Parents’ Preconception Well-Being Affects Child’s Future Health

A series of three articles, published online April 16 in the Lancet, shine a light on this critical period

Medscape Medical News reviewed emerging evidence showing that preconception health of the mother- and father-to-be — especially their diet and weight — affects fertilization, embryo development, and even their child’s risk of future cardiometabolic disease.

Health and nutrition of both men and women before conception is important not only for pregnancy outcomes but also for the lifelong health of their children and even the next generation. The preconception period can be seen in three different ways: from a biological standpoint as the days and weeks before embryo development; from the individual perspective as the time of wanting to conceive; and through a population lens as any time a women is of childbearing age. This Series of three papers highlights the importance and summarises the evidence of preconception health for future health and suggests context-specific interventions. It also calls for a social movement to achieve political engagement for health in this particular phase in life.

Before the beginning : nutrition and lifestyle in the preconception period and its importance for future health

Summary

A woman who is healthy at the time of conception is more likely to have a successful pregnancy and a healthy child. We reviewed published evidence and present new data from low-income, middle-income, and high-income countries on the timing and importance of preconception health for subsequent maternal and child health. We describe the extent to which pregnancy is planned, and whether planning is linked to preconception health behaviours. Observational studies show strong links between health before pregnancy and maternal and child health outcomes, with consequences that can extend across generations, but awareness of these links is not widespread. Poor nutrition and obesity are rife among women of reproductive age, and differences between high-income and low-income countries have become less distinct, with typical diets falling far short of nutritional recommendations in both settings and especially among adolescents. Several studies show that micronutrient supplementation starting in pregnancy can correct important maternal nutrient deficiencies, but effects on child health outcomes are disappointing. Other interventions to improve diet during pregnancy have had little effect on maternal and newborn health outcomes. Comparatively few interventions have been made for preconception diet and lifestyle. Improvements in the measurement of pregnancy planning have quantified the degree of pregnancy planning and suggest that it is more common than previously recognised. Planning for pregnancy is associated with a mixed pattern of health behaviours before conception. We propose novel definitions of the preconception period relating to embryo development and actions at individual or population level. A sharper focus on intervention before conception is needed to improve maternal and child health and reduce the growing burden of non-communicable diseases. Alongside continued efforts to reduce smoking, alcohol consumption, and obesity in the population, we call for heightened awareness of preconception health, particularly regarding diet and nutrition. Importantly, health professionals should be alerted to ways of identifying women who are planning a pregnancy.

Reference

Origins of lifetime health around the time of conception: causes and consequences

Summary

Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.

Reference

Intervention strategies to improve nutrition and health behaviours before conception

Summary

The nutritional status of both women and men before conception has profound implications for the growth, development, and long-term health of their offspring. Evidence of the effectiveness of preconception interventions for improving outcomes for mothers and babies is scarce. However, given the large potential health return, and relatively low costs and risk of harm, research into potential interventions is warranted. We identified three promising strategies for intervention that are likely to be scalable and have positive effects on a range of health outcomes: supplementation and fortification; cash transfers and incentives; and behaviour change interventions. On the basis of these strategies, we suggest a model specifying pathways to effect. Pathways are incorporated into a life-course framework using individual motivation and receptiveness at different preconception action phases, to guide design and targeting of preconception interventions. Interventions for individuals not planning immediate pregnancy take advantage of settings and implementation platforms outside the maternal and child health arena, since this group is unlikely to be engaged with maternal health services. Interventions to improve women’s nutritional status and health behaviours at all preconception action phases should consider social and environmental determinants, to avoid exacerbating health and gender inequalities, and be underpinned by a social movement that touches the whole population. We propose a dual strategy that targets specific groups actively planning a pregnancy, while improving the health of the population more broadly. Modern marketing techniques could be used to promote a social movement based on an emotional and symbolic connection between improved preconception maternal health and nutrition, and offspring health. We suggest that speedy and scalable benefits to public health might be achieved through strategic engagement with the private sector. Political theory supports the development of an advocacy coalition of groups interested in preconception health, to harness the political will and leadership necessary to turn high-level policy into effective coordinated action.

