Transplacental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats

Female ACI rats were exposed to diethylstilbestrol (DES) transplacentally and followed to 10 months of age to assess the effect of the drug on mammary development and tumorigenesis. Pregnant rats were given injections of vehicle (sesame oil) or DES (total dose, 0.8 micrograms = low DES or 8.0 micrograms = high DES) on days 15 and 18 of gestation. Pellets containing 2.5 mg DES + 17.5 mg cholesterol (DES pellet) or 20 mg cholesterol (chol pellet) were implanted s.c. into 12-week-old female offspring, creating 6 experimental groups: vehicle exposure + chol pellet (1) or + DES pellet (2); low DES exposure + chol pellet (3) or + DES pellet (4); high DES exposure + chol pellet (5) or + DES pellet (6). At sacrifice, representative mammary tissue and all palpable mammary tumors were removed for histopathological analysis. Each of the 6 experimental groups contained a minimum of 32 rats from at least 14 litters. In computation of data, the unit of analysis was the litter. Groups which had received any DES (prenatally or postnatally) were found to have elongated nipples and enlarged pituitaries. The mammary gland whole mounts from all rats in groups 4 and 6 displayed extensive lobuloalveolar proliferation comparable to that seen in DES pellet controls (group 2). Mammary glands of approximately 75% of rats in groups 3 and 5 were categorized as showing the lowest grade of differentiation while this undifferentiated condition was seen in only 36% of group I controls. No palpable mammary tumors were found in rats exposed to vehicle in utero (group 1). But in group 5, a total of 6 tumors in 5 animals derived from 4 different litters were obtained, a difference shown to be statistically significant. Group 3 had 1 rat with 8 tumors. Among rats bearing the DES pellet, tumor latency was shortened significantly in both groups exposed to DES in utero. By 22 weeks after pellet implantation, 100% of the DES-exposed litters (groups 4 and 6) contained at least 1 tumor-bearing rat compared to about 50% of the tumor-bearing litters in group 2. Tumor multiplicity at sacrifice was increased significantly in the group exposed prenatally to the higher dose of DES. Histologically, the overwhelming majority of palpable mammary tumors from all tumor-bearing treatment groups were classified as adenocarcinomas. Prenatal exposure to DES did not alter the ratio of malignant to benign lesions observed, nor did it affect the degree of differentiation noted in the adenocarcinomas.(ABSTRACT TRUNCATED AT 400 WORDS)     

已烯雌酚致新生鼠肺肿瘤模型的建立

Objective： To explore a economical and effective method for building lung tumor model induced by diethylstibestrol （DES）. Methods： The carcinogenic effect of neonatal mice treated by DES was studied. The newborn mice were divided into DES, Urethan （U） and U ＋ DES groups. U group was given in 500 mg/kg dose by ip at postnatal 14 day, DES group was administered by ip at the 1 d, 8 d, 15 d in the dose of 1/7, 2/7 and 4/7 LD50 of the day when they were injected respectively for DES （I）, DES （M）, DES （H） groups. Until 26 weeks, they were anatomized and checked the formation of tumors. The organ index, tumor incidence ratio and mean number of tumors were calculated. Results： Lung tumors were apparently induced in tested neonatal mice. The incidence of lung tumor of DES （L, M, H） groups were 16.7%, 22.4% and 43.1% respectively, the U ＋ DES （L, M, H） groups were 70.4%, 90.9% and 70.8% respectively, and the U group was 53.1%. The mean numbers of lung tumors of U ＋ DES （L, M） groups were higher than those of the DES （L, M） groups respectively （P 〈 0.05）. Conclusion： The higher ratio of lung tumor incidence had been induced by DES and U joined action to neonatal mice, which may be a useful and economical method to establish a lung tumor model induced by DES.     

Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.     

