Tiny air pollution particles may lead to reduced sperm production

Particulate air pollution linked with reduced sperm production in mice, 2019

New Orleans, LA – Exposure to tiny air pollution particles may lead to reduced sperm production, suggests new research in mice, presented Monday, March 25 at ENDO 2019, the Endocrine Society’s annual meeting.

“Infertility rates are increasing around the world, and air pollution may be one of the main factors,”

said lead researcher Elaine Maria Frade Costa, M.D., Ph.D., of Sao Paulo University in Sao Paulo, Brazil.

The World Health Organization (WHO) estimates that approximately 15 percent of the global population has difficulty with fertility, and male infertility accounts for about half of those problems.

The study looked at the effect of particulate matter (PM) on sperm production. PM is a mixture of solid particles and liquid droplets found in the air. PM2.5 is a fine inhalable particle with diameters that are 2.5 micrometers or smaller. The average human hair is about 70 micrometers in diameters, making it 30 times larger than the biggest fine particle. PM2.5 is known to disrupt the endocrine system in humans and animals. The endocrine system is involved in reproduction, including the production of sperm.

The study included four groups of mice. One was exposed to PM2.5 from Sao Paolo before and after birth, from the day they were weaned from their mother’s milk until adulthood. The second group was exposed only during gestation. The third group was exposed after birth from weaning until adulthood; and the fourth group was exposed only to filtered air during gestation and from the time they were weaned until adulthood.

The researchers analyzed the testes of the mice and their production of sperm. DNA tests were used to evaluate gene expression, the process by which genes in DNA provide instructions for proteins.

The tubes in the testes that produce sperm of all the exposed mice showed signs of deterioration. In comparison with the mice not exposed to PM2.5, the sperm of the first group, which was exposed before and after birth, was of significantly worse quality.

The exposure to PM2.5 led to changes in the levels of genes related to testicular cell function. Exposure to PM2.5 after birth seemed to be the most harmful to testicular function, the study found.

Costa said these changes are epigenetic, which means they are not caused by changes in the DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins a gene expresses.

The research demonstrates for the first time that exposure to air pollution of a large city impairs production of sperm through epigenetics, mainly in exposure after birth, Costa said.

“These findings provide more evidence that governments need to implement public policies to control air pollution in big cities,”

she said. Reference. Featured image.

Endocrine disruptors alter pubertal timing

Endocrine disrupters and possible contribution to pubertal changes

Puberty represents a crucial milestone in one’s reproductive life. For this reason, any effect of the environment on pubertal timing might announce later consequences on reproduction. For the last 20 years, data has accumulated suggesting changes in pubertal timing and a possible role for exposure to endocrine disrupting chemicals (EDCs). This review will summarize the recent data regarding secular trends in age at puberty in boys and girls as well as the likely increase in central precocious puberty incidence in girls. Finally, we will review the epidemiological and animal data suggesting a role for endocrine disrupting chemicals in the reported changes in pubertal timing.

Abstract

The onset of puberty strongly depends on organizational processes taking place during the fetal and early postnatal life. Therefore, exposure to environmental pollutants such as Endocrine disrupting chemicals (EDCs) during critical periods of development can result in delayed/advanced puberty and long-term reproductive consequences. Human evidence of altered pubertal timing after exposure to endocrine disrupting chemicals is equivocal. However, the age distribution of pubertal signs points to a skewed distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon and suggests environmental influences including the possible role of nutrition, stress and endocrine disruptors. Rodent and ovine studies indicate a role of fetal and neonatal exposure to EDCs, along the concept of early origin of health and disease. Such effects involve neuroendocrine mechanisms at the level of the hypothalamus where homeostasis of reproduction is programmed and regulated but also peripheral effects at the level of the gonads or the mammary gland.

Endocrine disruptors alter female reproduction throughout multiple generations

OR23-1 Transgenerational Effects of Endocrine Disrupting Chemicals on Pubertal Timing through Epigenetic Reprogramming of the Hypothalamus

According to a recent animal study, endocrine disruptors, hormone-altering chemicals that are widespread in our environment, can shape the brain through four generations, altering offspring’s maternal behavior, sexual development and reproduction, The Endocrine Society reports.

