NORDFERTIL Research and Publications

Survival rates among childhood cancer patients have progressively increased over the past four decades, in particular as a result of the development of more effective cancer treatments. Three out of four children will be cured of their disease. However, success has come at a cost and some patients will suffer from adverse effects later on. One of these late effects may be treatment-induced infertility.

Background

Boys who have matured into puberty are offered sperm preservation before treatment starts. However, for boys before puberty there is as yet no procedure that may preserve fertility. Most childhood cancer treatments will have only a minor impact on future fertility, while some treatments are known to be very harmful as regards reproductive function. So far, boys facing such treatments have almost no chance to father their own biological children later in life.

To address the concerns of many patients and parents and to open a forum concentrating on infertility as a disease, or a treatment-related late effect in childhood cancer survivors, the “Nordic Network for Gonadal Preservation after Cancer Treatment in Children and Young Adults” was initiated in 2008 and resulted in recommendations concerning fertility preservation for girls/boys and young women/men with childhood cancer. Up to now, advances in females have been made, but a similar development is still missing for young boys. Therefore, the idea of establishing a scientific network in order to intensify and combine research efforts on fertility preservation for young boys was born. The network is named NORDFERTIL.

The research of this network is centralized at the NORDFERTIL Research Lab Stockholm at Karolinska Institutet and includes research areas including pluripotent stem cell cultures as well as the development of novel in vitro systems for male gonadal cell development and differentiation.

In addition to the research performed, NORDFERTIL will focus on the establishment of protocols for clinical applications. Therefore, the results obtained by evaluation of testicular biopsy material and cell culture experiments will be used to generate and/or optimize already existing protocols for clinical use in cooperation with all units included in NORDFERTIL.

Photo: Jan-Bernd Stukenborg

The following questions will be addressed:

  1. Which are the best cryopreservation protocols as regards later differentiation of early male germ cells in vitro?
  2. Which are the best strategies to monitor cancer cell contamination in vitro?
  3. Which are the best strategies and culture conditions for human spermatogenesis in vitro?
  4. Which clinical efficacy and safety measures should be monitored?

Publications

Self-organising human gonads generated by a Matrigel-based gradient system.
Oliver E, Alves-Lopes JP, Harteveld F, Mitchell RT, Åkesson E, Söder O, Stukenborg JB
BMC Biol 2021 09;19(1):212Publication 

Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment.
Guo J, Sosa E, Chitiashvili T, Nie X, Rojas EJ, Oliver E, , Plath K, Hotaling JM, Stukenborg JB, Clark AT, Cairns BR
Cell Stem Cell 2021 04;28(4):764-778.e4

Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation.
Kurek M, Åkesson E, Yoshihara M, Oliver E, Cui Y, Becker M, Alves-Lopes JP, Bjarnason R, Romerius P, Sundin M, Norén Nyström U, Langenskiöld C, Vogt H, Henningsohn L, Petersen C, Söder O, Guo J, Mitchell RT, Jahnukainen K, Stukenborg JB
Cells 2021 01;10(2):

Z-scores for comparative analyses of spermatogonial numbers throughout human development.
Funke M, Yang Y, Lahtinen A, Benninghoven-Frey K, Kliesch S, Neuhaus N, Stukenborg JB, Jahnukainen K
Fertil Steril 2021 09;116(3):713-720

Hormone Production by Human First-Trimester Gonads in a Functional In Vitro System.
Albalushi H, Sahlin L, Åkesson E, Kurek M, Kjartansdóttir KR, Lindh R, Söder O, Rotstein E, Hovatta O, Stukenborg JB
Endocrinology 2019 01;160(1):133-142

Human induced pluripotent stem cells from two azoospermic patients with Klinefelter syndrome show similar X chromosome inactivation behavior to female pluripotent stem cells.
Panula S, Kurek M, Kumar P, Albalushi H, Padrell Sánchez S, Damdimopoulou P, Olofsson JI, Hovatta O, Lanner F, Stukenborg JB
Hum Reprod 2019 11;34(11):2297-2310

Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy.
Stukenborg JB, Alves-Lopes JP, Kurek M, Albalushi H, Reda A, Keros V, Töhönen V, Bjarnason R, Romerius P, Sundin M, Norén Nyström U, Langenskiöld C, Vogt H, Henningsohn L, Mitchell RT, Söder O, Petersen C, Jahnukainen K
Hum Reprod 2018 09;33(9):1677-1683

Testicular organoids: a new model to study the testicular microenvironment in vitro?
Alves-Lopes JP, Stukenborg JB
Hum Reprod Update 2018 Mar;24(2):176-191

Use of a three-layer gradient system of cells for rat testicular organoid generation.
Alves-Lopes JP, Söder O, Stukenborg JB
Nat Protoc 2018 02;13(2):248-259

Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents.
Poganitsch-Korhonen M, Masliukaite I, Nurmio M, Lähteenmäki P, van Wely M, van Pelt AMM, Jahnukainen K, Stukenborg JB
Leukemia 2017 06;31(6):1460-1463