{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:20:43Z","timestamp":1764588043373,"version":"3.37.3"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Manatu Hauora | Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18-671","18-671"],"award-info":[{"award-number":["18-671","18-671"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prenatal androgen excess is suspected to contribute to the development of polycystic ovary syndrome (PCOS) in women. Evidence from preclinical female animal models links maternal androgen excess with the development of PCOS-like features and associated alterations in the neuronal network regulating the reproductive axis. There is some evidence suggesting that maternal androgen excess leads to similar reproductive axis disruptions in men, despite the critical role that androgens play in normal sexual differentiation. Here, the specific impact of maternal androgen excess on the male hypothalamic-pituitary-gonadal axis was investigated using a prenatal androgenization protocol in mice shown to model PCOS-like features in females. Reproductive phenotyping of prenatally androgenised male (PNAM) mice revealed no discernible impact of maternal androgen excess at any level of the reproductive axis. Luteinising hormone pulse characteristics, daily sperm production, plasma testosterone and anti-M\u00fcllerian hormone levels were not different in the male offspring of dams administered dihydrotestosterone (DHT) during late gestation compared to controls. Androgen receptor expression was quantified through the hypothalamus and identified as unchanged. Confocal imaging of gonadotropin-releasing hormone (GnRH) neurons revealed that in contrast with prenatally androgenised female mice, PNAM mice exhibited no differences in the density of putative GABAergic innervation compared to controls. These data indicate that a maternal androgen environment capable of inducing reproductive dysfunction in female offspring has no evident impact on the reproductive axis of male littermates in adulthood.<\/jats:p>","DOI":"10.1038\/s41598-019-55436-9","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T12:44:58Z","timestamp":1576068298000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The influence of maternal androgen excess on the male reproductive axis"],"prefix":"10.1038","volume":"9","author":[{"given":"Sarah","family":"Holland","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Prescott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pankhurst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-532X","authenticated-orcid":false,"given":"Rebecca E.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"55436_CR1","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1136\/bmj.301.6761.1111","volume":"301","author":"DJ Barker","year":"1990","unstructured":"Barker, D. J. The fetal and infant origins of adult disease. BMJ: British Medical Journal 301, 1111\u20131111 (1990).","journal-title":"BMJ: British Medical Journal"},{"key":"55436_CR2","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/S0093-691X(99)00258-7","volume":"53","author":"DJP Barker","year":"2000","unstructured":"Barker, D. J. P. In utero programming of cardiovascular disease. Theriogenology 53, 555\u2013574, https:\/\/doi.org\/10.1016\/S0093-691X(99)00258-7 (2000).","journal-title":"Theriogenology"},{"key":"55436_CR3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1126\/science.156.3772.258","volume":"156","author":"S Levine","year":"1967","unstructured":"Levine, S. Maternal and Environmental Influences on the Adrenocortical Response to Stress in Weanling Rats. Science 156, 258\u2013260, https:\/\/doi.org\/10.1126\/science.156.3772.258 (1967).","journal-title":"Science"},{"key":"55436_CR4","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1289\/ehp.951031136","volume":"103","author":"RM Sharpe","year":"1995","unstructured":"Sharpe, R. M., Fisher, J. S., Millar, M. M., Jobling, S. & Sumpter, J. P. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Environmental health perspectives 103, 1136\u20131143, https:\/\/doi.org\/10.1289\/ehp.951031136 (1995).","journal-title":"Environmental health perspectives"},{"key":"55436_CR5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1530\/rep.0.1220205","volume":"122","author":"SM Rhind","year":"2001","unstructured":"Rhind, S. M., Rae, M. T. & Brooks, A. N. Effects of nutrition and environmental factors on the fetal programming of the reproductive axis. Reproduction (Cambridge, England) 122, 205\u2013214 (2001).","journal-title":"Reproduction (Cambridge, England)"},{"key":"55436_CR6","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1210\/en.2004-1444","volume":"146","author":"T Steckler","year":"2005","unstructured":"Steckler, T., Wang, J., Bartol, F. F., Roy, S. K. & Padmanabhan, V. Fetal Programming: Prenatal Testosterone Treatment Causes Intrauterine Growth Retardation, Reduces Ovarian Reserve and Increases Ovarian Follicular Recruitment. Endocrinology 146, 3185\u20133193, https:\/\/doi.org\/10.1210\/en.2004-1444 (2005).","journal-title":"Endocrinology"},{"key":"55436_CR7","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1210\/en.2008-1256","volume":"150","author":"TL Steckler","year":"2009","unstructured":"Steckler, T. L., Herkimer, C., Dumesic, D. A. & Padmanabhan, V. Developmental Programming: Excess Weight Gain Amplifies the Effects of Prenatal Testosterone Excess On Reproductive Cyclicity\u2014Implication for Polycystic Ovary Syndrome. Endocrinology 150, 1456\u20131465, https:\/\/doi.org\/10.1210\/en.2008-1256 (2009).","journal-title":"Endocrinology"},{"key":"55436_CR8","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1210\/jc.2005-2757","volume":"91","author":"N Xita","year":"2006","unstructured":"Xita, N. & Tsatsoulis, A. Fetal Programming of Polycystic Ovary Syndrome by Androgen Excess: Evidence from Experimental, Clinical, and Genetic Association Studies. The Journal of Clinical Endocrinology & Metabolism 91, 1660\u20131666, https:\/\/doi.org\/10.1210\/jc.2005-2757 (2006).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"55436_CR9","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1093\/humrep\/17.10.2573","volume":"17","author":"T Sir-Petermann","year":"2002","unstructured":"Sir-Petermann, T. et al. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 17, 2573\u20132579 (2002).","journal-title":"Hum Reprod"},{"key":"55436_CR10","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/S0140-6736(97)06062-5","volume":"350","author":"JL Cresswell","year":"1997","unstructured":"Cresswell, J. L. et al. Fetal growth, length of gestation, and polycystic ovaries in adult life. The Lancet 350, 1131\u20131135, https:\/\/doi.org\/10.1016\/S0140-6736(97)06062-5 (1997).","journal-title":"The Lancet"},{"key":"55436_CR11","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s40618-017-0728-5","volume":"41","author":"R Cannarella","year":"2017","unstructured":"Cannarella, R., Condorelli, R. A., Mongioi, L. M., La Vignera, S. & Calogero, A. E. Does a male polycystic ovarian syndrome equivalent exist? Journal of endocrinological investigation 41, 49\u201357, https:\/\/doi.org\/10.1007\/s40618-017-0728-5 (2017).","journal-title":"Journal of endocrinological investigation"},{"key":"55436_CR12","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1210\/en.2012-2153","volume":"154","author":"F Connolly","year":"2013","unstructured":"Connolly, F. et al. Excess androgens in utero alters fetal testis development. Endocrinology 154, 1921\u20131933, https:\/\/doi.org\/10.1210\/en.2012-2153 (2013).","journal-title":"Endocrinology"},{"key":"55436_CR13","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1210\/er.2009-0023","volume":"31","author":"CA Christian","year":"2010","unstructured":"Christian, C. A. & Moenter, S. M. The Neurobiology of Preovulatory and Estradiol-Induced Gonadotropin-Releasing Hormone Surges. Endocrine reviews 31, 544\u2013577, https:\/\/doi.org\/10.1210\/er.2009-0023 (2010).","journal-title":"Endocrine reviews"},{"doi-asserted-by":"publisher","unstructured":"McArdle, C. & Perrett, R. Molecular Mechanisms of Gonadotropin-Releasing Hormone Signaling: Integrating Cyclic Nucleotides into the Network. Frontiers in Endocrinology 4, https:\/\/doi.org\/10.3389\/fendo.2013.00180 (2013).","key":"55436_CR14","DOI":"10.3389\/fendo.2013.00180"},{"doi-asserted-by":"crossref","unstructured":"Herbison, A. E. In Knobil and Neill\u2019s Physiology of Reproduction (Fourth Edition) 399\u2013467 (Academic Press, 2015).","key":"55436_CR15","DOI":"10.1016\/B978-0-12-397175-3.00011-9"},{"key":"55436_CR16","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1172\/jci108400","volume":"57","author":"R Rebar","year":"1976","unstructured":"Rebar, R. et al. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. The Journal of clinical investigation 57, 1320\u20131329, https:\/\/doi.org\/10.1172\/jci108400 (1976).","journal-title":"The Journal of clinical investigation"},{"key":"55436_CR17","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1210\/jcem.83.2.4604","volume":"83","author":"CL Pastor","year":"1998","unstructured":"Pastor, C. L., Griffin-Korf, M. L., Aloi, J. A., Evans, W. S. & Marshall, J. C. Polycystic Ovary Syndrome: Evidence for Reduced Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone1. The Journal of Clinical Endocrinology & Metabolism 83, 582\u2013590, https:\/\/doi.org\/10.1210\/jcem.83.2.4604 (1998).","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"55436_CR18","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1210\/jc.2004-2359","volume":"90","author":"S Chhabra","year":"2005","unstructured":"Chhabra, S. et al. Progesterone inhibition of the hypothalamic gonadotropin-releasing hormone pulse generator: evidence for varied effects in hyperandrogenemic adolescent girls. The Journal of clinical endocrinology and metabolism 90, 2810\u20132815, https:\/\/doi.org\/10.1210\/jc.2004-2359 (2005).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"55436_CR19","doi-asserted-by":"publisher","first-page":"E3334","DOI":"10.1073\/pnas.1616467114","volume":"114","author":"ASL Caldwell","year":"2017","unstructured":"Caldwell, A. S. L. et al. Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome. Proc Natl Acad Sci USA 114, E3334\u2013e3343, https:\/\/doi.org\/10.1073\/pnas.1616467114 (2017).","journal-title":"Proc Natl Acad Sci USA"},{"key":"55436_CR20","doi-asserted-by":"publisher","first-page":"7129","DOI":"10.1073\/pnas.0308058101","volume":"101","author":"SD Sullivan","year":"2004","unstructured":"Sullivan, S. D. & Moenter, S. M. Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: Implications for a common fertility disorder. Proceedings of the National Academy of Sciences of the United States of America 101, 7129\u20137134, https:\/\/doi.org\/10.1073\/pnas.0308058101 (2004).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"55436_CR21","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1210\/en.2010-0823","volume":"152","author":"AV Roland","year":"2011","unstructured":"Roland, A. V. & Moenter, S. M. Prenatal Androgenization of Female Mice Programs an Increase in Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons That Is Reversed by Metformin Treatment in Adulthood. Endocrinology 152, 618\u2013628, https:\/\/doi.org\/10.1210\/en.2010-0823 (2011).","journal-title":"Endocrinology"},{"key":"55436_CR22","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1210\/en.2012-1954","volume":"154","author":"AM Moore","year":"2013","unstructured":"Moore, A. M., Prescott, M. & Campbell, R. E. Estradiol Negative and Positive Feedback in a Prenatal Androgen-Induced Mouse Model of Polycystic Ovarian Syndrome. Endocrinology 154, 796\u2013806, https:\/\/doi.org\/10.1210\/en.2012-1954 (2013).","journal-title":"Endocrinology"},{"key":"55436_CR23","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1073\/pnas.1415038112","volume":"112","author":"AM Moore","year":"2015","unstructured":"Moore, A. M., Prescott, M., Marshall, C. J., Yip, S. H. & Campbell, R. E. Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome. Proceedings of the National Academy of Sciences 112, 596\u2013601, https:\/\/doi.org\/10.1073\/pnas.1415038112 (2015).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"55436_CR24","doi-asserted-by":"publisher","first-page":"e99405","DOI":"10.1172\/jci.insight.99405","volume":"3","author":"MS Silva","year":"2018","unstructured":"Silva, M. S., Prescott, M. & Campbell, R. E. Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS. Journal of clinical investigation insight 3, e99405, https:\/\/doi.org\/10.1172\/jci.insight.99405 (2018).","journal-title":"Journal of clinical investigation insight"},{"key":"55436_CR25","doi-asserted-by":"publisher","first-page":"3318","DOI":"10.1210\/jc.2008-0255","volume":"93","author":"SE Recabarren","year":"2008","unstructured":"Recabarren, S. E. et al. Pituitary and testicular function in sons of women with polycystic ovary syndrome from infancy to adulthood. The Journal of clinical endocrinology and metabolism 93, 3318\u20133324, https:\/\/doi.org\/10.1210\/jc.2008-0255 (2008).