Role of amydala kisspeptin in pubertal timing in female rats

To investigate the mechanism by which maternal obesity disrupts reproductive function in the offspring, the present study examined Kiss1 mRNA expression in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei, and the posterodorsal medial amygdala (MePD) of pre-pubertal and young adult offspring. Female Sprague-Dawley rats were fed either a standard or energy-dense diet for six weeks prior to mating and throughout pregnancy and lactation. Male and female offspring were weaned onto a normal diet on postnatal day (pnd) 21. Brains were collected on pnd 30 or 100 for qRT-PCR to determine Kiss1 mRNA levels. Maternal obesity increased Kiss1 mRNA expression in the MePD of pre-pubertal male and female offspring, whereas Kiss1 expression was not affected in the ARC or AVPV at this age. Maternal obesity reduced Kiss1 expression in all three brain regions of 3 month old female offspring, but only in the MePD of male offspring. The role of MePD Kiss1 on puberty onset, estrous cyclicity and the preovulatory LH surge was assessed directly in a separate group of post-weanling and young adult female rats exposed to a normal diet throughout their life course. Bilateral intra-MePD cannulae connected to osmotic mini-pumps for delivery of kisspeptin receptor antagonist (Peptide 234; 2nmol in 6µl/d for 14 days) were chronically implanted on pnd 21 or 100. Antagonism of MePD kisspeptin delayed puberty onset, disrupted estrous cyclicity and reduced the incidence of LH surges. These data show that MePD Kiss1 plays a key role in pubertal timing and ovulation and that maternal obesity may act via amygdala Kiss1 signaling to influence reproductive function in the offspring.