It is well established that
estrogen administration during neonatal development can advance pubertal onset and prevent the maintenance of regular estrous cycles in female rats. This treatment paradigm also eliminates the preovulatory rise of
gonadotropin releasing hormone (
GnRH). It remains unclear, however, through which of the two primary forms of the
estrogen receptor (
ERalpha or
ERbeta) this effect is mediated. It is also unclear whether endocrine disrupting compounds (EDCs) can produce similar effects. Here we compared the effect of neonatal exposure to
estradiol benzoate (EB), the
ERalpha specific agonist
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), the
ERbeta specific agonist
diarylpropionitrile (
DPN) and the naturally occurring EDCs
genistein (GEN) and
equol (EQ) on pubertal onset, estrous cyclicity,
GnRH activation, and
kisspeptin content in the anteroventral periventricular (AVPV) and arcuate (
ARC) nuclei. Vaginal opening was significantly advanced by EB and GEN. By 10 weeks post-puberty, irregular estrous cycles were observed in all groups except the control group.
GnRH activation, as measured by the percentage of immunopositive
GnRH neurons that were also immunopositive for Fos, was significantly lower in all treatment groups except the
DPN group compared to the control group.
GnRH activation was absent in the PPT group. These data suggest that neonatal exposure to EDCs can suppress
GnRH activity in adulthood, and that
ERalpha plays a pivotal role in this process.
Kisspeptins (KISS) have recently been characterized to be potent stimulators of
GnRH secretion. Therefore we quantified the density of KISS immunolabeled fibers in the AVPV and
ARC. In the AVPV, KISS fiber density was significantly lower in the EB and GEN groups compared to the control group but only in the EB and PPT groups in the
ARC. The data suggest that decreased stimulation of
GnRH neurons by KISS could be a mechanism by which EDCs can impair female reproductive function.