Biology Reference
In-Depth Information
drought, and extreme temperatures. As such, at high levels they are a signal of poor
environmental conditions and thus convey important information about when it might
be an optimal time to invest in reproduction. Not surprisingly, a high level of phytoes-
trogen intake has been shown to suppress ovulation and fertility, even in humans [ 19 ].
Sheep raised on legume-rich pastures develop a well-characterized suite of reproduc-
tive pathologies resulting in reduced conception rates and embryonic loss [ 9 - 11 ].
Recognized since the 1940s, this syndrome is called “clover disease” and can be ame-
liorated by rearing the animals on subterranean clover cultivars that produce fewer
phytoestrogens. Prolonged exposure, however, can ultimately result in permanent infer-
tility, even in adult ewes [ 25 ]. Other features of clover disease include estrous cycle
irregularity, pyometra, endometrial hyperplasia, leiomyoma of the cervix and uterus,
and cystic ovaries. These effects highlight that exposure to inappropriate levels, or
during particularly vulnerable windows of development, can result in deleterious effects.
Human reproductive physiology is also responsive to phytoestrogens. Menstrual cycle
irregularities have been reported in humans consuming a soy-rich diet [ 16 ] and use of
soy-based infant formula has been associated with a higher risk of menstrual cycle
disorders and uterine fi broids in young women [ 33 , 34 ]. Anthropogenic EDCs likely
exploit these evolved systems for sensing external cues of environmental quality,
resulting in similar pathologies. Investigation of the specifi c mechanisms by which syn-
thetic and naturally occurring EDCs act to affect vertebrate physiology has now begun
to hone in on the kisspeptin system because it is rapidly becoming clear that it is an
essential driver of reproductive maturation and function across species.
Exploration of how EDCs perturb the organization and function of the kisspeptin sys-
tem has proven to be a useful approach for the kisspeptin fi eld in general because it yields
both critical information about the underlying mechanisms contributing to EDC pathol-
ogy, but also how this system responds to ecologically relevant environmental cues across
the life span. Because a core element of EDC research is the timing-specifi c consequences
of exposure, to date, most of the work on the kisspeptin system within this fi eld has focused
on the long-term, sex-specifi c, impacts of perinatal exposure. This research has already
begun to identify species, age, and sex-specifi c sensitivities to endogenous hormones and
EDCs within kisspeptin signaling pathways across different life stages. As the fi eld grows,
it will ultimately yield a wealth of information about how species differences in the kiss-
peptin system may have evolved, and a better understanding of how this system responds
to ecologically relevant environmental cues across the life span.
Kisspeptin System Endocrine Disruptors: Bisphenol A,
Polychlorinated Biphenyls, and Genistein
Although they are now recognized to have multiple modes of action within the
endocrine system, EDCs are thought to act, primarily, by interfering with steroid
hormone signaling. The subclass of EDCs that has been most comprehensively
studied is the group which acts on nuclear estrogen receptors (ERs) (for detailed
reviews, see [ 16 , 35 - 37 ]). This group contains many well-known EDCs, including
Search WWH ::




Custom Search