Abstract

Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquitous presence as complex mixtures affecting development throughout generations. Our goal was to study the effect of a mixture of EDCs on female sexual development during 3 generations. Female rats (F0 generation) were orally exposed to a mixture of 14 anti-androgenic and estrogenic EDCs or corn oil for 2 weeks before and throughout gestation and until weaning. The mixture was composed of plasticizers (BPA, DBP, DEHP), fungicides/pesticides (Vinclozolin, Procymidon, Prochloraz, Epoxynazole, Linurone, p-p’-DDT), UV filters (4-MBC, OMC), Butyl Paraben and the analgesic Acetaminophen. The doses were in the micrograms/kg range in order to represent human exposure. Sexual development (vaginal opening, GnRH interpulse interval and estrous cyclicity) as well as maternal behavior were studied from F1 to F3 generations. At PND21 the mediobasal hypothalamus of the F1 and F3 were removed for gene expression analysis by RNAseq and RT-qPCR as well as for Chromatin Immunoprecipitation of histone modifications at regulatory regions of target genes. While F2 and F3 females showed delayed vaginal opening, decreased percentage of regular estrous cycles and decreased GnRH interpulse interval, no such changes were detected in F1 animals. These reproductive phenotypes were associated with alterations in both transcriptional and histone posttranslational modifications of hypothalamic genes involved in reproductive competence and behavior like kisspeptin (Kiss1), oxytocin (Oxt), estrogen (Esr1), glutamate (Grin2d), dopamine signaling (Th and Drd1) as well as glucocorticoid activity (Nr3c1 and Crh). Concomitant with a decrease in transcriptional activity, we have observed either a decrease of active histone marks (H3K4me3, H3K9ac) for Esr1 and Oxt promoter regions, an increase of repressive histone modifications (H3K27me3, H3K9me3) for Grin2D, Th and Nr3c1 promoter regions or both for the Kiss1 promoter. Up-regulated genes (Pomc, and CRH) showed decreased H3K9me3 and increased H3K9ac at their 5’regulatory regions. F1 females that were exposed in utero to the EDC mixture, showed a reduction in Th mRNA expression and decreased grooming/licking behavior while spending more time resting alone. These alterations on maternal behavior are known to cause transgenerational alterations of the development of the corticotropic and gonadotropic axis. Overall, our data shows that gestational and lactational exposure to an environmentally relevant EDC mixture transgenerationally affects sexual development throughout epigenetic reprogramming of the hypothalamus. Such effects could be mediated by alterations of maternal behavior caused by exposure of the first generation to the EDC mixture.

About DES and the GENES

T-shaped uterus and subtle uterine variances

A need for reliable criteria, Fertility and Sterility, August 2019

Abstract

The ASRM Class VII, the ESHRE/ESGE Class U1, and the T-shaped uterus have a uniquely interesting history. The T-shaped uterus was first described as a diethylstilbestrol– (DES-) related congenital uterine anomaly based on findings from hysterosalpingography by Kaufman in 1977. Together with two similar morphologic forms of the uterus—constricting bands in the uterine cavity and a widening of the lower two-thirds of the uterus—this was included as a separate class of DES-related anomalies by the Buttram and Gibbons 1979 classification, and its further modification—the American Fertility Society classification.

In 2013, ESHRE/ESGE singled out a subtle uterine variance with a thickened lateral wall and a T-shaped uterus. As a result, the diagnosis of subtle uterine variances has increased with the designation of a T-shaped uterus or dysmorphic uterus and surgical repair is offered to enhance fertility. However, there is insufficient evidence to offer it in daily practice even in women with recurrent pregnancy loss, where historically metroplasty of the T-shaped uterus is rarely reported and its surgical correction is always questionable.

In this issue Alonso Pacheco et al. present a nicely done video using three-dimensional ultrasound and hysteroscopy in three cases of what they believe is a T-shaped uterus that is representative in distinguishing three of its subclasses. The authors used three-dimensional ultrasound and hysteroscopy to suggest that T-shaped uterus can be subclassified as T-shaped, Y-shaped, or I-shaped uterus. However, the division still remains arbitrary based on subjective impression of the presence of thickened wall and letter-shaped uterine cavities in these conditions. Discussion.

Evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing

Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study

2019 Study Abstract

Objective
To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls.

Design
Population-based cohort study.

Setting
Not applicable.

Patient(s)
Overall, 15,800 children (70%) born during 2000–2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty.

Intervention(s)
None.

Main Outcome Measure(s)
Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index.

Result(s)

  • In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, −3.8; 95% confidence interval [CI] −6.5, −1.0) and first ejaculation (months, −2.9; 95% CI −5.9, 0.1) and a mean difference of −1.4 months (95% CI −3.3, 0.4) for overall pubertal timing.
  • Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, −1.9; 95% CI −4.0, 0.3) and Tanner breast stages and had a mean difference of −0.9 months (95% CI −2.7, 1.0) for overall pubertal timing.
  • Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role.