Cancer risk in women prenatally exposed to diethylstilbestrol

Prenatal diethylstilbestrol (DES) exposure is associated with excess risks of clear cell adenocarcinoma (CCA), and breast cancer in older women. Whether overall cancer risk is also elevated is unclear. Total and site-specific cancer risks were evaluated in the DES Combined Cohort Follow-up Study using age- and calendar-year specific standardized incidence rate ratios (SIR), and age-adjusted incidence rate ratios (RR) comparing DES exposed and unexposed women. A total of 143 and 49 cancer cases occurred in 97,831 and 34,810 person-years among the exposed and unexposed, respectively. There was no overall excess risk among exposed women when compared with external rates (SIR 1.01; 95% confidence interval [CI] 0.86-1.2). The overall RR comparing exposed with unexposed women was 1.32 (95% CI 0.94-1.8). Breast cancer risk was elevated only among women over 40 years (RR 1.83; 95% CI 1.1-3.2). The CCA SIR among exposed women was nearly 40, and the estimated attack rate through age 39 was 1.6/1,000 women. CCA incidence decreased by over 80% after age 25 when compared with 20-24 years. Excluding CCA and breast cancer, the overall RR was 1.21 (95% CI 0.74-2.0). DES was not associated with excess risks of either endometrial or ovarian cancer. These data suggest that the DES associated increase in CCA incidence remains elevated through the reproductive years. There was no consistent evidence of risk excesses for cancers other than CCA, and breast cancer in older women. Given that the population is still young, continued follow-up is necessary to assess the overall carcinogenic impact of prenatal DES exposure.     

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.     

Transplacental action of diethylstilbestrol on mammary carcinogenesis in female rats given one or two doses of 7,12-dimethylbenz(a)anthracene

Aspects of the development, morphology, and estrogen binding capacity of mammary tumors in rats exposed prenatally to the synthetic estrogen, diethylstilbestrol (DES), and treated postnatally with 7,12-dimethylbenz(a)anthracene (DMBA) were analyzed as part of a project aimed at understanding the effects of transplacental exposure to DES on estrogen-sensitive tissues. Pregnant Sprague-Dawley rats were given injections of DES (total dose, 1.2 micrograms) or vehicle alone on Days 15 and 18 of gestation. All female offspring were given gastric intubations of DMBA, either a single 10-mg dose on Day 50 or two doses (10 mg each) on Days 50 and 57. Among rats treated postnatally with 10 mg of DMBA, the DES-exposed group had a significantly greater incidence of palpable mammary tumors than did the vehicle-exposed controls. In addition, there was an earlier time of appearance of palpable tumors in the DES-exposed group. When the data from rats treated postnatally with two 10-mg doses of DMBA were analyzed, there were no significant differences in palpable mammary tumor incidence or tumor latency between the DES-exposed and vehicle-exposed groups. When the pathology of the mammary tumors produced in rats treated with 10 mg of DMBA was analyzed, the DES-exposed group had a significantly higher proportion of benign tumors (fibroadenoma, adenoma, lobular hyperplasia) than adenocarcinomata compared to vehicle-exposed controls. Both exposure groups had similar numbers of nonpalpable mammary lesions discovered at necropsy. Estrogen binding capacities of representative adenocarcinomata did not differ significantly between the two prenatal exposure groups treated postnatally with 10 mg of DMBA. These results demonstrate the importance of the dose of the challenge carcinogen in revealing the effects of transplacental drug exposure and may have special significance for women who were exposed to DES in utero.     

Randomized trial of diethylstilbestrol vs. tamoxifen in postmenopausal women with metastatic breast cancer. An updated analysis

One hundred fiftyone postmenopausal women with progressive metastatic breast cancer and no prior hormonal therapy were treated with either diethylstilbestrol (DES) or tamoxifen (TAM). One hundred fortythree eligible patients were followed until death or for a minimum of 14.1 years on the DES arm or 16.7 years on the TAM arm. The overall objective response was 42% for DES and 33% for TAM (p=0.31) and the median duration of response was 11.8 months for DES and 9.9 months for TAM (p=0.38). Duration of response and progressionfree survival were not found to be significantly different between DES and TAM (p=0.32 and 0.65, respectively). The median survival was 3.0 years for DES vs. 2.4 years for TAM. The 5year survival was 35% for the DES arm and 16% for the TAM arm. Survival was significantly better for women on DES than for women on TAM (adjusted p=0.039). Review of records did not show any difference in pattern of treatment failure or subsequent treatments in the DES and TAM arms.Treatment with DES was more commonly associated with toxicity such as nausea, edema, vaginal bleeding, and cardiac problems, whereas hot flashes were commonly seen with TAM therapy.The initial treatment with DES is associated with increased survival. The basis of this survival advantage is not known. TAM still is the preferred agent in the treatment of metastatic breast cancer, but this trial underscores the fact that estrogens have activity and remain in the armamentarium for treatment of selected patients with metastatic breast cancer.     

