Prostate cancer is the most common cancer in men in the EU representing 25% of all male new cancer cases diagnosed. 1 in 7 men in UK will develop this condition during his
lifetime. All European countries (except those with high incidence already) have seen dramatically increasing incidence trends in recent years.
All EU countries are experiencing strong rises in testicular cancer. Incidence has doubled over the past 25 years. Cancer of the testes is now the most common cancer of young men, peaking at 25-30 years.
An association between in utero exposure to DES and abnormalities of men’s urogenital systems was also found. The most common abnormalities are epididymal cysts, undescended testes, and small testes. A recent study suggested an increased incidence of testicular cancer among men exposed in utero to DES.
When early reports of increased frequency of uterine and ovarian adenocarcinoma in offspring of mice exposed in utero to DES were first published in the mid-1980s, they raised concern regarding possible adverse effects on the third generation of humans exposed to DES.
A study of 28 daughters (mean age 20 years) of women exposed to DES in utero showed that these third-generation women had no abnormalities of the genital tract, and no cases of endometrial, ovarian, cervical, or vaginal carcinoma, or intraepithelial neoplasia of the cervix or vagina were detected. Review of their mothers’ records indicated that 61.5% of the mothers exposed to DES in utero had structural changes of the cervix, upper vagina, or vaginal epithelium. The main limitations of this study were the small sample size and the age of the women, who might have been too young to reflect the true rate of subsequent genital malignancies.
The absence of abnormalities of the lower genital tract in third-generation women compared with the high frequency of these abnormalities in their mothers suggests that third-generation carry-over effects of DES exposure are rare.
A recent case report of an ovarian malignancy in a third-generation adolescent raised the possibility of an association between her malignancy and her grandmother’s use of DES. The authors described a 15-year-old girl with small cell carcinoma of the ovary whose maternal grandmother had been taking DES while she was pregnant with the patient’s mother. Although this is an anecdotal case, the rarity of this disorder suggests that DES exposure could have a trans-generational effect.
An increased rate of hypospadias has recently been reported in third-generation men. A Dutch cohort study compared 205 sons of women who were exposed to DES in utero with 8934 men with no such history. Four (2%) of the exposed sons had hypospadias, compared with nine (0.01%) in the control group.
Differences between human and mice models in the effects of DES on the third generation suggest that the effect observed in mice is much greater than in humans. Nevertheless, some authors recommend that third-generation women should be examined carefully for presence of DES-associated changes.
A variety of theories have been proposed for the mechanism of action of multi-generational effects of DES. In mice, the carcinogenicity of DES can apparently be transmitted from prenatally exposed offspring to the next generation. Germ cell mutation has been implicated as the mode of transmission of the genotoxic effect. Imprinting might be another mode of transmission.
Pregnant “DES daughters” and their offspring, NCBI, PMCID: PMC1472948, Can Fam Physician. Apr 10, 2005; 51(4): 493–494.
Autism risk is higher near pesticide-treated fields
Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study
Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.
To evaluate whether residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) Study.
The CHARGE study is a population-based case-control study of ASD, developmental delay (DD), and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25km, 1.5km, and 1.75km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).
Approximately one-third of CHARGE Study mothers lived, during pregnancy, within 1.5 km (just under one mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for 3rd trimester exposures [OR = 2.0, 95% confidence interval (CI) = (1.1, 3.6)], and 2nd trimester chlorpyrifos applications: OR = 3.3 [95% CI = (1.5, 7.4)]. Children of mothers residing near pyrethroid insecticide applications just prior to conception or during 3rd trimester were at greater risk for both ASD and DD, with OR’s ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.
This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, and particularly, organophosphates and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates. Children of mothers who live near agricultural areas, or who are otherwise exposed to organophosphate, pyrethroid, or carbamate pesticides during gestation may be at increased risk for neurodevelopmental disorders.
Further research on gene-by-environment interactions may reveal vulnerable sub-populations.
Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study, Environ Health Perspect; DOI:10.1289/ehp.1307044, 23 June 2014 – PDF
Supplemental Material, Aerial image showing further descriptions of the study population and exposure model, ehp.1307044.s001.
Autism risk higher near pesticide-treated fields, study says, Environmental Health News, autism-and-pesticides, June 23, 2014
Women who take antidepressants during pregnancy may be unknowingly predisposing their infants to type 2 diabetes and obesity later in life
Maternal use of a class of antidepressants called selective serotonin reuptake inhibitors, or SSRIs, resulted in increased fat accumulation and inflammation in the liver of the adult offspring, researchers have demonstrated for the first time in an animal model. This raises new concerns about the long-term metabolic complications in children born to women who take SSRI antidepressants during pregnancy.
Read Antidepressant use during pregnancy may lead to childhood obesity, diabetes, McMaster University, ScienceDaily, 140621213019, June 21, 2014
DES usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced
Previous studies have shown that a carcinogenic effect can be transmitted from female mice exposed prenatally to diethylstilboestrol (DES) to their female offspring. Furthermore, male mice exposed pre-natally to DES can transmit a carcinogenic effect to their offspring through their germ cells.
To study how multi-generational carcinogenesis is transmitted through females exposed pre-natally to DES, the technique of blastocyst transfer was utilized. Blastocysts from strain CD-1 mice exposed pre-natally to vehicle were transferred to mice exposed pre-natally to DES. Among 143 offspring from these transfers, there were 10 ovarian adenomas and 10 uterine adenocarcinomas. Among 92 offspring from blastocyst transfers between mice exposed pre-natally to vehicle only, there was 1 ovarian adenoma and 1 uterine adenocarcinoma. Thus the pre-natal exposure of the host to DES produced a maternal environment which increased the incidence of ovarian and uterine tumors.
The reverse type of transfer was also performed, in which blastocysts from female mice exposed pre-natally to DES were transferred into mice exposed to vehicle only pre-natally. Among 99 offspring derived from DES-exposed germ cells, 6 developed ovarian adenomas and 16 developed uterine adenocarcinomas.
Thus DES also has a multi-generational effect transmitted through the blastocyst, which is consistent with fetal germ cell mutation from DES.
Multi-generational carcinogenesis from diethylstilbestrol investigated by blastocyst transfers in mice, NCBI, PMID: 7705955, Int J Cancer. 1995 Apr 10;61(2):249-52.