Manuel Tena-Sempere

Manuel Tena-Sempere

Professor of Physiology

Senior Research Associate



ORCID ID: 0000-0002-4741-5567

Description of Research

Our research group is interested in deciphering the neuroendocrine and molecular mechanisms responsible for the control of puberty and reproductive function, and how these finely interplay with the systems governing body weight and metabolic homeostasis. In this context, we are actively working in the characterization of the role of different neuropeptide systems in the neurohormonal regulation of puberty onset and fertility, with special attention to the analysis of the functions of kisspeptins and their interactions with other central (e.g., neurokinin B, other tachykinins, melanocortins, GnIH) and peripheral (e.g., leptin, sex steroids) regulators, as well as modulation by nutritional and metabolic cues. More recently, our group has become interested in disclosing the role of novel regulatory mechanisms, such as miRNAs, epigenetics and cellular energy sensors, in the joint control of metabolism and reproduction, and how these interplay with central neuropeptide networks (specially kisspeptins). This basic knowledge, generated mostly by the use of at-the-edge preclinical (rodent) models and techniques in neuroendocrine research has set the basis for implementation of translational projects, currently running in our group, targeting the metabolic and reproductive consequences of obesity-induced hypogonadism, as well as improved strategies for the diagnosis and treatment of common reproductive disorders, such as polycystic ovarian syndrome.

Current Topics

  • To define the roles of miRNAs, cellular energy sensors and epigenetics in the control of key neuronal populations of the reproductive brain, such as Kiss1 neurons
  • To address the roles of Kiss1 neurons, and related neuronal populations, in the control of puberty and fertility, and their modulation by metabolic factors
  • To characterize the mechanisms and impact of hormonal and metabolic alterations linked to obesity, with special attention to obesity-induced hypogonadism
  • To determine the translational value of different neuroendocrine signals and pathways for the improvement of etiopathogenic, diagnostic and therapeutic management of common metabolic and reproductive disorders, such as obesity, infertility and polycystic ovarian syndrome.

Representative Publications:

Connecting nutritional deprivation and pubertal inhibition via GRK2-mediated repression of kisspeptin actions in GnRH neurons.  Perdices-Lopez C, Avendaño MS, Barroso A, Gaytán F, Ruiz-Pino F, Vázquez MJ, Leon S, Song YB, Sobrino V, Heras V, Romero-Ruiz A, Roa J, Mayor F Jr, Murga C, Pinilla L, Kaiser UB, Tena-Sempere M. Metabolism. 2022 Apr;129:155141. doi: 10.1016/j.metabol.2022.155141. Epub 2022 Jan 22. PMID: 35074314

Central Ceramide Signaling Mediates Obesity-Induced Precocious Puberty.  Heras V, Castellano JM, Fernandois D, Velasco I, Rodríguez-Vazquez E, Roa J, Vazquez MJ, Ruiz-Pino F, Rubio M, Pineda R, Torres E, Avendaño MS, Paredes A, Pinilla L, Belsham D, Diéguez C, Gaytán F, Casals N, López M, Tena-Sempere M. Cell Metab. 2020 Dec 1;32(6):951-966.e8. doi: 10.1016/j.cmet.2020.10.001. Epub 2020 Oct 19. PMID: 33080217

Role of kisspeptins in the control of the hypothalamic-pituitary-ovarian axis: old dogmas and new challenges.  Ruohonen ST, Poutanen M, Tena-Sempere M. Fertil Steril. 2020 Sep;114(3):465-474. doi: 10.1016/j.fertnstert.2020.06.038. Epub 2020 Aug 6. PMID: 32771258 Review.

Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis. Velasco I, León S, Barroso A, Ruiz-Pino F, Heras V, Torres E, León M, Ruohonen ST, García-Galiano D, Romero-Ruiz A, Sánchez-Garrido MA, Olhsson C, Castellano JM, Roa J, Poutanen M, Pinilla L, Vázquez MJ, Tena-Sempere M. Metabolism. 2019 Sep;98:84-94. doi: 10.1016/j.metabol.2019.06.007. Epub 2019 Jun 19. PMID: 31226351

Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling. Roa J, Barroso A, Ruiz-Pino F, Vázquez MJ, Seoane-Collazo P, Martínez-Sanchez N, García-Galiano D, Ilhan T, Pineda R, León S, Manfredi-Lozano M, Heras V, Poutanen M, Castellano JM, Gaytan F, Diéguez C, Pinilla L, López M, Tena-Sempere M. Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):E10758-E10767. doi: 10.1073/pnas.1802053115. Epub 2018 Oct 22. PMID: 30348767 Free PMC article.

SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression. Vazquez MJ, Toro CA, Castellano JM, Ruiz-Pino F, Roa J, Beiroa D, Heras V, Velasco I, Dieguez C, Pinilla L, Gaytan F, Nogueiras R, Bosch MA, Rønnekleiv OK, Lomniczi A, Ojeda SR, Tena-Sempere M. Nat Commun. 2018 Oct 10;9(1):4194. doi: 10.1038/s41467-018-06459-9. PMID: 30305620 Free PMC article.

Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure. Ruohonen ST, Gaytan F, Usseglio Gaudi A, Velasco I, Kukoricza K, Perdices-Lopez C, Franssen D, Guler I, Mehmood A, Elo LL, Ohlsson C, Poutanen M, Tena-Sempere M. Hum Reprod. 2022 Jan 17:deab287. doi: 10.1093/humrep/deab287. Online ahead of print. PMID: 35037941

Congenital ablation of Tacr2 reveals overlapping and redundant roles of NK2R signaling in the control of reproductive axis. Torres E, Velasco I, Franssen D, Heras V, Gaytan F, Leon S, Navarro VM, Pineda R, Candenas ML, Romero-Ruiz A, Tena-Sempere M. Am J Physiol Endocrinol Metab. 2021 Mar 1;320(3):E496-E511. doi: 10.1152/ajpendo.00346.2020. Epub 2021 Jan 11. PMID: 33427049 Free PMC article.

Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome. Romero-Ruiz A, Skorupskaite K, Gaytan F, Torres E, Perdices-Lopez C, Mannaerts BM, Qi S, Leon S, Manfredi-Lozano M, Lopez-Rodriguez C, Avendaño MS, Sanchez-Garrido MA, Vazquez MJ, Pinilla L, van Duin M, Kohout TA, Anderson RA, Tena-Sempere M. Hum Reprod. 2019 Dec 1;34(12):2495-2512. doi: 10.1093/humrep/dez205. PMID: 31820802 Free PMC article. Clinical Trial.