The early determinants of reproductive health

Description of Research

Reproductive health is based on normal fetal and childhood development. However, it has been difficult to demonstrate a direct link between adult reproductive health problems and early devel-opment in human because there have not been long-term studies from pregnancy to adulthood. Now we are performing a comprehensive reproductive health study for 19-year-old men that we have followed up prospectively from pregnancy through mini-puberty (three months from birth) collecting genetic and questionnaire data, placentas, breast milk, blood samples, and measuring their gonadal growth in 1997-1999. Their reproductive hormones were measured, and more than 100 environmental toxicants were measured in breast milk and placentas. Subgroups of boys were followed up to 18 months and again from 8.5 years through puberty. Now we examine their adult reproductive health by measuring their gonadal size, reproductive hormones and semen quality to analyze how the early life findings correlate with the adult outcome, and how the genetic background, chemical exposures and lifestyle factors might influence it. The number of Sertoli cells in the testis dictates sperm production capacity. We have shown that Sertoli cell proliferation is regulated by retinoblastoma protein (Rb) and E2F3 transcription factor. We are studying the role of different Rb family proteins and their interacting E2F transcription factors in gonadal development. Adverse trends in reproductive health have raised a concern whether endocrine disruptors cause these problems. We are investigating this both in the cohort study and in in vitro experiments where we test the effects of endocrine disruptors in rat fetal testis organ cultures and in seminiferous tubule cultures. These model systems are also used to explore the adverse effects of novel cancer drugs. The aim is to identify risk factors of reproductive health to make their management possible, and ultimately mitigate hazards and prevent reproductive health problems.

List of Personnel

Helena Virtanen, MD, PhD, Docent
Mirja Nurmio, PhD
Wiwat Rodprasert, MD
Emmi Rotgers, MD
Sergey Sadov, MD
Sheyla Cisneros Montalvo, MSc
Jaakko Koskenniemi, BMed
Anna Eggert, BMed
Johanna Järvi, lab technician

Selected Publications

Mäkelä J-A, Saario V, Bourguiba-Hachemi S, Nurmio M, Jahnukainen K, Parvinen M, Toppari J: Hedgehog signalling promotes germ cell survival in the rat testis. Reproduction 142: 711-721, 2011.

Ventelä S, Mäkelä J-A, Kulmala J, Westermarck J, Toppari J: Identification and regulation of a stage-specific stem cell niche enriched by Nanog positive spermatogonial stem cells in the mouse testis. Stem Cells 30: 1008-20, 2012.

Perheentupa A, Mäkinen J, Laatikainen T, Vierula M, Skakkebaek N, Andersson AM, Toppari J: A Cohort Effect on Serum Testosterone Levels in Finnish Men. Eur J Endocrinol. 168: 227-33, 2013.

Rotgers E, Rivero-Müller A, Nurmio M, Parvinen M, Guillou F, Huhtaniemi I, Kotaja, Bourguiba-Hachemi S, Toppari J. Retinoblastomaprotein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells. Cell Death and Disease 5:e1274. doi: 10.1038/cddis.2014.232.

Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT. The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev. 2015 Dec;36(6):E1-E150.