Reference

Chemicals in lavender and tea tree oil appear to be hormone disruptors

More evidence essential oils ‘make male breasts develop’

Chicago, IL – A new study lends further evidence to a suspected link between abnormal breast growth in young boys—called prepubertal gynecomastia—and regular exposure to lavender or tea tree oil, by finding that key chemicals in these common plant-derived oils act as endocrine-disrupting chemicals. The study results was at ENDO 2018, the Endocrine Society’s 100th annual meeting in Chicago.

Lavender and tea tree oil are among the so-called essential oils that have become popular in the United States as alternatives for medical treatment, personal hygiene and cleaning products, and aromatherapy. Various consumer products contain lavender and tea tree oil, including some soaps, lotions, shampoos, hair-styling products, cologne and laundry detergents.

“Our society deems essential oils as safe,” “However, they possess a diverse amount of chemicals and should be used with caution because some of these chemicals are potential endocrine disruptors.”

said study lead investigator J. Tyler Ramsey, a postbaccalaureate research fellow at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

An endocrine-disrupting chemical is a chemical in the environment that interferes with hormones and their actions in the body.

Lavender oil and tea tree oil pose potential environmental health concerns and should be investigated further

Male gynecomastia occurring before puberty is relatively rare, but a growing amount of cases have been reported to coincide with topical exposure to lavender and tea tree oil, and the condition went away after the boys stopped using the oil-containing products, Ramsey said. Researchers at the NIEHS, including Kenneth Korach, Ph.D., a co-investigator for the new study, previously found laboratory evidence that lavender and tea tree oil have estrogenic (estrogen-like) properties and anti-androgenic (testosterone inhibiting-like) activities, meaning they compete or hinder the hormones that control male characteristics, which could affect puberty and growth.

Under Korach’s direction, Ramsey and his NIEHS colleagues went a step further. From the hundreds of chemicals that comprise lavender and tea tree oil, they selected for analysis eight components that are common and mandated for inclusion in the oils. Four of the tested chemicals appear in both oils: eucalyptol, 4-terpineol, dipentene/limonene and alpha-terpineol. The others were in either oil: linalyl acetate, linalool, alpha-terpinene and gamma-terpinene. Using in vitro, or test tube, experiments, the researchers applied these chemicals to human cancer cells to measure changes of estrogen receptor- and androgen receptor-target genes and transcriptional activity.

All eight chemicals demonstrated varying estrogenic and/or anti-androgenic properties, with some showing high or little to no activity, the investigators reported. Ramsey said these changes were consistent with endogenous, or bodily, hormonal conditions that stimulate gynecomastia in prepubescent boys.

Of further concern, according to Ramsey, is that many of the chemicals they tested appear in at least 65 other essential oils. Essential oils are available without a prescription and are not regulated by the U.S. Food and Drug Administration. Thus, the public should be aware of these findings and consider all evidence before deciding to use essential oils. The NIEHS Division of Intramural Research funded this study through its support of Korach.

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.

What has gender got to do with chemicals ?

How POPs, hazardous chemicals and waste have different exposures and impacts on women’s and men’s health

    • How are women and men differently impacted in their health by POPs / hazardous chemicals & waste?
    • How do women and men’s occupations and roles at home and at work influence exposure to POPs / hazardous chemicals & waste?
    • What best practices with women and men’s leadership exist to substitute and eliminate POPs / hazardous chemicals & waste exist?

In Africa’s most populated country, Nigeria, with its almost 200 million inhabitants, toxic pollution from waste is yet another challenge to society, economy and security.

Filmmaker Laure Poinsot, shows how women and men are impacted by toxic pollution from waste and chemicals – partly imported illegally from Europe and America – while it visits the hidden e-waste markets and waste dumps around the country.

The film produced by the BRS Conventions , WECF and WEP, also shows how social entrepreneurs, women’s organisations, authorities and the UN are working on solutions, such as waste collection, recycling and production of safe pesticides from the indigenous NEEM tree.

More Information

    • Gender Dimensions of Hazardous Chemicals and Waste policies under the Basel, Rotterdam and Stockholm Conventions, wecf.eu, 2017/11-November.
    • WECF International press release, 15th of January 2018.

