Biology of Reproduction & Stem Cell

João Ramalho-Santos

PhD, Principal Investigator

This new group was derived from the Metabolic Control Group, since there was both an increase in critical mass, and a focus on research aspects that are not as related to Metabolic Control. These include how basic research on metabolism and aging may influence Assisted Reproduction (ART) at distinct levels, also with the recruitment of MDs that helped the group move into more translational/clinical research. With a key common focus on energy production and oxidative stress the lines of research include:

  • Characterization of the molecular basis of gamete quality, notably identifying pathways and protein signatures of functional human sperm to both attempt to understand unexplained male infertility and select the more functional cells for clinical use;
  • Understanding the effects of environmental factors (diet, age, conditions such as diabetes, and Endocrine Disruptors) on sperm function, and evaluating putative transgenerational effects;
  • Identifying the molecular mechanisms underlying oocyte aging with the goal of reverting metabolic based dysfunction in oocytes of aging females;
  • Identifying the metabolic pathways determining embryonic stem cell fate to improve embryo quality in Assisted Reproduction;
  • Studying re-vascularization of cryopreserved sections of ovarian tissue in model animals to improve transplantation success rates;
  • Setting up a service (unique to Portugal) were female patients that become infertile following oncological treatment can re-implant sections of previously cryopreserved tissue and recover fertility (first successful transplant in 2015);
  • Perform clinical-based studies related to patient treatment and follow-up in Assisted Reproduction, including questionnaire-based research, correlations with clinical data, systematic literature reviews and meta-analysis on different aspects related to group activity (ART success, Oncofertility);
  • Perform Science Communication activities and Outreach in the field, and evaluate their impact.

Group Members

Group Members

Group members are: João Ramalho-Santos (PhD, Group Leader), Adalberto Fernandes, Adriana Fontes, Alexandra Carvalho, Alexandre Pires, Anabela Marisa Azul (PhD), Ana Filipa Branco (PhD), Ana Ferreira, Ana Paula Sousa (PhD), Ana Sofia Pais, Andreia Silva, Bibiana Silva, Maria Inês Alfaiate, Maria Inês Sousa, Maria Moreira Soares, Mireia Alemany i Pagès, Paula Mota (PhD), Sandra Reis, Renata Tavares (PhD), Sandra Amaral (PhD), Sara Rebelo, Teresa Almeida Santos (MD, PhD).

Selected Publications

Perestrelo, T, Correia M, Ramalho-Santos J* & Wirtz D* *co-corresponding authors (2018) Metabolic and mechanical cues in pluripotent stem cell fate. Trends in Cell Biology 28(12):1014-1029. doi: 10.1016/j.tcb.2018.09.005.

Tavares RS, Escada-Rebelo S, Silva AF, Sousa MI, Ramalho-Santos J, Amaral S (2018) Antidiabetic therapies and male reproductive function: where do we stand? Reproduction 155:R13-R37. doi: 10.1530/REP-17-0390.

Correia M, Perestrelo T, Rodrigues AS, Ribeiro MF, Pereira SL, Sousa MI & Ramalho-Santos J (2017) Sirtuins in metabolism, stemness and differentiation. Biochim Biophys Acta, BBA- General Subjects 1861:3444-3455, 2017. doi: 10.1016/j.bbagen.2016.09.008.

Tavares RS, Escada-Rebelo S, Correia M & Ramalho-Santos J. (2016). The non-genomic effects of endocrine-disrupting chemicals on mammalian sperm. Reproduction 151:R1-R13. doi: 10.1530/REP-15-0355.

Portela JM, Tavares RS, Mota PC, Ramalho-Santos J, Amaral S. (2015) High glucose concentrations per se do not adversely affect human sperm function in vitro. Reproduction. 150(1):77-84. doi: 10.1530/REP-15-0100.

Rodrigues AS, Correia M, Gomes A, Pereira SL, Perestrelo T, Sousa MI, Ramalho-Santos J. (2015) Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency. PLoS One. 6;10(7):e0131663. doi: 10.1371/journal.pone.0131663.

Tavares RS, Amaral S, Paiva C, Baptista M, Ramalho-Santos J. (2015) In vitro exposure to the organochlorine p,p'-DDE affects functional human sperm parameters. Chemosphere. 120:443-6. doi: 10.1016/j.chemosphere.2014.08.075.

Varela Amaral S, Forte T, Ramalho-Santos J, Girão da Cruz MT. (2015) I Want More and Better Cells! - An Outreach Project about Stem Cells and Its Impact on the General Population. PLoS One. 10(7):e0133753. doi: 10.1371/journal.pone.0133753.

Amaral A, Paiva C, Attardo Parrinello C, Estanyol JM, Ballescà JL, Ramalho-Santos J, Oliva R. (2014) Identification of proteins involved in human sperm motility using high-throughput differential proteomics. J Proteome Res. 13(12):5670-84. doi: 10.1021/pr500652y.

Tavares RS, Silva AF, Lourenço B, Almeida-Santos T, Sousa AP, Ramalho-Santos J. (2013) Evaluation of human sperm chromatin status after selection using a modified Diff-Quik stain indicates embryo quality and pregnancy outcomes following in vitro fertilization. Andrology. 1(6):830-7. doi: 10.1111/j.2047-2927.2013.00127.x.

Selected Grants

STEM@REST: A novel pluripotency stem cell state and its promise in stem cell bioengineering. CENTRO (2018-2021). PI: João Ramalho-Santos.

INFERTILY2EXPLAIN: In search of novel biomarkers for unexplained human male infertility. CENTRO (2018-2021). PI: Sandra Amaral.

MERCK Oncofertility Project. MERCK (2016-2020). PI: João Ramalho-Santos.

HealthyAging2020. CENTRO2020 (2017-2020). PI: João Ramalho-Santos.

Testing of spermicidal formulations. INNOTHERA International (2014-2020). PI: João Ramalho-Santos.

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