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"55436_CR26","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.fertnstert.2016.03.029","volume":"106","author":"LC Torchen","year":"2016","unstructured":"Torchen, L. C. et al. Increased antimullerian hormone levels and other reproductive endocrine changes in adult male relatives of women with polycystic ovary syndrome. Fertility and sterility 106, 50\u201355, https:\/\/doi.org\/10.1016\/j.fertnstert.2016.03.029 (2016).","journal-title":"Fertility and sterility"},{"key":"55436_CR27","doi-asserted-by":"publisher","first-page":"6218","DOI":"10.1210\/jc.2004-0918","volume":"89","author":"CM Bruns","year":"2004","unstructured":"Bruns, C. M. et al. Insulin resistance and impaired insulin secretion in prenatally androgenized male rhesus monkeys. J Clin Endocrinol Metab 89, 6218\u20136223, https:\/\/doi.org\/10.1210\/jc.2004-0918 (2004).","journal-title":"J Clin Endocrinol Metab"},{"key":"55436_CR28","doi-asserted-by":"publisher","first-page":"6444","DOI":"10.1210\/en.2008-0785","volume":"149","author":"SE Recabarren","year":"2008","unstructured":"Recabarren, S. E. et al. Prenatal testosterone excess reduces sperm count and motility. Endocrinology 149, 6444\u20136448, https:\/\/doi.org\/10.1210\/en.2008-0785 (2008).","journal-title":"Endocrinology"},{"key":"55436_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1530\/REP-10-0210","volume":"142","author":"CL Bormann","year":"2011","unstructured":"Bormann, C. L., Smith, G. D., Padmanabhan, V. & Lee, T. M. Prenatal testosterone and dihydrotestosterone exposure disrupts ovine testicular development. Reproduction 142, 167\u2013173, https:\/\/doi.org\/10.1530\/REP-10-0210 (2011).","journal-title":"Reproduction"},{"key":"55436_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.domaniend.2017.07.001","volume":"62","author":"CM Scully","year":"2018","unstructured":"Scully, C. M. et al. Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior. Domestic animal endocrinology 62, 1\u20139, https:\/\/doi.org\/10.1016\/j.domaniend.2017.07.001 (2018).","journal-title":"Domestic animal endocrinology"},{"key":"55436_CR31","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.domaniend.2017.06.004","volume":"61","author":"SE Recabarren","year":"2017","unstructured":"Recabarren, S. E. et al. Puberty arises with testicular alterations and defective AMH expression in rams prenatally exposed to testosterone. Domestic animal endocrinology 61, 100\u2013107, https:\/\/doi.org\/10.1016\/j.domaniend.2017.06.004 (2017).","journal-title":"Domestic animal endocrinology"},{"key":"55436_CR32","doi-asserted-by":"publisher","first-page":"E998","DOI":"10.1152\/ajpendo.00032.2010","volume":"299","author":"PP Rojas-Garcia","year":"2010","unstructured":"Rojas-Garcia, P. P. et al. Prenatal testosterone excess alters Sertoli and germ cell number and testicular FSH receptor expression in rams. American journal of physiology. Endocrinology and metabolism 299, E998\u2013e1005, https:\/\/doi.org\/10.1152\/ajpendo.00032.2010 (2010).","journal-title":"American journal of physiology. Endocrinology and metabolism"},{"key":"55436_CR33","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1530\/rep-13-0006","volume":"145","author":"MP Recabarren","year":"2013","unstructured":"Recabarren, M. P. et al. Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development. Reproduction (Cambridge, England) 145, 567\u2013576, https:\/\/doi.org\/10.1530\/rep-13-0006 (2013).","journal-title":"Reproduction (Cambridge, England)"},{"key":"55436_CR34","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.physbeh.2017.10.030","volume":"187","author":"MM McCarthy","year":"2018","unstructured":"McCarthy, M. M., Herold, K. & Stockman, S. L. Fast, furious and enduring: Sensitive versus critical periods in sexual differentiation of the brain. Physiol Behav 187, 13\u201319, https:\/\/doi.org\/10.1016\/j.physbeh.2017.10.030 (2018).","journal-title":"Physiol