| Autor: |
Adekunbi DA; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.; Department of Physiology, College of Medicine, University of Lagos, Lagos, Nigeria., Li XF; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., Li S; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., Adegoke OA; Department of Physiology, College of Medicine, University of Lagos, Lagos, Nigeria., Iranloye BO; Department of Physiology, College of Medicine, University of Lagos, Lagos, Nigeria., Morakinyo AO; Department of Physiology, College of Medicine, University of Lagos, Lagos, Nigeria., Lightman SL; Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom., Taylor PD; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., Poston L; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom., O'Byrne KT; Division of Women's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. |
| Abstrakt: |
To investigate the mechanism by which maternal obesity disrupts reproductive function in offspring, we examined Kiss1 expression in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei, and posterodorsal medial amygdala (MePD) of pre-pubertal and young adult offspring. 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 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 MePD of males. The role of MePD kisspeptin on puberty, estrous cyclicity and preovulatory LH surges 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 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 the MePD plays a key role in pubertal timing and ovulation and that maternal obesity may act via amygdala kisspeptin signaling to influence reproductive function in the offspring. |
