Bugs in the program: can pregnancy drugs and smoking disturb molecular reprogramming of the fetal germline, increasing heritable risk for autism and neurodevelopmental disorders?
2018 Study Abstract
In a seeming paradox, the prevalence of autism spectrum disorder (ASD) has surged, while at the same time research has pointed to the strong heritability of this neurodevelopmental pathology. Here an autism research philanthropist suggests a biological phenomenon of exogenously induced ‘gamete disruption’ that could reconcile these seemingly contradictory observations. Mining information from her own family history and that of her fellow autism parents, while also engaging with the scientific community, she proposes that a subset of the autisms may be rooted in a variety of molecular glitches in parental gametes induced by certain acute exposures during the parents’ own fetal or neonatal development. These exposures include but are not limited to synthetic hormone drugs, tobacco, and general anesthesia. Consistent with this hypothesis, animal models have demonstrated adverse neurobehavioral outcomes in grandoffspring of gestating dams exposed to hormone-disrupting compounds, tobacco components, and general anesthesia. A recent epidemiological study showed a link between grandmaternal smoking and risk for ASD in grandoffspring through the maternal line. Given the urgency of the autism crisis, combined with the biological plausibility of this mostly unexplored paradigm, the writer contends that questions of nongenetic inheritance should be a priority in autism research.
Read the full study (free access) Bugs in the program: can pregnancy drugs and smoking disturb molecular reprogramming of the fetal germline, increasing heritable risk for autism and neurodevelopmental disorders? on Oxford University Press, Environmental Epigenetics, Volume 4, Issue 2, 26 April 2018.
Help Fund Research into Neurodevelopment and Behavioral Impacts of DES
” My name is Jill Escher. I’m a science philanthropist who kickstarts pioneering research projects investigating the generational toxicity of certain potent exposures, including DES, tobacco and other drugs. While I’m not a DES daughter, I was exposed to a multitude of other synthetic steroid hormones in utero as part of a then-popular, if ineffective, “anti-miscarriage” practice. You can read my story here. You can see my science website at GermlineExposures.org.
Based on human, animal, and in vitro studies, as well as family interviews, I hypothesize that diethylstilbestrol DES, along with several other toxic substances, can damage the genomic information in early fetal-stage gametes. For a variety of reasons, the early gamete is probably the single most vulnerable stage of the human lifecycle. Damage during that phase, which could be genetic or epigenetic in nature, can manifest as abnormal development in the subsequent offspring.
For example, I hypothesize that the intensive synthetic steroid hormone drug regimen to which I was subjected as a fetus subtly deranged the molecular programming of my early eggs. This derangement I believe resulted in the starkly abnormal neurodevelopment — autism — of my children. I have met many other families with the same story.
Support Research into the Far-Reaching Generational Toxicity of DES, germline exposures, 10/10/2016.
I am pleased to announce that I am funding the world’s first research study into the grandchild effects of DES (3d gen), looking specifically at neurodevelopment and behavioral impacts. This work will be done in collaboration with Harvard University, based on the Nurses’ Health Study II.
Thank you for your support! If you have any questions, please do not hesitate to email me. “
Jill Escher, President of Autism Society San Francisco Bay Area, 10/10/2016.
Emilie Rissman PhD, interviewed by Jill Escher, 2014
Emilie Rissman, PhD, Professor of Biochemistry & Molecular Genetics, University of Virginia, studies mammalian behavioral genetics. Because many social behaviors are activated only when gonadal steroid hormones are present, the genes for steroid hormone receptors are currently under study in her lab. She has found that androgen receptor is required for normal social affiliative behavior in male mice. In addition, her work shows that several social behaviors are sexually dimorphic, in part, because of differences in sex chromosome genes. Her work in mice is relevant to several sexually dimorphic neurobehavioral diseases including autism spectrum disorder.
Dr. Rissman, I’m very pleased to be interviewing you because since you are one of the few researchers to explicitly examine multigenerational effects of endocrine disruption as it relates to abnormal behavior and neurodevelopment in offspring. How did you come to examine this question?
How did gestational BPA exposure differentially affect succeeding generations?
What epigenetic mechanisms are at play with exposure to EDCs?
What do we know about hormone and other receptors on and in germ cells? And somatic cells, if there’s a difference.
What role does the steroid hormone receptor play in epigenetic function?
Why do hormone-disrupting molecules affect epigenetic activity?
Some of the scientists I’ve spoken with differentiated between “strong” exposures and weak ones in terms of likelihood of epigenetic impacts. Some strong ones mentioned included steroid hormones and their mimics, cigarette smoke and psychoactive drugs. Comparatively weak ones were thought to include variability in stress and nutrition. Do you agree with this general distinction?
It seems we forget there’s a long and complicated molecular phase of the human life cycle. For example, those who say BPA or pesticides are safe cite studies on adults, children or fetuses. But isn’t the most vulnerable phase gametes and precursor cells? What do you consider to be important windows of vulnerability? While nearly all scientists find endocrine disruption a concern, some say “there’s just not enough evidence yet” to be concerned about ambient exposures. How do you respond to that? What would be “enough” evidence?
Video published on 11 Aug 2014 by AncestryFoundation
Speaker Jill Escher, mother of two children with autism, will also share her experience as a member of the “guinea pig generation” heavily exposed in utero to novel synthetic drugs popular in the 1960s. Learn more about the work of the Escher Fund at Germline Exposures.
By now most of us know gene expression can be upregulated or downregulated by molecular factors including the metabolites of drugs, chemicals and nutrition. But what are the implications of this environmentally labile landscape, not only for our somatic (body) cells, but also our germ cells, which contain our genetic and epigenetic molecules of inheritance? In this presentation by a science philanthropist (Escher Fund for Autism) who focuses on cutting-edge gene-environment interaction research, you will learn: • How genes respond to environmental cues.
How evolutionary concepts are broadening to include environmental responsivity of genes and the germline.
How, from a biological point of view, the human lifecycle begins about 20-40 years before conception with the dynamic, complex, and lengthy molecular phase of germline (egg and sperm) development.
How, in light of the true breadth of the human lifecycle, risks of exposures are routinely underestimated.
How ancestral health principles are critical to reducing pervasive and serious risks, and improve health across the generations.
by Jane Kay, feat. Jill Escher “Autism Exposed” interview
” Three years ago, Jill Escher had an epiphany, one that now consumes her waking hours and night time dreams. After prodding her mother for clues from her past, Jill discovered some hidden history: Her mother had sought help conceiving at a fertility clinic. As she grew in her mother’s womb, Jill was bombarded with synthetic hormones and other drugs.
Now Jill Escher‘s dogged quest to unravel why this happened to her children has drawn the attention of scientists, and may ultimately lead to a greater understanding of how prescription drugs — and perhaps chemicals in the environment — may secretly and subtly harm the health of generations to come. ”