New knowledge on reproductive biology

Professor Susana M. Chuva de Sousa Lopes

Research in the lab of Professor Susana Chuva de Sousa Lopes (reNEW Leiden) has resulted in three publications. Two research papers, published in Developmental Cell and Cell Reports Medicine, present new knowledge on human reproduction and developmental biology of the reproductive organs. In addition, a protocol published in Methods in Molecular Biology provides guidelines to study cells of the human fetal testis.

Ovulation in transmasculine people
The first paper, published in Cell Reports Medicine focuses on ovulation in transmasculine individuals. Transmasculine individuals are born female but don’t identify as such and therefore frequently undergo a hormone treatment with testosterone to masculinize physically. As a consequence, these individuals typically stop menstruating. In collaboration with researchers from the Amsterdam UMC, Chuva de Sousa Lopes and her team examined ovarian tissues of transmasculine individuals taking testosterone. Doing so, they made the surprising discovery that one third of these individuals recently ovulated. Julieta del Valle, PhD student in the lab of Chuva de Sousa Lopes: “The surprising results from this study have strong implications for sexually active transmasculine individuals as it shows they are at risk of pregnancy even though they do not menstruate anymore. To avoid unwanted pregnancy, it is hence necessary to use contraceptives.”

A developmental roadmap of the human gonad and reproductive tract
In the second paper, published in and featured on the cover of Developmental Cell, the team performed single-cell transcriptomics to characterize development of both male and female human fetal gonads (ovary and testis) and the adjacently developing reproductive tracts over time. “Single-cell transcriptomics allowed us to validate different cell populations present during development of both male and female reproductive organs,” explains Jasin Taelman, co-first author on the paper. Especially development of the reproductive tract had thus far been understudied. The results presented in the new paper reveal novel insights into this process. Sylwia Czuskiewska, other co-first author of the paper: “Using our datasets, we now observed that pronounced sex differences emerge in the reproductive tract as early as the first trimester. Interestingly, key genes during this development associate with urogenital diseases. This suggests sex-specific involvement of these genes in diseases.” The published single-cell datasets thus provide a valuable resource to obtain novel insights into sex differentiation of the gonads and surrounding tissues during development. In addition, the datasets could contribute to improved knowledge on the causes of urogenital disease and identification of novel treatments.

A protocol for the study of cells from human fetal testis
Fetal Germ Cells (FGCs) in human fetal testis are the predecessors of spermatogonia: the sperm producing celltype in our body. “Although FGCs in the first and second trimester of development have been well characterized with transcriptomic approaches, FGCs in the second trimester transition between two cell states in a heterogeneous manner,“ explains Celine Roelse, a PhD student from the Chuva de Sousa Lopes lab. As a result, little is known about development of FGCs during this window. She continues: “The lack of knowledge on this transition has hampered progress in production and long-term culture of sperm in the lab. Hence there’s a need for in vitro culture system in which we can study the mechanisms that support this transition”. Chuva Sousa de Lopes and her team now published such a protocol for the isolation and in vitro culture of cells from the human fetal testis in the book Germ Cell Development (part of the series Methods in Molecular Biology). “The protocol opens new possibilities to study this transition. Future studies based on this protocol can provide crucial knowledge for the development of methods for male fertility preservation and the identification of causes and therapies for male infertility,” concludes Chuva de Sousa Lopes.

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