Conclusion(s)
This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

Impact of male factor infertility on offspring health and development

Long-term health and developmental outcomes in children conceived with intracytoplasmic sperm injection

2019 Study Abstract

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails.

Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately.

In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently.

Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size.

Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls.

Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions.

The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan.

With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.

Reference. Image credit fertilitysmarts.

Adult and Prenatal Chemical Exposures

Breast Cancer Prevention Partners, with Tracey Woodruff, Ph.D., Mar 2019

  • How am I exposed to chemicals?
  • What are prenatal exposures?
  • How can I reduce my own personal exposures?
  • What more can I do to help make a change?

Featuring BCPP Science Advisory Panel member Tracey Woodruff, Ph.D., Director of the Program on Reproductive Health and the Environment, University of California, San Francisco, Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences and Philip R. Lee Institute for Health Policy Studies at UCSF

Why are ObGyns Talking Toxins ?

Let’s make environmental health part of health care

Doctors from 125 countries want policies to prevent exposure to toxic chemicals

Produced for PRHE by Susan Lamontagne, Public Interest Media Group, for the International Federation of Gynecology and Obstetrics (FIGO) XXI World Congress on September 30, 2015.

Why are Doctors Talking Toxins ?

And how to reduce exposure to toxic chemicals worldwide ?

It’s time to shift the burden of proof, from scientists, back to the chemical industry

Video published on 5 June 2019, by UCSF Program on Reproductive Health and the Environment.

Endocrine disruptors have an impact on reproduction for several generations

Endocrine disruptors transgenerationally alters pubertal timing through epigenetic reprogramming of the hypothalamus

2019 Study Abstract

Endocrine disruptors are a rising concern for public health due to their ubiquitous presence affecting reproductive development throughout generations.

We aim at studying the transgenerational effect of an EDC mixture on female sexual development and reproduction.

Female rats (F0 generation) were orally exposed to a mixture of 14 anti-androgenic and estrogenic EDCs or corn oil for 2 weeks before and throughout gestation and until weaning. The mixture was composed of plasticizers (BPA, DBP, DEHP), fungicides/pesticides (Vinclozolin, Procymidon, Prochloraz, Epoxynazole, Linurone, p-p’-DDT), UV filters (4-MBC, OMC), Butylparaben and the analgesic Acetaminophen. Doses were in the human exposure range (μg/kg).

Sexual development and reproductive parameters (vaginal opening, GnRH secretion, estrous cyclicity and folliculogenesis) were studied from F1 to F3 generations. Maternal behavior was measured from F0 to F2 generations. At PND21, mediobasal hypothalamus of the F1 and F3 were removed for gene expression analysis (RNAseq, RT-PCR) as well as for Chromatin Immunoprecipitation of histone modifications at regulatory regions of target genes.

The results show multiple multi- and transgenerational effects after ancestral EDC exposure. While F2 and F3 females showed delayed vaginal opening, decreased percentage of regular estrous cycles, decreased GnRH interpulse interval and altered folliculogenesis, no such changes were detected in F1 animals. These alterations were accompanied with transcriptional and histone posttranslational modifications of key hypothalamic genes involved in puberty and reproduction. We observed a downregulation of estrogen signaling (Esr1), genes involved in the GnRH network (Kisspeptin, Grin2d, Tac3R), maternal behavior (Th, Oxt, Avp, Drd1, Drd2) and stress responsiveness (Nr3c1). Upregulated gens involved glucocorticoid activity (Crh) and metabolism (Pomc, Cart). Concomitantly with transcriptional levels, while downregulated genes present higher levels of repressive histone marks (H3K9me3, H3K27me3) and decreased levels of activational histone marks (H3K4me3, H3K9ac), upregulated genes present the opposite pattern. Such histone marks related to changes in the polycomb/thritorax group of protein balance, involved in the control of female puberty. F1 and F2 females displayed decreased licking while spending more time resting alone. F1 RNAseq showed a reduction in Th, Drd1 and Drd2 mRNA expression. These alterations on maternal behavior are known to cause transgenerational alterations of the development of the corticotropic and gonadotropic axis.

In conclusion, exposure to an environmentally relevant EDC mixture transgenerationally affects sexual development and reproduction throughout epigenetic reprogramming of the hypothalamus. While not yet clear, such effects could be mediated by alterations of maternal behavior caused by exposure to the first generation.

ReferenceImage.

DES and the GENES