Third Floor Lecture Hall, Jianzan Building (Phase I)
Chinese Institute for Brain Research, Beijing
10:30-11:00 Monday，October 28th, 2019
William Henry Colledge, Ph.D.
Physiology, Development and Neuroscience
University of Cambridge
William Henry Colledge，博士
Dr. Magdalena J Koziol
Infertility affects around 10-14% of couples globally and can significantly impact on the quality of life and the mental health of the individuals involved. Kisspeptins, a set of overlapping neuropeptides encoded by the Kiss1 gene, were originally identified as having an anti-metastatic activity in several cancer cell lines. It is now known, however, that kisspeptin is a key regulator of the mammalian reproductive axis and is required to initiate puberty by stimulating the release of gonadotropin stimulating hormone (GnRH) from the hypothalamus. Mice and humans with mutations in the kisspeptin signalling pathway have hypogonadotropic hypogonadism and are infertile. In addition to its role in puberty, kisspeptins are also required for ovulation. Indeed, analogues of kisspeptin are now being used as a potentially safer hormone regime to induce ovulation in women as part of in vitro fertilization treatments. Kiss1 neurons are found in two main areas of the hypothalamus: the arcuate (ARC) region, which regulates basal GnRH pulsatility and the anteroventral periventricular (AVPV) region, which controls the preovulatory LH surge. Kiss1 neurons are capable of integrating a variety of physiological signals to modulate the reproductive axis depending upon nutrition and environmental inputs. For example, it is thought that increased adiposity in young children and the action of leptin on kisspeptin expression can contribute to premature puberty in obese children. To understand better how the reproductive axis is regulated by these factors we have been mapping the neuronal circuitry into Kiss1 neurons. Several of these neuronal connections have been implicated as physiologically relevant in regulating the reproductive axis such as from the suprachiasmatic nucleus to control circadian ovulation. Moreover, kisspeptins have also been implicated in actions outside the brain such as a role in glucose metabolism, placentation and pregnancy. Thus, a full understanding of the physiological actions of kisspeptins and how they are regulated is vital to improving human reproductive health.
不孕症困扰了全球大约10-14％的夫妇，严重影响了他们的生活质量和心理健康。 亲吻素神经肽Kisspeptins是由Kiss1基因编码的存在重叠区域的一组神经肽，最初被鉴定为在几种癌细胞系中具有抗转移活性。然而，现已知亲吻素神经肽是哺乳动物生殖轴的关键调节因子，并且可以刺激下丘脑促性腺激素释放激素（GnRH）的释放来开启青春期。对于小鼠和人类，亲吻素神经肽信号通路上存在的突变会导致促性腺激素分泌不足的性腺功能减退甚至是不育症。除了对青春期的作用外，亲吻素神经肽也是排卵所必需的。实际上，在体外受精治疗时，亲吻素神经肽类似物现在被用作可能更安全的激素方案以诱导女性排卵。 Kiss1神经元存在于下丘脑的两个主要区域：调节GnRH的基本脉冲式释放的弓状核（ARC）和控制排卵前LH（黄体生成素）波动的前腹侧室周核（AVPV）。 Kiss1神经元能够根据营养和环境的输入来整合各种生理信号进而调节生殖轴。例如，人们认为儿童肥胖的增加和瘦蛋白对亲吻素神经肽表达的影响可能导致肥胖儿童过早进入青春期。为了更好地理解这些因素如何调节生殖轴，我们探究了Kiss1神经元的神经环路，发现一些神经连接可调节生殖轴，比如视交叉上核可以控制节律排卵，例如。此外，亲吻素神经肽在大脑外也有重要作用，例如葡萄糖代谢，胎盘形成和妊娠。因此，充分了解亲吻素神经肽的生理作用及其调节机制对于改善人类的生殖健康至关重要。
Professor William Colledge is joint Head of Department and Professor of Reproductive Physiology in the Department of Physiology, Development and Neuroscience (PDN) at the University of Cambridge. He obtained his BSc from Imperial College, London and his PhD from the National Institute for Medical Research, London. After a post-doctoral position in Ottawa, Canada, he joined the laboratory of the Nobel Prize winner Prof Sir Martin Evans in Cambridge. He then worked in the Gurdon Institute before he was appointed as a University Lecturer in the Department of Physiology, which merged with the Anatomy Department to form PDN. Professor Colledge teaches reproductive physiology and endocrinology to Medical, Veterinary and Natural Science Students.
Prof Colledge is an expert in the manipulation of mouse embryonic stem cells and the generation of transgenic mice. He has published 185 peer-reviewed publications and his h-index is currently 55 (ISI Web of Science). During his career, he has generated several important transgenic mouse models of human disease including cystic fibrosis and cardiac arrhythmias. His work with cystic fibrosis lead to Phase I clinical trials in the UK to evaluate a gene therapy treatment. His current research is focussed on understanding the neuroendocrine regulation of mammalian reproduction. His laboratory has played a major role in understanding the molecular events in the brain that are required for puberty and fertility. He has acted as a scientific consultant for several pharmaceutical companies including Paradigm Therapeutics, Takeda, Medimmune and Alloy Therapeutics.