The negative impact of the environment on methylation/epigenetic marking in gametes and embryos

A plea for action to protect the fertility of future generations, 17 January 2019

Abstract

Life expectancy has increased since World War II and this may be attributed to several aspects of modern lifestyles. However, now we are faced with a downturn, which seems to be the result of environmental issues. This paradigm is paralleled with a reduction in human fertility: decreased sperm quality and increased premature ovarian failure and diminished ovarian reserve syndromes.

Endocrine Disruptor Compounds (EDCs) and other toxic chemicals: herbicides, pesticides, plasticizers, to mention a few, are a rising concern in today environment. Some of these are commonly used in the domestic setting: cleaning material and cosmetics and they have a known impact on epigenesis and imprinting via perturbation of methylation processes. Pollution from Poly Aromatic Hydrocarbons (PAH), particulate matter (PM), <10 and <2.5 μm and ozone, released into the air all affect fertility. Poor food processing management is a source DNA adducts formation, impairing gametes quality. An important question to be answered is that of nanoparticles (NPs) that are present in food and which are thought to induce oxidative stress. Now is the time to take a step backwards. Global management of the environment and food production is required urgently in order to protect the fertility of future generations.

Reference.

DES and the GENES

Impact of endocrine disrupting chemicals exposure on fecundity as measured by time to pregnancy

A systematic review;, Environmental research, 2018 Dec

Abstract

BACKGROUND
Emerging scientific evidence suggests that exposure to environmental pollutants is associated with negative effects on fecundity as measured by time to pregnancy (TTP).

OBJECTIVES
To conduct a systematic review of the literature on the association between selected endocrine disrupting chemicals (EDCs), and fecundity as measured by TTP in humans. Compounds included in this review are: brominated flame retardants (BFRs) such as hexabromocyclododecane, tetrabromobiphenol A and polybrominated diphenyl ethers; organophosphates flame retardants (OPFRs); and phthalates.

METHODS
Scopus, MEDLINE via Ebscohost and EMBASE databases were searched for articles exploring the relationships between selected EDCs and fecundity as measured by time to pregnancy. We assessed the quality of included studies and evidence for causality was graded using the criteria developed by the World Cancer Research Fund.

RESULTS
14 studies of 191 full-text articles assessed for eligibility were included for qualitative synthesis. Five studies examined BFRs and 10 studies examined phthalates. Among the fourteen, one study assessed both BFRs and phthalates. There were no studies which investigated fecundity as measured by TTP on HBCD, TBBPA, or OPFRs. We recorded plausible fecundity outcomes as measured by TTP related to some of these EDCs. BFRs or phthalates increased TTP. However, results were inconsistent.

CONCLUSION
We recorded mostly weak associations between exposure to selected EDCs and fecundity. However, evidence was considered limited to conclude a causal relationship due to inconsistency of results. The health risks posed by these chemicals in exposed populations are only beginning to be recognized and prospective measurement of the environmental effects of the chemicals in large cohort studies are urgently needed to confirm these relationships and inform policies aimed at exposure prevention

Childhood obesity before 12 years of age appears to increase the risk of female infertility in later life

Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study

2018 Study Abstract

Objective
To evaluate whether childhood obesity is associated with infertility in women’s reproductive-aged life.

Design
Prospective longitudinal study.

Setting
Not applicable.

Intervention(s)
None.

Patient(s)
A total of 1,544 girls, aged 7–15 years in 1985, and who completed questionnaires at follow-up in 2004-2006 and/or 2009-2011.

Main Outcome Measure(s)
Infertility was defined as having difficulty conceiving (had tried for ≥12 months to become pregnant without succeeding) or having seen a doctor because of trouble becoming pregnant.

Result(s)
At ages from 7–11 years, girls at both the lower and upper end of the body mass index (BMI) z score had increased risk of infertility. Compared with normal weight girls, those with obesity at ages 7–11 years were more likely in adulthood to report infertility (adjusted relative risk [aRR] = 2.94, 95% confidence interval [CI] 1.48–5.84), difficulty conceiving (aRR = 3.89, 95% CI 1.95–7.77), or having seen a doctor because of trouble becoming pregnant (aRR = 3.65, 95% CI 1.90–7.02) after adjusting for childhood age, follow-up length, highest parental education, and marital status.

Conclusion(s)
Childhood obesity before 12 years of age appears to increase the risk of female infertility in later life.

Le lien entre la prise de distilbène de la (grand-)mère et la stérilité de la descendance

Toute une histoire, vidéo publiée le 5 octobre 2015

Le distilbene est un “modèle” des perturbateurs endocriniens.