Cumulative effects of phthalates harm Leydig cells during fetal development

More bad news for sperm…

2018 Study Highlights

  • Phthalates dose-dependently cause fetal Leydig cell aggregation.
  • DEHP is more potent to inhibit testosterone production than DEP.
  • DEP and DEHP can elicit dose addition effect on FLC development

Abstract

Phthalate diesters, including di-(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP), are chemicals to which humans are ubiquitously exposed. Humans are exposed simultaneously to multiple environmental chemicals, including DEHP and DEP. There is little information available about how each chemical may interact to each other if they were exposed at same time. The present study investigated effects of the combinational exposure of rats to DEP and DEHP on fetal Leydig cell development. The results showed that the gestational (GD12-20) exposure of DEP + DEHP resulted in synergistic and/or dose-additive effects on the development of fetal Leydig cell. The lowest observed adverse-effect levels (LOAEL) for fetal Leydig cell (aggregation and cell size), and StAR expressions were of 10 mg/kg and, lower than when these chemicals were exposed alone. Also, mathematical modeling the response curves supports the dose-addition model over integrated-addition model. Overall, these data demonstrate that individual phthalate with a similar mechanism of action can elicit cumulative, dose additive, and sometimes synergistic, effects on the development of male reproductive system when administered as a mixture.

Sources
  • In utero combined di-(2-ethylhexyl) phthalate and diethyl phthalate exposure cumulatively impairs rat fetal Leydig cell development, Science Direct, Volume 395, Pages 23–33, 15 February 2018.
  • Very high magnification micrograph of Leydig cells feature image wiki.

EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

BACKGROUND
Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

OBJECTIVES
Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

METHODS
We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

RESULTS
We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

CONCLUSIONS
Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.

Discussion

Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Do we need to choose between improved sperm selection or efficacy ?

The latest attempt to improve the sperm’s path

Our goal in the in vitro fertilization laboratory is to maximize the ratio between the number of oocytes retrieved and the production of highly viable embryos. We receive the raw material from our patients (oocytes and sperm cells) and, with our knowledge and the available technologies; we try to improve our success rates day by day. One of our endpoints should be the objective application of validated, repeatable, and non-biased therapies and technologies. Few options remain available for oocytes as all the oocytes will be treated to achieve fertilization. In the case of sperm, millions of cells are available to us, but only a few of them will be used. Is there room to improve the sperm’s path? We must move away from the classical methods of sperm selection (swim up or gradients) and pursue any kind of technology that may take into consideration their molecular characteristics, which are related to successful fertilization, embryo development, and live birth.”…

…continue reading What else can we do? The latest attempt to improve the sperm’s path on Fertility and Sterility, Volume 108, Issue 3, Pages 444–445, September 2017.

Multiple generations of chemical exposure may lead to absolute infertility in males

Science : Are we in a male fertility death spiral ?

Written by Pete Myers, Environmental Health Sciences, July 26, 2017.

Margaret Atwood’s 1985 book, The Handmaid’s Tale, played out in a world with declining human births because pollution and sexually transmitted disease were causing sterility.

Does fiction anticipate reality? Two new research papers add scientific weight to the possibility that pollution, especially endocrine disrupting chemicals (EDCs), are undermining male fertility.

“The study is a wakeup that we are in a death spiral of infertility in men”

Frederick vom Saal, Curators’ Distinguished Professor Emeritus of Biological Sciences at the University of Missouri and expert on endocrine disruption.

The first, published Tuesday, is the strongest confirmation yet obtained that human sperm concentration and count are in a long-term decline: more than 50 percent from 1973 to 2013, with no sign that the decline is slowing.

“The study provides a mechanistic explanation for a progressive decrease in sperm count over generations.”

Frederick vom Saal.

The second, published last week by different authors, offers a possible explanation. It found that early life exposure of male mouse pups to a model environmental estrogen, ethinyl estradiol, causes mistakes in development in the reproductive tract that will lead to lower sperm counts.

But there is much more to this study, led by Washington State University doctoral student Tegan Horan and published in the journal PLoS Genet. The senior author on the paper, Washington State University’s Distinguished Professor of Molecular Biosciences, Patricia Hunt, is one of the world’s leading authorities on how endocrine disrupting chemicals harm the development of sperm and eggs.

What makes this study unique is that it examined what happened when three successive generations of males were exposed—instead of just looking only at the first. Hunt, in an email, said

“we asked a simple question with real-world relevance that had simply never been addressed.”

