Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
Magdalena Kurek,
Elisabet Åkesson,
Masahito Yoshihara,
Elizabeth Oliver,
Yanhua Cui,
Martin Becker,
João Pedro Alves-Lopes,
Ragnar Bjarnason,
Patrik Romerius,
Mikael Sundin,
Ulrika Norén Nyström,
Cecilia Langenskiöld,
Hartmut Vogt,
Lars Henningsohn,
Cecilia Petersen,
Olle Söder,
Jingtao Guo,
Rod T. Mitchell,
Kirsi Jahnukainen,
Jan-Bernd Stukenborg
Affiliations
Magdalena Kurek
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Elisabet Åkesson
Division of Neurogeriatrics, Department of Neurobiology Care Sciences & Society, Karolinska Institutet, 141 83 Huddinge, Sweden
Masahito Yoshihara
Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden
Elizabeth Oliver
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Yanhua Cui
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Martin Becker
Center of Neurodevelopmental Disorders (KIND), Department of Women’s and Children’s Health, Karolinska Institutet, Centre for Psychiatry Research, Region Stockholm and Astrid Lindgren Children’s Hospital, Karolinska University Hospital, 171 64 Solna, Sweden
João Pedro Alves-Lopes
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Ragnar Bjarnason
Children’s Medical Center, Landspítali University Hospital, 101 Reykjavik, Iceland
Patrik Romerius
Department of Paediatric Oncology and Haematology, Clinical Sciences, Lund University, Barn-och Ungdomssjukhuset Lund, Skånes Universitetssjukhus, 221 85 Lund, Sweden
Mikael Sundin
Division of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 52 Huddinge, Sweden
Ulrika Norén Nyström
Division of Paediatrics, Department of Clinical Science, Umeå University, 901 87 Umeå, Sweden
Cecilia Langenskiöld
Department of Paediatric Oncology, The Queen Silvia Children’s Hospital, 416 50 Gothenburg, Sweden
Hartmut Vogt
Crown Princess Victoria’s Child and Youth Hospital, and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden
Lars Henningsohn
Division of Urology, Institution for Clinical Science Intervention and Technology, Karolinska Institutet, 141 52 Huddinge, Sweden
Cecilia Petersen
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Olle Söder
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Jingtao Guo
Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Rod T. Mitchell
MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK
Kirsi Jahnukainen
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Jan-Bernd Stukenborg
NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Karolinska University Hospital, 171 64 Solna, Sweden
Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
