Date of Award
Master of Science
Dr. Michael Lehman
Women with polycystic ovarian syndrome (PCOS) and prenatal testosterone (T)-treated ewes show similar reproductive neuroendocrine defects, including reduced responsiveness to feedback control of GnRH secretion, suggesting alterations in the hypothalamic circuitry mediating control of reproduction. KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) play a critical role in relaying the influence of steroid hormones to GnRH neurons. We tested the hypothesis that prenatal T exposure alters the synaptic connections of KNDy cells and their connections to GnRH neurons by examining inputs to kisspeptin and GnRH neurons in control and prenatal T- treated adult ewes. Prenatal T-treated animals showed a significant reduction in the total numbers of synaptic inputs onto ARC kisspeptin (KNDy) neurons, kisspeptin cells in the preoptic area (POA) and GnRH neurons in the medial basal hypothalamus (MBH) and POA. We also examined the effects of prenatal T treatment on the size of KNDy cell bodies and found that prenatal T ewes showed a significant increase in the somal size of KNDy cells compared to control ewes. Overall, prenatal T treatment results in morphological changes both in the synaptology of the KNDy population and its connections to GnRH, as well as its cell size. These changes may contribute to defects in the ability of the KNDy population to convey steroid feedback signals to GnRH neurons.
Cernea, Maria, "EFFECTS OF PRENATAL TESTOSTERONE ON KNDY- GNRH CIRCUITRY IN A SHEEP MODEL OF PCOS" (2011). Digitized Theses. 3349.