Maternal blood and placentas were collected on 16 dg, 19 dg and 21 dg. The expression of ERα, ERβ and p53 were studied in placental basal and labyrinth zones by RT-PCR, Western blotting and immunohistochemistry. Carbenoxolone did not affect placental and fetal body weights, but ELISA showed decreased estradiol levels on 19 dg and 21 dg, and increased maternal luteinizing hormone levels on all dg. The follicle stimulating hormone levels decreased on 16 dg and 19 dg, and increased on 21 dg. Carbenoxolone decreased ERα mRNA levels on 16 dg in both zones and its protein level on 19 dg in the labyrinth zone. However, carbenoxolone increased ERβ mRNA levels on 19 dg and 21 dg and protein levels on 16 dg and 19 dg in the labyrinth zone. The p53 mRNA levels increased on all dg, but its protein levels increased on 21 dg in both zones. In conclusion, carbenoxolone exposure changes placental p53, ERα, ERβ expression in favor of cell death but these changes do not induce IUGR in rats.
Department of Physiology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: albader@hsc.edu.kw.
Maie D
MD
Al-Bader
Department of Physiology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: sarahajasem@gmail.com.
Sara A
SA
Jasem
Department of Anatomy, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Electronic address: knarayana@hsc.edu.kw.
Narayana
N
Kilarkaje
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002229:Carbenoxolone / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009035:Mothers; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D016159:Tumor Suppressor Protein p53; D002229:Carbenoxolone
Apoptosis; Carbenoxolone; Estrogen receptor; Intrauterine growth restriction; P53