Induction of hepatic tumors by diethylstilbestrol in N-nitrosobutylurea-initiated female rats

The carcinogenic effect of estrogens, diethylstilbestrol (DES) and 17 beta-estradiol (E2), and its modification by N-nitrosobutylurea (NBU) were studied in female W/Fu rats. Multiple mammary tumors (MT) of medullary carcinoma type developed at a high rate following prolonged treatment with estrogens. All MTs were located adjacent to the nipple and were slow-growing. The induction rate, multiplicity and size of estrogen-induced MTs were not influenced by pretreatment with a small amount of NBU, which alone did not induce any tumor. Ten of 12 rats (82%) receiving combined treatment with NBU and DES developed hepatic tumors (HT), while no rats in other treatment groups developed HT. All HTs were multiple nodules of various sizes bulging from the liver surface, and were considered to be neoplastic nodules. A high frequency of HT development was unexpected, because independent treatment with NBU or DES alone did not induce HT in female rats. It appears that DES played a role as a carcinogen, inducing MT and pituitary tumor (PT) through its estrogenic potency (like natural estrogen, E2), while it also acted as a promoter or co-carcinogen in the induction of HT through its pharmacologic effects. These findings may be relevant to an increased frequency of liver neoplasm among women taking oral contraceptives containing synthetic estrogens.     

Insulin-like growth factor binding protein-6 inhibits prostate cancer cell proliferation: implication for anticancer effect of diethylstilbestrol in hormone refractory prostate cancer

Diethylstilbestrol (DES) is a synthetic oestrogen, and its anticancer effects are exerted in androgen-dependent prostate cancer. The administration of DES decreases serum testosterone to castration levels. However, in androgen-independent prostate cancer patients, who are already orchiectomised, the administration of DES improves symptoms and decreases prostate-specific antigen (PSA). The mechanisms responsible for these direct inhibitory effects have been explained as biological actions not mediated by oestrogen receptors. We assessed the gene expression profiles of prostate cancer cells treated with DES, and investigated direct inhibitory effects of DES. DES inhibited the proliferation of LNCaP and PC-3 cells. cDNA microarray analysis showed that expression of many genes was downregulated by DES. However, insulin-like growth factor binding protein 6 (IGFBP-6) gene expression levels were upregulated in PC-3 cells. IGFBP-6 gene expression and protein levels significantly increased after DES treatment. Recombinant IGFBP-6 inhibited cell proliferation, and the inhibitory effect of DES was neutralised by anti-IGFBP-6 antibody. From the immunohistochemical analysis of IGFBP-6 using biopsy samples from androgen-independent prostate cancer, we found IGFBP-6 expression in androgen independent prostate cancer, and that DES treatment increased the IGFBP-6 staining intensity of the cancer cells in one sample. These findings suggested that DES induces IGFBP-6, which inhibits cell proliferation in an androgen-independent prostate cancer cell line, PC-3. IGFBP-6 therefore might be involved in the direct effects of DES in androgen-independent prostate cancer.     

Synergism of diethylstilbestrol and radiation in mammary carcinogenesis in female F344 rats.

One compressed 20-mg pellet containing cholesterol only or cholesterol mixed with 0.98, 1.6, 2.6, or 3.9 mg of diethylstilbestrol (DES) was implanted into each of 203 female F344 rats. Two days later, half the animals in each group were exposed to 150 R of X-rays, and the other half were sham irradiated. The rats were maintained until 350 days post implantation. Mortality increased with the higher doses of DES, with or without X-rays. DES at all dose levels, with or without X-rays, produced pituitary tumors and pyometritis. Only rats that received both DES and X-rays had mammary adenocarcinomas (AC). A synergistic AC response was found in the group that received 2.6 mg DES plus X-rays. Synergism was defined as a significantly greater incidence of rats with mammary neoplasia resulting from DES plus X-ray treatment when compared to the summed incidence from comparable individual treatments. For all other groups of rats that received both treatments, synergism was detected only when their data were combined. Synergism was not detected among rats that had fibroadenomas (FA). Both types of neoplasms were independent phenomena because no significant relationship was found between the incidences of FA and AC.     

