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the afternoon of proestrus was as low in the PCB exposed groups as the EB exposed
group, an observation indicative of the failure to generate a preovulatory GnRH
surge via steroid positive feedback. Corroborating indices of masculinization
included male-typical AVPV volume in both PCB exposed groups, and male-like
levels of ER
-ir neurons in the A1221 exposed group. Intriguingly, luteinizing hor-
mone (LH) levels were signifi cantly attenuated in the A1221 exposed group, but not
the PCB mixture group, despite signifi cantly impaired GnRH activation in the latter
group. It remains to be determined what the compensatory mechanism for this,
resulting in normal LH levels, might be.
α
Males
In contrast to females, effects of gestational PCB exposure were relatively mild in
adult males. AVPV/PeN kisspeptin-ir was unaltered as were AVPV ER
cell num-
bers. Serum testosterone levels were signifi cantly depreciated in the group exposed
to the PCB mixture but not EB or A1221. Serum progesterone levels, however, were
signifi cantly lower in both PCB groups but unaltered by EB, suggesting an alterna-
tive mechanism of action for this endpoint. Notably, male puberty was delayed by
PCB exposure, an effect which may indicate disruption of ARC kisspeptin signaling
pathways. This possibility remains to be examined.
Importantly, the dose of Aroclor used for these two studies has previously been
shown to produce reproductive effects in female rats [
113
,
114
], and the dose of
PCB congeners approximates the typical body burden of human infants [
107
,
115
].
Because these exposure levels employed for these studies are considered to be
human relevant [
113
,
114
,
116
], these results raise the possibility that the human
kisspeptin system may be vulnerable to disruption by exposure to PCBs and other
EDCs at current exposure levels (Table
21.2
).
α
I n fl uence of Genistein and other Phytochemicals
on the Kisspeptin System
Considering that kisspeptin neurons are likely a critical component of a complex
neural network tuned by evolutionary forces to coordinate reproductive activity in
response to a milieu of environmental cues [
117
,
118
], it is arguably expected that
this system should be sensitive to phytoestrogens. Research spanning six decades
has established that phytoestrogens interfere with the organizational role of endog-
enous estrogen in the developing mammalian reproductive system [
19
]. Very lim-
ited data, however, regarding the impact of phytoestrogens on kisspeptin signaling
networks has been generated thus far. These studies have primarily used approaches
similar to those described for BPA and the PCBs, which focus on the impacts of
acute exposure over discrete developmental periods.
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