Successive, constant exposure

More than a dozen papers have now been published on “trans-generational epigenetic inheritance,” where exposure in a great-grandmother causes adverse effects in great-grandson—without further exposures and without changes in DNA sequence.

But crucially these experiments typically only expose one generation—the first—rather induce ongoing exposures across generations, which is the reality of human experience.

In the real world, since World War II, successive generations of people have been exposed to a growing number and quantity of environmental estrogens—chemicals that behave like the human hormone estrogen. Thousands of papers published in the scientific literature (reviewed here) tie these to a wide array of adverse consequences, including infertility and sperm count decline.

This phenomenon—exposure of multiple generations of mammals to endocrine disrupting compounds—had never been studied experimentally, even though that’s how humans have experienced EDC exposures for at least the last 70 years. That’s almost three generations of human males. Men moving into the age of fatherhood are ground zero for this serial exposure.

So Horan, Hunt and their colleagues at WSU set out to mimic, for the first time, this real-world reality. They discovered that the effects are amplified in successive generations.

They observed adverse effects starting in the first generation of mouse lineages where each generation was exposed for a brief period shortly after birth. The impacts worsened in the second generation compared to the first, and by the third generation the scientists were finding animals that could not produce sperm at all. This latter condition was not seen in the first two generations exposed. Details of the experimental results actually suggested that multiple generations of exposure may have increased male sensitivity to the chemical.

Laura Vandenberg, an expert on endocrine disruption effects at the University of Massachusetts, Amherst and who did not participate in either study called Horan and Hunt’s work

“an elegantly designed study that looks at several really important issues in environmental health.” “As the authors rightly point out, over the past several decades, exposures to environmental chemicals—and estrogens in particular—have continued to rise.” Exposure today, is life-long, not episodic. “Remarkably, the damage that is seen in any one generation gets worse and worse as more generations are exposed,” “I have never seen a study examine these different generations so beautifully – this is a tremendous amount of work!”

Vandenberg said.

Long-term decline

The first paper, published Tuesday in the journal Human Reproduction, analyzes data from all studies on the topic researchers could find published in the scientific literature between 1981 and 2013.  Researchers, including Hagai Levine of the Hebrew University of Jerusalem and Shanna Swan of the Icahn School of Medicine in New York found 185 studies that sampled a total of 42,000 men across four  decades beginning in 1973.

“20 percent of Danish men do not father children.”

Niels Skakkebæk, University of Copenhagen

Declines in sperm concentration and total sperm count were “highly significant” for samples from North America, Europe, Australia and New Zealand. Those from South America, Asia and Africa were not significant, possibly a result of a much smaller sample size.

Hunt sees considerable linkage between the two studies.

“Our data are showing that things get progressively worse as subsequent generations are exposed,” “These large changes in human sperm count and concentration reveal that we are already well down the road.”

she said.

Niels Skakkebæk, a Danish pediatrician and researcher whose 1992 paper with Elisabeth Carlsen reporting large long-term declines in human sperm count kicked off over 20 years of debate, added:

“These two new papers add significantly to existing literature on adverse trends in male reproductive health problems. Importantly, the data are in line with data on testicular cancer which is increasing worldwide.” “Here in Denmark, there is an epidemic of infertility,” “More than 20 percent of Danish men do not father children.” “Most worryingly [in Denmark] is that semen quality is in general so poor that an average young Danish man has much fewer sperm than men had a couple of generations ago, and more than 90 percent of their sperm are abnormal.”

Skakkebæk did not participate in either study.

Skakkebæk’s concerns about younger men are reinforced by some of the details of the new sperm study because it reports that men in a subgroup of the total sample whose partners are not yet pregnant nor do they have children (i.e., they are not confirmed fertile men) have experienced a drop in average sperm count of almost 50 percent over four decades, to 47 million sperm per milliliter. That puts counts close to what the World Health Organization considers impairment in ability fertilize an egg—40 million sperm per milliliter.

Indicator of male health?

Poor sperm count is associated with overall morbidity and mortality.

That’s the average reduction. Every average has a distribution: Some with more reduction, some less. And those who fall in the “more” category may wind up below the level where WHO considers fertilization unlikely—15 million sperm per milliliter. The new study specifically notes that a high proportion of men from Western countries have concentrations below 40 million per milliliter.

The sperm count study raises a larger issue, beyond reductions in the ability to fertilize an egg.