Le Distilbène DES, en savoir plus

Une fille Distilbène sans enfants témoigne

Extrait d’un journal de bord d’une femme numérique, juin 2017

“Il faut de tout pour faire un monde”,
… et …
“à toute chose malheur est bon”.

dit on… voici un témoignage, d’une fille distilbène, qui sort de l’ordinaire…

Le Distilbène DES, en savoir plus

Transgenerational effects of chemotherapy

Both male and female children born to women exposed to chemotherapy have fewer children

2018 Study Highlights

  • Cancer survival rates have been improving.
  • Little is known about the generational effects of chemotherapy-exposure.
  • The children of chemotherapy-exposed women have fewer live births compared to matched controls.
  • Further research needs to validate these findings.

Abstract

Background
There is little known about the transgenerational effect of chemotherapy. For example, chemotherapy is known to decrease fecundity in women. But if women are able to have offspring after chemotherapy exposure, do these children also have decreased fecundity?

Methods
This study is a retrospective cohort study utilizing the Utah Population Database (UPDB), a comprehensive resource that links birth, medical, death and cancer records for individuals in the state of Utah. The male and female children (F1 generation) of chemotherapy-exposed women (F0 generation) were identified. The number of live births (F2 generation) to this F1 generation was compared to two sets of chemotherapy-unexposed, matched controls using conditional Poisson regression models (regression coefficient, 95% confidence interval, P-value). The first unexposed was established using the general population and the second unexposed was established using first cousins to the F1 generation.

Results
The exposed F1 individuals had 77.2% fewer children (−1.48; −2.51 to −0.70; p = 0.001) relative to the unexposed general population. F1 males had 86.9% fewer children (−2.03; −4.91 to −0.51; p = 0.005) and F1 females had 70.5% fewer children (−1.22; −2.40 to −0.36; p = 0.016). When comparing to their unexposed cousins, the F1 generation (both sexes combined) had 74.3% (−1.36; −2.82 to −0.29; p = 0.029) fewer children.

Conclusion
The sons and daughters (F1 generation) of chemotherapy-exposed women have fewer live births when compared to both matched, unexposed general population and cousin controls. Chemotherapy may have a transgenerational effect in exposed women which needs further investigation.

L’effondrement de la spermatogénèse et la manipulation des normes

À la recherche des contrées spermatiques

Publié par Luc Perino, médecin généraliste, humeur du 22/05/2018

Parfois les chiffres s’expriment d’eux-mêmes sans qu’il soit nécessaire de les faire parler. En 1940, la quantité de spermatozoïdes par ml de sperme était de 113 millions. Cinquante ans plus tard, en 1990, elle était de 66 millions. Pendant la même période, le volume de l’éjaculat est passé de 3.40 ml à 2.75 ml.

Alors qu’un degré de réchauffement climatique fait l’objet d’un catastrophisme rabâché sur tous les médias, cet effondrement de la spermatogénèse se déroule dans le plus grand silence. Ce déficit de vulgarisation de la biologie et de la médecine, comparées à toutes les autres sciences dures ou molles, est un problème chronique qui provient essentiellement de la manipulation des normes.

Ainsi, devant cette catastrophe spermatique, l’OMS a tout simplement modifié les normes de l’hypospermie (limite à partir de laquelle on considère le sperme comme insuffisant). Surprenante manipulation. Pour l’éjaculat, cette norme était 3ml en 1940, 2ml en 1999 et 1,5 ml en 2010. Pour le taux de spermatozoïdes par ml, on a vite oublié les 66 millions de 1990, pour tomber rapidement à 20 millions en 1999 et à 15 en 2010 ! On a même décrété que la fertilité pouvait subsister jusqu’à 5 millions, sans considérer qu’un spermatozoïde victorieux qui pénètre un ovule du XXI° siècle a combattu vingt fois moins d’adversaires qu’en 1940.

Nous savons depuis longtemps que les multiples perturbateurs endocriniens de l’agro-alimentaire et de la pétrochimie sont à l’origine de cette dégénérescence spermatique, et nous savons depuis peu que les marques épigénétiques de ce processus sont héritables.

On peut expliquer le silence autour de ces faits de deux façons, l’une réfléchie, l’autre primesautière.

  1. La première résulte d’un lobbysme bien compris pour ménager le système productif qui structure toute notre société.
  2. La seconde est un mélange confus de sentiments inavouables et contradictoires : avec 7 milliards d’habitants, faisons fi des problèmes de fécondité, espérons que l’hypofertilité épargnera notre pays ou notre communauté socio-culturelle, on inventera de nouvelles procréations médicalement assistées, etc. Lorsque l’autruche met sa tête dans le sable, c’est peut-être parce qu’elle a honte.

Les spermatozoïdes deviennent encore plus rares et plus fragiles que les abeilles et le dogme de la croissance du PIB est intouchable. Après avoir sauvé plusieurs industries en abaissant les normes de la spermatogenèse, la docile OMS a également favorisé l’industrie pharmaceutique en abaissant les normes de la glycémie et de la tension artérielle.

