The neuroscience behind gender development iii

The Neuroscience behind Gender Development

The Effects of Endocrine Disruptors in Early Sexual

BY CHRIS VETRANO Development THE DEVELOPMENT OF GENDER HDV-283104-01

T he Neuroscience behind Gender Development The Effects of Endocrine Disruptors in Early Sexual Development

Are EDCs Blurring Issues of Gender? “Although scientists have postulated a wide range of adverse human health effects of exposure to endocrinedisrupting chemicals (EDCs), the nexus of the debate is the concern that prenatal and childhood exposure to EDCs may be responsible for a variety of abnormalities in human sexuality, gender development and behaviors, reproductive capabilities, and sex ratios.” (Hood, 2005)

Introduction The amount of evidence, that has been uncovered through scientific research, is proving Endocrine Disruptor Chemicals (EDC’s) are causing “Disorders of Sex Development” (DSD), at early stages of brain development. I think it is important to understand how neuroscience can help us see gender at a neuronal level and by studying the developmental stages of gender, we can see a neurological correspondence, as it applies to activity in the brain. Abnormal hormonal signals, disrupted in early stages of brain development, cause imbalances in hormonal levels.

“Endocrine disruptors are chemicals that may interfere with the body’s endocrine system and produce adverse developmental, reproductive, neurological, and immune effects in both humans and wildlife. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption.” (National Institute of Environmental Health Sciences, 2014) In early development, during the intrauterine period, “the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge.” (Savic, Garcia-Falgueras, Swaab, 2010) Research shows that EDC’s cause the most significant problems “during prenatal and early postnatal development when organ and neural systems are forming.” (National Institute of Environmental Health Sciences, 2014) The process of “sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result

“For males and females alike, the entire process of reproductive development is exquisitely sensitive to minute changes in levels of the sex hormones, particularly during certain critical windows of development.” (Hood, 2005)

in transsexuality.” (Savic, Garcia-Falgueras, Swaab, 2010) As has been demonstrated in the book As Nature Made Him by John Colapinto, serious issues arise when the brain does not match the body. “In the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain.” (Savic, Garcia-Falgueras, Swaab, 2010) There have also been studies regarding such cases and the evidence seems to side with Nature rather than Nurture. In other words, if you are born a boy and had gender reassignment to become a girl, the chances of you displaying male-typical behaviors is high.

These studies suggest there is the possibility that a large percentage of recent cases of DSD’s, may be caused by EDC’s. The amount of toxin that needs to be present for alterations and imbalances in hormonal distribution is low and the consequences can be permanent. “During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult.” (Bigsby, 1999) Others continue to clarify that hormones are a determining factor in gender development and must be recognized. "The different regions of the brain develop in a different sequence, and different tempo, in girls compared with boys" (Sax, 2010) There are many studies that can attest to this. "Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests."

(Hines, 2011) This paper looks to uncover the truth about EDC’s and The Effects of Endocrine Disruptors in Early Sexual Development.

Early Brain/Sexual Development It is important to understand that the brain regulates neuroendocrine functions, it is also very responsiveness to hormonal feedback, this makes it an obvious place to start in understanding how EDC’s affect early development. (Gore, 2007) “Vertebrates have two systems responsible for communication in the body: the nervous system and the endocrine system. The brain is not only the major regulatory element for both but also a mediator between the two systems. The brain coordinates inputs from the environment with hormonal outputs from the endocrine system through the autonomic nervous system. Endocrine glands in the body are innervated by the autonomic nervous system, which controls glandular function in two ways: (i) by regulating blood flow into the gland and (ii) by regulating the release of hormones from the gland.” (Gore, 2007) There is ample evidence that EDC’s are part of the etiology of many disorders which include infertility, diabetes, obesity, the metabolic syndrome, allergies, immunodeficiency and cancer.

(Kajta, Wójtowicz, 2013) One example is, bisphenol A and TCDD “abrogated differences between female and male brains in respect to locus coeruleus and hypothalamic preoptic area.