Mortality in women given diethylstilbestrol during pregnancy

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI = 1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03-1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES-cohort interaction was not significant (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses.     

Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: The defining link to natural estrogens

Diethylstilbestrol (DES) is a human carcinogen, based on sufficient epidemiological evidence. DES is mainly metabolized to its catechol, 3′‐hydroxyDES (3′‐OH‐DES), which can further oxidize to DES‐3′,4′‐quinone (DES‐3′,4′‐Q). Similarly to estradiol‐3,4‐quinone, the reaction of DES‐3′,4′‐Q with DNA would form the depurinating 3′‐OH‐DES‐6′‐N3Ade and 3′‐OH‐DES‐6′‐N7Gua adducts. To prove this hypothesis, synthesis of DES‐3′,4′‐Q by oxidation of 3′‐OH‐DES with Ag₂O was tried; this failed due to instantaneous formation of a spiro‐quinone. Oxidation of 3′‐OH‐DES by lactoperoxidase or tyrosinase in the presence of DNA led to the formation of 3′‐OH‐DES‐6′‐N3Ade and 3′‐OH‐DES‐6′‐N7Gua adducts. These adducts were tentatively identified by LC‐MS/MS as 3′‐OH‐DES‐6′‐N3Ade, m/z = 418 [M+H]⁺, and 3′‐OH‐DES‐6′‐N7Gua, m/z = 434 [M+H]⁺. Demonstration of their structures derived from their oxidation by MnO₂ to the DES quinone adducts and subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are identical to the standard 3′‐OH‐DIES‐6′‐N3Ade, m/z = 416 [M+H]⁺, and 3′‐OH‐DIES‐6′‐N7Gua, m/z = 432 [M+H]⁺, adducts. The reaction of DIES‐3′,4′‐Q or lactoperoxidase‐activated 3′‐OH‐DIES with DNA did not produce any depurinating adducts, due to the dienic chain being perpendicular to the phenyl planes, which impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3′‐OH‐DES suggests that the catechol of DES intercalates into DNA and is then oxidized to its quinone to yield N3Ade and N7Gua adducts. These results suggest that the common denominator of tumor initiation by the synthetic estrogen DES and the natural estrogen estradiol is formation of their catechol quinones, which react with DNA to afford the depurinating N3Ade and N7Gua adducts. © 2008 Wiley‐Liss, Inc.     

Risk of breast cancer in women exposed to diethylstilbestrol in utero: prelimiinary results (United States)

BACKGROUND: A synthetic estrogen, diethylstilbestrol (DES), was widely prescribed to pregnant women during the 1950s and 1960s but was later discovered to be associated with an increased risk of clear-cell carcinoma of the vagina and cervix in female offspring. DES has not been linked to other cancers in female offspring, but studies of other prenatal factors such as twin gestation and pre-eclampsia have indicated that in-utero estrogen levels may influence breast cancer risk. We evaluated the relation of in-utero DES exposure to the risk of adult breast cancer.METHODS: A cohort of 4821 exposed women and 2095 unexposed women, most of whom were first identified in the mid-1970s, were followed by mailed questionnaires for an average of 19 years. Reported cancer outcomes were validated by medical record review. Breast cancer incidence in DES-exposed daughters was compared with cancer incidence in unexposed daughters with use of Poisson regression analysis, adjusting for year of birth, age at menarche, age at first birth, and number of births.FINDINGS: The rate ratio for incidence of invasive breast cancer in exposed versus unexposed women was 1.4 (95% confidence interval (CI) = 0.7–2.6). DES exposure was not associated with an increased risk of breast cancer in women under 40 years, but among women aged 40 and older the rate ratio was 2.5 (95% CI = 1.0–6.3). The rate ratio for the association of DES exposure with estrogen receptor-positive tumors was 1.9 (95% CI = 0.8–4.5).INTERPRETATION: While not statistically significant, the overall 40% excess risk, arising exclusively from the subset of estrogen receptor-positive cases, raises a concern calling for continued investigation.     

Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States)

Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. Methods: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for 13 years (1982–1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2–3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4–5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.     

Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus

Perinatal exposure to diethylstilbestrol (DES) induces reproductive tract cancers later in life in both humans and animals. Because there is no clear evidence that perinatal DES exposure induces gene mutation, we proposed that perinatal DES exposure causes epigenetic methylation changes that result in persistent alterations in gene expression, leading to tumorigenesis. The proto-oncogene c-fos is one of the immediately induced genes in uterine epithelium after estrogen simulation and a key player in uterine carcinogenesis. Here, we investigated c-fos expression in mice neonatally exposed to DES (2 microg/pup/day on postnatal days 1-5). The mRNA levels of c-fos in uteri of neonatal DES-treated mice were persistently 1.4-1.9-fold higher than that in the control mice from day 5 to day 60. Overall, the uterine c-fos expression level in the neonatal DES-exposed group was significantly higher than that in the control group. After examination of the methylation status of the c-fos gene, we found that the CpGs in promoter and intron-1 regions were completely unmethylated. In exon-4, from day 17 to day 60, the percentage of unmethylated CpGs was higher in neonatal DES-exposed mice uteri than that in control (42%, 51%, 47%, and 42% in DES-exposed mice vs 33%, 34%, 33%, and 21% in control mice at day 17, 21, 30, and 60, respectively). These results suggest that perinatal DES exposure may permanently alter gene expression and methylation, and the methylation modification may occur in either the promoter regions or other regulatory sites in the gene.     

A validated prognostic index predicting response to dexamethasone and diethylstilbestrol in castrate‐resistant prostate cancer

BACKGROUND:

The objective of this study was to identify subgroups of patients with castrate‐resistant prostate cancer (CRPC) who had a prolonged response to combined dexamethasone and diethylstilbestrol (DS) therapy by constructing a prognostic index.

METHODS:

Multivariate and cutoff point analyses with bootstrapping were performed 1 month after commencing DS therapy, and data were validated using an independent external dataset.

RESULTS:

The median overall survival for 145 patients was 18.3 months (95% confidence interval [CI], 15.4‐23.3 months). Only 2 factors were significant on multivariate analysis: a prostate‐specific antigen (PSA) level below the median at the start of DS therapy and a decline >50% in the PSA level after 1 month on DS therapy. Subsequent cutoff point analyses revealed that a PSA level <88 ng/mL at the start of DS therapy and a reduction >53.1% in PSA after the first month of treatment were the most significant factors. These 2 factors were used to construct a prognostic index, which was validated successfully by the external dataset (median overall survival, 18.3 months [95% CI, 16.4‐28.0 months]; concordance, 72% [95% CI, 68%‐76%]). The prognostic index identified 3 prognostic groups: The 2‐year overall survival rate for these 3 groups was 68% (95% CI, 57%‐98%) for the good prognostic group, 40% (95% CI, 31%‐52%) for the intermediate prognostic group, and 12% (95% CI, 5%‐25%) for the poor prognostic group.

CONCLUSIONS:

The easy‐to‐use prognostic index that the authors developed was able to identify a subgroup of patients with CRPC who had prolonged survival only 1 month after starting DS therapy. Cancer 2010. © 2010 American Cancer Society.     

甲醛对雌性大鼠卵巢储备功能的影响

目的：在亚慢性染毒的条件下,研究甲醛对SD雌性大鼠卵巢储备功能的影响。方法：将40只SD雌性大鼠随机分为正常对照组和3个不同浓度（0．2、2．0、20．0mg／kg）的甲醛染毒组。腹腔注射甲醛染毒,每天1次,连续染毒14d,14d后称体质量,并采用股动脉放血处死受试动物,取血清,用化学发光法测定血清雌二醇（E2）浓度;用酶联免疫方法测定抑制素B（inhibin B）浓度;用放射免疫方法测定卵泡刺激素（FSH）和黄体生成激素（LH）的浓度。并解剖摘取卵巢称重,计算脏器系数。结果：甲醛染毒组与对照组比较,各染毒剂量组大鼠血清E2、Inhibin B水平明显降低（P〈0．05）,FSH水平显著升高（P〈0．05）;高、中剂量组大鼠血清LH水平均有所升高,但差异无统计学意义（P〉0．05）。各染毒剂量组卵巢脏器系数显著降低（P〈0．05）。结论：在亚慢性染毒条件下,甲醛对SD雌性大鼠卵巢储备功能有一定损害作用。