TY - JOUR
T1 - iPSCs derived from infertile men carrying complex genetic abnormalities can generate primordial germ-like cells
AU - Mouka, Aurélie
AU - Arkoun, Brahim
AU - Moison, Pauline
AU - Drévillon, Loïc
AU - Jarray, Rafika
AU - Brisset, Sophie
AU - Mayeur, Anne
AU - Bouligand, Jérôme
AU - Boland-Auge, Anne
AU - Deleuze, Jean François
AU - Yates, Frank
AU - Lemonnier, Thomas
AU - Callier, Patrick
AU - Duffourd, Yannis
AU - Nitschke, Patrick
AU - Ollivier, Emmanuelle
AU - Bourdin, Arnaud
AU - De Vos, John
AU - Livera, Gabriel
AU - Tachdjian, Gérard
AU - Maouche-Chrétien, Leïla
AU - Tosca, Lucie
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Despite increasing insight into the genetics of infertility, the developmental disease processes remain unclear due to the lack of adequate experimental models. The advent of induced pluripotent stem cell (iPSC) technology has provided a unique tool for in vitro disease modeling enabling major advances in our understanding of developmental disease processes. We report the full characterization of complex genetic abnormalities in two infertile patients with either azoospermia or XX male syndrome and we identify genes of potential interest implicated in their infertility. Using the erythroblasts of both patients, we generated primed iPSCs and converted them into a naive-like pluripotent state. Naive-iPSCs were then differentiated into primordial germ-like cells (PGC-LCs). The expression of early PGC marker genes SOX17, CD-38, NANOS3, c-KIT, TFAP2C, and D2-40, confirmed progression towards the early germline stage. Our results demonstrate that iPSCs from two infertile patients with significant genetic abnormalities are capable of efficient production of PGCs. Such in vitro model of infertility will certainly help identifying causative factors leading to early germ cells development failure and provide a valuable tool to explore novel therapeutic strategies.
AB - Despite increasing insight into the genetics of infertility, the developmental disease processes remain unclear due to the lack of adequate experimental models. The advent of induced pluripotent stem cell (iPSC) technology has provided a unique tool for in vitro disease modeling enabling major advances in our understanding of developmental disease processes. We report the full characterization of complex genetic abnormalities in two infertile patients with either azoospermia or XX male syndrome and we identify genes of potential interest implicated in their infertility. Using the erythroblasts of both patients, we generated primed iPSCs and converted them into a naive-like pluripotent state. Naive-iPSCs were then differentiated into primordial germ-like cells (PGC-LCs). The expression of early PGC marker genes SOX17, CD-38, NANOS3, c-KIT, TFAP2C, and D2-40, confirmed progression towards the early germline stage. Our results demonstrate that iPSCs from two infertile patients with significant genetic abnormalities are capable of efficient production of PGCs. Such in vitro model of infertility will certainly help identifying causative factors leading to early germ cells development failure and provide a valuable tool to explore novel therapeutic strategies.
UR - http://www.scopus.com/inward/record.url?scp=85136228389&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-17337-2
DO - 10.1038/s41598-022-17337-2
M3 - Article
C2 - 35995809
AN - SCOPUS:85136228389
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14302
ER -