“Poor sperm count is associated with overall morbidity and mortality,” “A decline in sperm count might be considered as a ‘canary in the coal mine’ for male health across the lifespan. Our report of a continuing and robust decline should, therefore, trigger research into its causes, aiming for prevention.”

the authors wrote.

Are we, as suggested by Dr. vom Saal, in a “death spiral” of male infertility? And if so, what are the larger implications? Perhaps the most far-reaching, if this is true, would be what this means there will be changes in age distributions in populations in nations suffering from this spiral.

A core assumption driving economic policies around the world is that growth is essential. Populations that are declining because of infertility face big problems because economic activity depends upon have a large number of working people compared to those that are retired. Expectations for economic growth diminish.

Would further declines in male fertility undermine the assumptions that fuel faith in economic growth, as the age distribution shifts to one with more retired people and fewer working? These are vital questions that traditional demographers have largely chosen to ignore.

Pete Myers,
Founder and chief science officer of Environmental Health News, publisher of EHN.org and DailyClimate.org.

Featured image credit womenshealth.gov.

Sperm concentration has declined more than 50% in less than 40 years

Temporal trends in sperm count : a systematic review and meta-regression analysis

New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years and points toward importance of further investigation into environmental factors.

Temporal trends in sperm count: a systematic review and meta-regression analysis, by the Hebrew University of Jerusalem, points to an alarming decline in male reproductive health, and suggests worrying implications for male fertility and reproduction. Based on data collected on men from North America, Europe, Australia and New Zealand from 1973 to 2011, the study performed the first ever systematic review and meta-analysis on sperm counts and found a decline of more than 59%, with no sign of levelling off over time. The findings are significant considering that low sperm levels have also been linked with higher risks of hospitalization and death.

2017 Study Abstract

BACKGROUND
Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality.

OBJECTIVE AND RATIONALE
To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group.

SEARCH METHODS
PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981–2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973–2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group (‘Unselected by fertility’ versus ‘Fertile’), geographic group (‘Western’, including North America, Europe Australia and New Zealand versus ‘Other’, including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models.

OUTCOMES
SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models −0.70 million/ml/year; 95% CI: −0.72 to −0.69; P < 0.001; slope in adjusted meta-regression models = −0.64; −1.06 to −0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (−1.38; −2.02 to −0.74; P < 0.001) and among Fertile Western (−0.68; −1.31 to −0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (−5.33 million/year, −7.56 to −3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (−2.06 million/ml, −3.38 to −0.74; P = 0.004 and −8.12 million, −13.73 to −2.51, P = 0.006, respectively).

WIDER IMPLICATIONS
This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50–60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Sources and Press Releases
  • Temporal trends in sperm count: a systematic review and meta-regression analysis, Hum Reprod Update, doi.org/10.1093/humupd/dmx022, 25 July 2017.
  • New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years, Health & Environment, 26 July 2017.
  • Featured image credit freemalaysiatoday.

Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring

DES is one of the major disasters in medicine and it is mandatory to tackle and promote programs of DES-related cancer prevention

2017 Study Highlights

  • Diethylstilbestrol (DES) is a synthetic, non-steroidal estrogen of the stilbestrol group acting as an endocrine disruptor.
  • Adverse pregnancy outcomes, infertility, cancer, and early menopause have been identified in women exposed to DES, their offspring, and subsequent generations.

Abstract

Diethylstilbestrol (DES) was an orally active estrogen prescribed to the pregnant women to prevent miscarriages.

DES is known as a ‘biological time bomb’ and long-term effects of DES have been recorded in the mothers exposed to DES and their offspring (DES-daughters and DES-sons). Adverse pregnancy outcomes, infertility, cancer, and early menopause have been discovered in women exposed to DES, and some events occur in their offspring and subsequent generations. An increased risk of breast cancer is not limited to the DES-exposed daughters.

There is an urgent need to find ways to stop the inheritance cycle of DES and prevent adverse effects of DES in the future generations. The present article reviews the health implications of DES exposure and screening exams currently recommended to DES daughters and their offspring.

  • Reproductive toxicology (Elmsford, N.Y.)., Volume 71, August 2017, Pages 71–77, 2017 Apr 28. Image credit jason wilson.
DES DiEthylStilbestrol Resources