Behav"},{"key":"55436_CR35","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1210\/en.2018-01047","volume":"160","author":"SY Han","year":"2019","unstructured":"Han, S. Y., Kane, G., Cheong, I. & Herbison, A. E. Characterization of GnRH Pulse Generator Activity in Male Mice Using GCaMP Fiber Photometry. Endocrinology 160, 557\u2013567, https:\/\/doi.org\/10.1210\/en.2018-01047 (2019).","journal-title":"Endocrinology"},{"key":"55436_CR36","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.neuron.2006.07.023","volume":"52","author":"TM Wintermantel","year":"2006","unstructured":"Wintermantel, T. M. et al. Definition of Estrogen Receptor Pathway Critical for Estrogen Positive Feedback to Gonadotropin-Releasing Hormone Neurons and Fertility. Neuron 52, 271\u2013280, https:\/\/doi.org\/10.1016\/j.neuron.2006.07.023 (2006).","journal-title":"Neuron"},{"key":"55436_CR37","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1523\/jneurosci.19-06-02037.1999","volume":"19","author":"DJ Spergel","year":"1999","unstructured":"Spergel, D. J., Kr\u00fcth, U., Hanley, D. F., Sprengel, R. & Seeburg, P. H. GABA- and Glutamate-Activated Channels in Green Fluorescent Protein-Tagged Gonadotropin-Releasing Hormone Neurons in Transgenic Mice. The Journal of Neuroscience 19, 2037\u20132050, https:\/\/doi.org\/10.1523\/jneurosci.19-06-02037.1999 (1999).","journal-title":"The Journal of Neuroscience"},{"key":"55436_CR38","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1523\/JNEUROSCI.2304-17.2018","volume":"38","author":"T Berg","year":"2018","unstructured":"Berg, T., Silveira, M. A. & Moenter, S. M. Prepubertal Development of GABAergic Transmission to Gonadotropin-Releasing Hormone (GnRH) Neurons and Postsynaptic Response Are Altered by Prenatal Androgenization. J Neurosci 38, 2283\u20132293, https:\/\/doi.org\/10.1523\/JNEUROSCI.2304-17.2018 (2018).","journal-title":"J Neurosci"},{"issue":"11","key":"55436_CR39","doi-asserted-by":"publisher","first-page":"3943","DOI":"10.1210\/en.2017-00768","volume":"158","author":"Eden A Dulka","year":"2017","unstructured":"Dulka, E. A. & Moenter, S. M. Prepubertal development of gonadotropin-releasing hormone (GnRH) neuron activity is altered by sex, age and prenatal androgen exposure. Endocrinology, https:\/\/doi.org\/10.1210\/en.2017-00768 (2017).","journal-title":"Endocrinology"},{"key":"55436_CR40","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1677\/JOE-10-0217","volume":"207","author":"AV Roland","year":"2010","unstructured":"Roland, A. V., Nunemaker, C. S., Keller, S. R. & Moenter, S. M. Prenatal androgen exposure programs metabolic dysfunction in female mice. J Endocrinol 207, 213\u2013223, https:\/\/doi.org\/10.1677\/JOE-10-0217 (2010).","journal-title":"J Endocrinol"},{"key":"55436_CR41","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz180","author":"M Manti","year":"2019","unstructured":"Manti, M. et al. Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring. Cardiovasc Res. https:\/\/doi.org\/10.1093\/cvr\/cvz180 (2019).","journal-title":"Cardiovasc Res"},{"key":"55436_CR42","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/j.1365-2605.2011.01236.x","volume":"35","author":"A Dean","year":"2012","unstructured":"Dean, A., Smith, L. B., Macpherson, S. & Sharpe, R. M. The effect of dihydrotestosterone exposure during or prior to the masculinization programming window on reproductive development in male and female rats. Int J Androl 35, 330\u2013339, https:\/\/doi.org\/10.1111\/j.1365-2605.2011.01236.x (2012).","journal-title":"Int J Androl"},{"key":"55436_CR43","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1095\/biolreprod61.3.599","volume":"61","author":"S-J Kim","year":"1999","unstructured":"Kim, S.