Devant l’impossible vulgarisation des sciences biomédicales, il ne nous reste plus qu’à espérer qu’il subsistera des contrées spermatiques où nos filles pourront aller se faire féconder…

En Savoir Plus

Maternal antidepressant use associated with increased risk of miscarriage

Major depression, antidepressant use, and male and female fertility : Cohort study

2018 Study Abstract

Objective
To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments.

Design
Cohort study, DOI: https://doi.org/10.1016/j.fertnstert.2018.01.029, May 2018.

Setting
Clinics.

Patient(s)
Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility).

Intervention(s)
Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD.

Main Outcome Measure(s)
Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS).

Result(s)
Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception.

Conclusion(s)
Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant.

Toxic substances linked to a range of adverse health impacts present in carpets sold in the EU

Swept under the rug: new report reveals toxics in European carpets threatening health, environment and circular economy

A new study identifies over 59 hazardous substances found in carpets sold in the EU, including endocrine disruptors and carcinogens, linked to serious health conditions such as cancers, learning disabilities and fertility problems. Exposure to these toxics via inhalation, ingestion and dermal contact proves extremely harmful to pregnant women, babies and small children who are particularly vulnerable to the effects of exposure to chemicals, as well as workers in the carpet industry who are exposed to those chemicals because of inadequate safety measures. Many of these toxic chemicals are also persistent polluters that stay in the environment and can cause adverse impacts on ecosystems. In some cases, health and environmental impacts only show decades later.

Hazardous toxics in carpets also pose additional obstacles to the recycling process, impacting the quality of the recycled end material and the cost-effectiveness of recycling. Less stringent regulations for recycled materials can lead to now-restricted chemicals persisting in recycled products and consequently harm health. In addition, at least 37 toxic substances have not been restricted and/or banned for use in carpets. Many of these have not even been fully evaluated for their health and environmental impacts. 10 substances are currently identified by the EU as Substances of Very High Concern (SVHC), of which only 4 are banned from the market.

The report contains a series of clear recommendations to the EU, Member States and manufacturers aimed at adopting a health-first approach towards the circular economy. It recommends protecting the environment and the health of European citizens by eliminating toxic substances, strengthening regulations for new products, consistent and faster chemicals regulation as well as producer responsibility and eco-design measures to ensure toxic-free carpets.

Reference.

Phthalate prenatal exposure can affect mens’ fertility and reproductive capacity of several generations

Prenatal exposure to consumer product chemical may affect male fertility in future generations

Chicago, IL – Chemicals found in a variety of routinely used consumer products may be contributing to the substantial drop in sperm counts and sperm quality among men in recent decades, a new study in mice suggests.

The study found the effect of chemicals that disrupt the body’s hormones, called endocrine-disrupting chemicals, may extend beyond more than one generation. The research results was presented Monday, March 19, at ENDO 2018, the 100th annual meeting of the Endocrine Society, in Chicago, Ill.

“Sperm counts among men have dropped substantially over the last few decades, but the reason for such an alarming phenomenon is not known. These results suggest that when a mother is exposed to an endocrine disruptor during pregnancy, her son and the son’s future generations may suffer from decreased fertility or hormone insufficiency,”

said lead author Radwa Barakat, B.V.S.C., M.Sc., of the College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Ill.

The researchers studied the effect of di-(2-ethylhexyl) phthalate (DEHP), which is among the most widely used endocrine-disrupting chemicals. It is found in a wide array of industrial and consumer products, including polyvinyl chloride (PVC) piping and tubing, cosmetics, medical devices and plastic toys. The study found that male mice exposed to DEHP prenatally had significantly less testosterone in their blood and fewer sperm in their semen. Consequently, they lost fertility at an age when they normally would have been fertile.

“Most surprisingly, the male mice born to male mice that were exposed to DEHP also exhibited similar reproductive abnormalities—indicating prenatal exposure to DEHP can affect the fertility and reproductive capacity of more than one generation of offspring,” “Therefore, DEHP may be a contributing factor to the decreased sperm counts and qualities in modern men compared to previous generations.”

Barakat said.

Barakat and colleagues gave pregnant mice one of four doses of DEHP, or a type of corn oil, from 11 days after they conceived until birth.

Adult males born to these mice were bred with unexposed female mice, to produce a second generation of mice. Young adult males from this second generation were bred with unexposed females to produce a third generation. When each generation of mice was 15 months old, the researchers measured sex hormone levels, sperm concentrations and sperm motility, or movement (a potential sign of infertility).

In second-generation males, only those descended from mice in the highest DEHP exposure group had abnormal reproductive results—lower testosterone concentration, sperms levels and sperm motility. Third-generation males descended from DEHP-exposed mice also exhibited reproductive abnormalities at age 15 months, even those descended from mice that received a lower dose of the chemical. The researchers were surprised to find that the lowest DEHP dose group exhibited the greatest abnormalities.

“This study underscores the importance of educating public to try their best effort to reduce their exposure to this chemical and also the need to substitute this chemical with a safer one,”

Barakat said.