Effects of cadmium on the expression of placental lactogens and Pit-1 genes in the rat placental trophoblast cells.

Cadmium is an endocrine disrupter (ED) with detrimental effects on mammalian reproduction. The placenta is a primary target for cadmium toxicity during pregnancy. Very little of this metal crosses the placenta to the fetus, and consequently it accumulates in high concentrations in the placenta. Cadmium affects on steroid synthesis and has estrogen- and androgen-like activities. In this study, we investigated the toxic effects of cadmium on placental trophoblast cells as well as the mRNA levels of placental lactogens (PLs), which are under the control of estrogen and play a pivotal role during pregnancy. Pregnant F344 Fisher rats were injected subcutaneously with 0, 0.2, and 2.0mg/kg BW/day of cadmium (CdCl(2)) dissolved in saline from days 11 to 19 of pregnancy and were sacrificed on day 20. The mRNA levels of the PL-Iv and -II genes and Pit-1alpha and beta isotype genes, the trans-acting factor of PLs, were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction, respectively. The frequency of the placental trophoblast cells was observed histochemically. Developmental data and apoptotic chromosomal DNA fragmentation of placental cells were also observed. The mRNA levels of PL-Iv and -II were reduced in a dose-dependent manner by cadmium. The mRNA levels of the Pit-1alpha and beta isotype genes were also reduced by cadmium. In the uterus-conjugated region of the placental junctional zone, the frequency rates of trophoblast cells were lower in the cadmium-treated groups than in the control group. High-dose cadmium exposure (2.0mg) induced not only the reduction of trophoblast cell frequency but also apoptotic chromosomal DNA fragmentation in the junctional zone of the placenta. Developmental metrics such as placental and fetal weights and a number of live fetuses, decreased, while a numbers of resorptions, dead fetuses, and post-implantation losses increased significantly (p<0.05) in the cadmium-treated groups compared to the control. These data suggested that cadmium inhibits the expression of PL genes and reduces the number of trophoblast cells in the rat placenta via an estrogen-like activity, leading to significant toxic effects on placental growth and physiological function in rats.

Effects of manganese exposure on dopamine and prolactin production in rat.

Although manganese (Mn) has been shown to increase prolactin (PRL) by decreasing dopamine (DA) in the hypothalamus, the mechanism of Mn-induced regulation of the hypothalamic-hypophyseal-pituitary axis is unclear. We assessed the effects of inhaled Mn on hypothalamic DA and pituitary PRL production and evaluated the role of pituitary-specific transacting factor 1 (Pit-1), a transacting factor of PRL gene, in Mn-induced changes in PRL secretion in the rat brain. Male rats exposed to Mn for 4 or 13 weeks (1.5 mg/m3, 6 h/day, 5 days/week) showed a progressive and significant decrease in hypothalamic DA, whereas PRL and Pit-1 mRNA levels increased in response to Mn exposure. These results suggest that exposure to Mn decreases hypothalamic DA and promotes the production of PRL in the pituitary and that Pit-1 might be a regulator of DA and PRL.

[Effects of bisphenol A on the placental function and reproduction in rats].

OBJECTIVES: The aim of this study was to investigate the effects of bisphenol A (BPA), an estrogen-like environmental endocrine disrupter, on the placental function and reproduction in rats. The mRNA levels of the placental prolactin-growth hormone(PRL-GH) gene family, placental trophoblast cell frequency and reproductive data were analyzed. METHODS: The pregnancies of F344 Fisher rats (160 g +/-20 g) were detected by the presence of the copulatory plug or sperm in the vaginal smear, which marked Day 0 of pregnancy. Pregnant rats were divided into three groups. The control group was intraperitoneally injected with a sesame oil vehicle. The two remaining groups were injected with 50 or 500 mg/kg B.W/day of BPA, resuspended in sesame oil, on either days 7 to 11 or 16 to 20 of pregnancy, with the rats sacrificed on either day 11 or 20, respectively. The mRNA levels of PRL-GH and Pit-1a and b isotype genes were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction. The hormone concentrations were analyzed by radioimmunoassay, and the frequency of the placental trophoblast cells observed by a histochemical study. Reproductive data, such as the placental weight and litter size, were surveyed on day 20. The fetal weight was surveyed for 4 weeks after birth. A statistical analysis was carried out using the SAS program (version 8.1). RESULTS: The mRNA levels of the PRL-GH gene family, such as placental lactogen I, Iv and II, prolactin like protein A, C and Cv, and decidual prolactin-related protein were significantly reduced due to BPA exposure. The mRNA levels of the Pit-1a and b isotype genes, which induce the expression of the PRL-GH gene family in the rat placenta, were also reduced due to BPA exposure. The PL-Iv and PL-II concentrations were reduced in the BPA exposed group. During the middle to last stage of pregnancy (Days 11-20), a high dose of BPA exposure reduced the frequency of spongiotrophoblast cells, which are responsible for the secretion of the PRL-GH hormones. Reproductive data, such as the placental and fetal weights and the litter size, were reduced, but that of the pregnancy period was extended in the BPA exposed compared to the control group. CONCLUSIONS: BPA disrupts the placental functions in rats, which leads to reproductive disorders.

Effects of Aroclor 1254 on the expression of rat placental PRL-family genes.

This study was performed to investigate the effects of Aroclor 1254 (A1254), a commercial polychlorinated biphenyl mixture, on the expression of rat placental prolactin (PRL) family genes and reproductive activity. Placental lactogen-Iv and -II, and prolactin-like protein-A and -C mRNA levels were significantly decreased in the placentas of A1254-treated rats in a dose-dependent manner. The mRNA levels of Pit-1alpha and beta isotypes, which are involved in the regulation of PRL family gene expression, were also decreased in the A1254-treated rat placenta. In the rat placental junctional zone, high-dose A1254 (25 mg/kg B.W.) treatment reduced the number of spongiotrophoblasts, cells in which the PRL family genes are expressed. Finally, maternal exposure to A1254 was shown to have significant toxic effects on reproductive activity, including embryonic and placental growth retardation, delay of parturition, and reduction of the number of pups per litter. The results of the present study indicated that A1254 has an inhibitory effect on PRL family, Pit-1alpha, and beta gene expression in the rat placenta, leading to significant toxic effects on reproductive activity in rats.