-J., Wood, R. I. & Foster, D. L. Prenatal Testosterone Masculinizes Synaptic Input to Gonadotropin-Releasing Hormone Neurons in Sheep. Biology of Reproduction 61, 599\u2013605, https:\/\/doi.org\/10.1095\/biolreprod61.3.599 (1999).","journal-title":"Biology of Reproduction"},{"key":"55436_CR44","doi-asserted-by":"publisher","first-page":"E257","DOI":"10.1152\/ajpendo.1982.243.3.E257","volume":"243","author":"A Coquelin","year":"1982","unstructured":"Coquelin, A. & Desjardins, C. Luteinizing hormone and testosterone secretion in young and old male mice. American Journal of Physiology-Endocrinology and Metabolism 243, E257\u2013E263, https:\/\/doi.org\/10.1152\/ajpendo.1982.243.3.E257 (1982).","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"55436_CR45","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1210\/endo-111-6-2055","volume":"111","author":"RA Steiner","year":"1982","unstructured":"Steiner, R. A., Bremner, W. J. & Clifton, D. K. Regulation of luteinizing hormone pulse frequency and amplitude by testosterone in the adult male rat. Endocrinology 111, 2055\u20132061, https:\/\/doi.org\/10.1210\/endo-111-6-2055 (1982).","journal-title":"Endocrinology"},{"key":"55436_CR46","doi-asserted-by":"publisher","first-page":"E658","DOI":"10.1152\/ajpendo.1988.254.5.E658","volume":"254","author":"DI Spratt","year":"1988","unstructured":"Spratt, D. I. et al. Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone. American Journal of Physiology-Endocrinology and Metabolism 254, E658\u2013E666, https:\/\/doi.org\/10.1152\/ajpendo.1988.254.5.E658 (1988).","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"55436_CR47","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1095\/biolreprod.107.066126","volume":"79","author":"J Ehmcke","year":"2008","unstructured":"Ehmcke, J., Ramaswamy, S., Schlatt, S. & Pohl, C. R. Age-Related Changes in Diurnal Rhythms and Levels of Gonadotropins, Testosterone, and Inhibin B in Male Rhesus Monkeys (Macaca mulatta)1. Biology of Reproduction 79, 93\u201399, https:\/\/doi.org\/10.1095\/biolreprod.107.066126 (2008).","journal-title":"Biology of Reproduction"},{"key":"55436_CR48","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/j.1365-2605.2004.00502.x","volume":"27","author":"RW Holdcraft","year":"2004","unstructured":"Holdcraft, R. W. & Braun, R. E. Hormonal regulation of spermatogenesis. International journal of andrology 27, 335\u2013342, https:\/\/doi.org\/10.1111\/j.1365-2605.2004.00502.x (2004).","journal-title":"International journal of andrology"},{"key":"55436_CR49","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1530\/EC-17-0218","volume":"6","author":"N Crisosto","year":"2017","unstructured":"Crisosto, N. et al. Reproductive and metabolic features during puberty in sons of women with polycystic ovary syndrome. Endocr Connect 6, 607\u2013613, https:\/\/doi.org\/10.1530\/EC-17-0218 (2017).","journal-title":"Endocr Connect"},{"key":"55436_CR50","doi-asserted-by":"publisher","first-page":"3639","DOI":"10.1210\/jc.2012-1761","volume":"97","author":"F Tuttelmann","year":"2012","unstructured":"Tuttelmann, F. et al. Combined effects of the variants FSHB-211G>T and FSHR 2039A>G on male reproductive parameters. The Journal of clinical endocrinology and metabolism 97, 3639\u20133647, https:\/\/doi.org\/10.1210\/jc.2012-1761 (2012).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"55436_CR51","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.reprotox.2012.12.005","volume":"36","author":"ZO Kyjovska","year":"2013","unstructured":"Kyjovska, Z. O. et al. Daily sperm production: Application in studies of prenatal exposure to nanoparticles in mice. Reproductive Toxicology 36, 88\u201397, https:\/\/doi.org\/10.1016\/j.reprotox.2012.12.005 (2013).","journal-title":"Reproductive Toxicology"},{"key":"55436_CR52","first-page":"3","volume":"37","author":"RA Davey","year":"2016","unstructured":"Davey, R. A. & Grossmann, M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. The Clinical biochemist. Reviews 37, 3\u201315 (2016).","journal-title":"The Clinical biochemist. Reviews"},{"key":"55436_CR53","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1210\/endo.139.4.5863","volume":"139","author":"SF Lu","year":"1998","unstructured":"Lu, S. F., McKenna, S. E., Cologer-Clifford, A., Nau, E. A. & Simon, N. G. Androgen receptor in mouse brain: sex differences and similarities in autoregulation. Endocrinology 139, 1594\u20131601, https:\/\/doi.org\/10.1210\/endo.139.4.5863 (1998).","journal-title":"Endocrinology"},{"key":"55436_CR54","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.neurobiolaging.2003.10.011","volume":"25","author":"RC Kumar","year":"2004","unstructured":"Kumar, R. C. & Thakur, M. K. Androgen receptor mRNA is inversely regulated by testosterone and estradiol in adult mouse brain. Neurobiology of aging 