Prenatal exposure to phthalates and bisphenol A were associated with change of sex-specific behavior in 2-year-old girls. It has been postulated that the effects of EDCs on the brain and behavior are attributed to hormone receptor – mediated actions.” (Kajta, Wójtowicz, 2013) The brain is sexually dimorphic, this means there are specific differences in structure and morphology of regions between males and females. These differences are determined during a crucial time in sexual differentiation, sex steroid hormones are generated in fetal development or shortly after birth. “In male mammals, much of sexual differentiation of the brain occurs through activation of the fetal testis to release the testicular hormone testosterone. Testosterone and its metabolite, E2, are responsible for sexual differentiation of the male brain.” (Gore, 2007) This means early exposure to estrogenic/antiestrogenic and androgenic EDCs can have serious adverse effects to brain function from genes to behavior. (Gore, 2007) The fetus is extremely sensitive to even the smallest shift in the hormonal milieu and although the levels of hormones required during this time to make these changes are low the slightest imbalance is enough to have serious consequences. (Gore, 2007) “Evidence that the brain may be an important target of these compounds, and therefore early exposure, particularly through consumption of soy formula, may be relevant to neurodevelopment.” (Gore, 2007)

Endocrine Disruptors EDC’s are associated with both natural and manmade products, (phytoestrogens such as soy, alfalfa, and clover), pesticides [dichlorodiphenyl-trichloroethane (DDT)], fungicides (vinclozolin), substances used in production of plastics or as plasticizers (bisphenol A and phthalates), industrial chemicals [polychlo-rinated biphenyls (PCBs)], and metals (cadmium, lead, mercury, and uranium and arsenic, a metalloid. (Gore, 2007) According to the U.S. Environmental Protection Agency (EPA) Endocrine-disrupting compounds are “an exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction, and developmental process.” (Diamanti, Kandarakis et al., 2009) EDCs imitate, block, alter, or otherwise modify endogenous hormonal activity. EDC’s not only affect the reproductive system but have now been recognized to cause hormonal systems in the body to malfunction including thyroid, growth, and other metabolic hormones. (Gore, 2007) “Endocrine hormones are essential for the normal development and function of the central nervous system (CNS). The prenatal and early postnatal period is particularly important in this regard as exposure to hormones during early development results in the normal organization and facilitation of many behaviors in the adult organism.” (Gore, 2007)

Consequences of EDC’s on Sexual Development The increase in EDC’s from manmade chemicals are essentially causing an imbalance of the naturally occurring compounds. As industry avoids responsibility, primarily by using independent studies to countermeasure the truth found in all other studies, the effects of EDC’s is alarmingly evident and causing many problems to animals and humans. (De Guerre, 2008) “Over

the past four decades, human sperm counts have been markedly decreasing and the rate of testicular cancer rates has risen. Meanwhile, the occurrence of undescended testicles and abnormally developed male urethras are also thought to be increasing.” (Society for Endocrinology, 2014) Cellular function is disrupted when there is a change in protein levels in the brain caused by organochlorine pesticides thereby altering the expression of numerous neuronal genes. (Gore, 2007) “Recently, evidence has been published that embryonic exposure to methoxychlor can alter the reward circuitry in the female rat. This circuitry is known to be sexually dimorphic.” (Gore, 2007) Of the studies currently being done on humans and wildlife there is significant evidence affirming the adverse reproductive and sexual development of both.

“Reproductive alterations in wildlife, decreases in human sperm counts, morphological anomalies in genitalia, and an increasing trend in testicular and prostatic cancers are all putative effects in response to EDC exposure.” (Cowin, Foster, Risbridger, 2007) In a study of young Puerto Rican girls with premature breast development there was evidence of high levels of EDC’s present in their blood serum. “Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.” (Colón, Caro, Bourdony, 2000) Clearly the evidence is sufficient enough to at least begin phasing these chemicals out of our environment. One need only look in their own homes to identify the numerous EDC’s that surround us on a daily basis. Gender is being altered to such a degree that finding a common ground between us is becoming more difficult every day. There is too much evidence that EDC’s are the cause of abnormal gender development to argue otherwise. We are altering the fabric of life on so many levels these days, it will be interesting to see how these changes affect us over time. As it stands right now perpetuating the production of EDC’s should be a cause for concern.

References Bigsby, R., Chapin, R. E., Daston, G. P., Davis, B. J., Gorski, J., Gray, L. E., . . . Howdeshell, K. L. (1999, August). Evaluating the effects of endocrine disruptors on endocrine function during development. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567510/

Col贸n, I., Caro, D., Bourdony, C. J., & Rosario, O. (2000). Identification of Phthalate Esters in the Serum of Young Puerto Rican Girls with Premature Breast Development. Retrieved May 1, 2014, http://helios.hampshire.edu/~cjgNS/sputtbug/416K/EndoDisruptors/Thalate.pdf De Guerre, M. (Director). (2008). The Disappearing Male [Motion picture]. Canada: Optix Digital Pictures.

Diamanti-Kandarakis, E., Bourguignon, J., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., . . . Gore, A. C. (2009). Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocrine Reviews. doi:10.1210/er.2009-0002 Gore, A. C. (2007). Endocrine-disrupting chemicals: From basic research to clinical practice.

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