The study is the beginning to demonstrate that the actual physical organization of a region of the brain that is important for female reproduction can be significantly altered by exposure to phytoestrogens - or plant-produced chemicals that mimic hormones - during development. Specifically, the study finds that the compounds alter the sex-specific formation of the hypothalamus - a brain region that is essential to the regulation of puberty and ovulation. The study also shows that the phytoestrogens could case long-term personal effects on the female reproductive system.
While the study examined the impact of these compounds on laboratory rats, neurotoxicologist Dr. Heather Patisaul - world Health Organization co-authored the study - says the affected "circuitry" of the brain is similar in both rats and humans. Patisaul is an help professor in NC State's Department of Zoology. Her co-author is Heather Bateman, a doctoral student in the department.
Patisaul says this finding is extremely important because, piece the changes in brain structure cannot be reversed, "if you understand what is broken, you english hawthorn be capable to treat it." Patisaul says she is in the process of evaluating the personal effects of these compounds on the ovaries themselves.
Patisaul says that this study is also "a step towards ascertaining the effects of phytoestrogens on developing fetuses and newborns." Patisaul adds that these phytoestrogenic compounds cross the placental barrier in humanity and that, while many people are concerned about the personal effects of semisynthetic compounds on human wellness, it is important to note that some naturally occurring substances can let similar effects.
In the study, which will be published in an upcoming number of Neurotoxicology, the researchers exposed newborn rats to physiologically relevant doses of the phytoestrogens genistein and equol, and then looked at procreative health markers in the rats throughout their adulthood. The neonatal stage of development in rats is comparable to the latter stages of pregnancy for humans, Patisaul says. Genistein is a phytoestrogen that is set up in respective plants, including soybeans and soy-based foods. Equol is a hormone-like compound that is formed when bacteria found in the digestive system metabolize another phytoestrogen. However, only approximately a third of humans have the necessary bacteria to produce equol.
The study shows that both genistein and equol resultant role in the early interruption of the rats' oestrus cycle - which would be corollary to early onset of menopause in a human. The study also showed that genistein caused the early oncoming of puberty. The dislocation of the estrus cps could stalk from problems with the brain or the ovaries, so the researchers distinct to determine if the compounds had any result on brain development or function.
Patisaul explains that the brains of both female rats and female man have a region that regulates ovulation. "That constituent of the brain," Patisaul says, "is organized by hormones during development - which is the neonatal stage for rats and during pregnancy for humans." Patisaul says the new study shows that the female brain is "critically sensitive" to genistein and equol during this crucial stage of development - and that this may indicate that the encephalon is as well especially sensitive during this period to all phytoestrogens and perchance other man-made chemicals, such as bisphenol-A.
Abstract:
"Disrupted female reproductive physiology next neonatal exposure to phytoestrogens or estrogen specific ligands is associated with decreased GnRH activation and kisspeptin fiber denseness in the hypothalamus"
Authors: Dr. Heather B. Patisaul, Heather L. Bateman, North Carolina State University
Published: July 2008, online by Neurotoxicology
It is well established that estrogen administration during neonatal growing can advance pubertal onrush and keep the maintenance of regular estrous cycles in female rats. This treatment paradigm also eliminates the preovulatory rise of gonadotropin cathartic hormone (GnRH). It remains unclear, notwithstanding, through which of the two elementary forms of the oestrogen receptor (ER? or ER?) this outcome is mediated. It is also unclear whether endocrine disrupting compounds (EDCs) tin can produce like effects. Here we compared the upshot of neonatal exposure to estradiol benzoate (EB), the ER? specific agonist 1,3,5-tris(4-Hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), the ER? specific agonist diarylpropionitrile (DPN) and the course occurring EDCs genistein (GEN) and equol (EQ) on pubertal onrush, estrous periodicity, GnRH energizing, and kisspeptin content in the anteroventral periventricular (AVPV) and bowed (ARC) nuclei. Vaginal opening move was significantly advanced by EB and GEN. By ten weeks postpuberty, irregular estrous cycles were ascertained in all groups except the restraint group. GnRH activation, as measured by the pct of immunopositive GnRH neurons that were also immunopositive for Fos, was significantly lower in all treatment groups demur the DPN group compared to the control group. GnRH activation was wanting in the PPT radical. These data suggest that neonatal exposure to EDCs can suppress GnRH activity in adulthood, and that ER? plays a polar role in this process. Kisspeptins (KISS) have of late been characterized to be potent stimulators of GnRH secretion. Therefore we quantified the concentration of KISS immunolabeled fibers in the AVPV and ARC. In the AVPV, KISS fibre density was significantly glower in the EB and GEN groups compared to the control group but only in the EB and PPT groups in the ARC. The information suggest that decreased stimulation of GnRH neurons by KISS could be a mechanism by which EDCs can impair female procreative function.
Source: Matt Shipman
North Carolina State University
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