25, 925\u2013933, https:\/\/doi.org\/10.1016\/j.neurobiolaging.2003.10.011 (2004).","journal-title":"Neurobiology of aging"},{"key":"55436_CR55","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/39908","volume":"389","author":"SL McIntire","year":"1997","unstructured":"McIntire, S. L., Reimer, R. J., Schuske, K., Edwards, R. H. & Jorgensen, E. M. Identification and characterization of the vesicular GABA transporter. Nature 389, 870\u2013876, https:\/\/doi.org\/10.1038\/39908 (1997).","journal-title":"Nature"},{"key":"55436_CR56","doi-asserted-by":"publisher","first-page":"e12657","DOI":"10.1111\/jne.12657","volume":"30","author":"AM Moore","year":"2018","unstructured":"Moore, A. M., Abbott, G., Mair, J., Prescott, M. & Campbell, R. E. Mapping GABA and glutamate inputs to gonadotrophin-releasing hormone neurones in male and female mice. J Neuroendocrinol 30, e12657, https:\/\/doi.org\/10.1111\/jne.12657 (2018).","journal-title":"J Neuroendocrinol"},{"key":"55436_CR57","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.1210\/en.2017-00285","volume":"158","author":"MJ Kreisman","year":"2017","unstructured":"Kreisman, M. J. et al. Androgens Mediate Sex-Dependent Gonadotropin Expression During Late Prenatal Development in the Mouse. Endocrinology 158, 2884\u20132894, https:\/\/doi.org\/10.1210\/en.2017-00285 (2017).","journal-title":"Endocrinology"},{"key":"55436_CR58","doi-asserted-by":"publisher","first-page":"4234","DOI":"10.1210\/en.2016-1411","volume":"157","author":"CE Roselli","year":"2016","unstructured":"Roselli, C. E. et al. Excess Testosterone Exposure Alters Hypothalamic-Pituitary-Testicular Axis Dynamics and Gene Expression in Sheep Fetuses. Endocrinology 157, 4234\u20134245, https:\/\/doi.org\/10.1210\/en.2016-1411 (2016).","journal-title":"Endocrinology"},{"key":"55436_CR59","doi-asserted-by":"publisher","first-page":"4939","DOI":"10.1210\/en.2013-1502","volume":"154","author":"FJ Steyn","year":"2013","unstructured":"Steyn, F. J. et al. Development of a Methodology for and Assessment of Pulsatile Luteinizing Hormone Secretion in Juvenile and Adult Male Mice. Endocrinology 154, 4939\u20134945, https:\/\/doi.org\/10.1210\/en.2013-1502 (2013).","journal-title":"Endocrinology"},{"key":"55436_CR60","doi-asserted-by":"publisher","first-page":"E10216","DOI":"10.1073\/pnas.1713897114","volume":"114","author":"J Clarkson","year":"2017","unstructured":"Clarkson, J. et al. Definition of the hypothalamic GnRH pulse generator in mice. Proceedings of the National Academy of Sciences 114, E10216\u2013E10223, https:\/\/doi.org\/10.1073\/pnas.1713897114 (2017).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"55436_CR61","doi-asserted-by":"publisher","first-page":"e39001","DOI":"10.1371\/journal.pone.0039001","volume":"7","author":"A Vidal","year":"2012","unstructured":"Vidal, A., Zhang, Q., M\u00e9digue, C., Fabre, S. & Cl\u00e9ment, F. DynPeak: An Algorithm for Pulse Detection and Frequency Analysis in Hormonal Time Series. PLoS One 7, e39001, https:\/\/doi.org\/10.1371\/journal.pone.0039001 (2012).","journal-title":"PLoS One"},{"unstructured":"Franklin, K. B. J. & Paxinos, G. The mouse brain in stereotaxic coordinates. 3rd ed. edn, (Elsevier\/Academic Press, 2008).","key":"55436_CR62"},{"key":"55436_CR63","doi-asserted-by":"publisher","first-page":"3200","DOI":"10.1210\/en.2018-00505","volume":"159","author":"AM Moore","year":"2018","unstructured":"Moore, A. M. et al. Synaptic Innervation of the GnRH Neuron Distal Dendron in Female Mice. Endocrinology 159, 3200\u20133208, https:\/\/doi.org\/10.1210\/en.2018-00505 (2018).","journal-title":"Endocrinology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55436-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55436-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55436-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T17:24:05Z","timestamp":1671297845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-55436-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,11]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["55436"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-55436-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2019,12,11]]},"assertion":[{"value":"14 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18908"}}