Article
Cell Biology
Michael Curley, Annalucia Darbey, Liza O'Donnell, Karen R. Kilcoyne, Kirsten Wilson, Will Mungall, Diane Rebourcet, Jingtao Guo, Rod T. Mitchell, Lee B. Smith
Summary: The LIFR signaling pathway negatively regulates steroidogenic enzyme expression and testosterone biosynthesis in testicular Leydig cells, providing new insights into the intricate regulation of LC steroidogenic function.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Xiaowei Gu, Shu-Yun Li, Satoko Matsuyama, Tony DeFalco
Summary: Steroidogenesis is a crucial biological process for embryonic development, reproduction, and adult health. In addition to traditional glandular cells, immune cells also play a role in steroid hormone production. This review highlights the regulatory role of immune cells in steroidogenesis in the testis and extra-glandular locations, providing opportunities for new insights into hormone production.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zoheir B. Demmouche, Jacques J. Tremblay
Summary: Leydig cells produce testosterone, a hormone essential for male sex differentiation and spermatogenesis. LH stimulates testosterone production by activating various kinases and transcription factors through increasing cAMP levels. AMPK, activated by AMP, potently represses steroidogenesis. The study identifies global changes in protein and phosphoprotein levels during both the stimulatory and inhibitory phases of steroidogenesis, providing new insights into the finely tuned processes of adequate steroid hormone production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Luc J. Martin, Ha Tuyen Nguyen
Summary: Transcription factors of the bZIP class are crucial for gene regulation and function in testicular Leydig cells. Different bZIP members are regulated by various signaling pathways, including the cAMP/PKA pathway and endoplasmic reticulum stress. This review summarizes the influences of bZIP transcription factors on cell proliferation, steroidogenesis, and Leydig cell communication, and identifies unresolved questions regarding their mechanisms of action in gene regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marie France Bouchard, Julia Picard, Jacques J. Tremblay, Robert S. Viger
Summary: In the testis, Leydig cells produce steroid hormones that are needed for masculinization and spermatogenesis. The study focused on the validation of the regulatory sequences required for the gene expression of STAR in an endogenous context.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Kai Otsuka, Shin Matsubara, Akira Shiraishi, Natsumi Takei, Yui Satoh, Miho Terao, Shuji Takada, Tomoya Kotani, Honoo Satake, Atsushi P. Kimura
Summary: The newly discovered testis-specific lncRNA, Start, is involved in testicular steroid activation, and its knockout leads to reduced testosterone levels, affecting spermatogenesis, but does not show significant abnormalities in adult mice.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Annick N. Enangue Njembele, Zoheir B. Demmouche, Janice L. Bailey, Jacques J. Tremblay
Summary: This study found that an environmentally relevant mixture of organochlorine chemicals (OCs) disrupts steroidogenesis in Leydig cells by decreasing the levels of the STAR protein, which is involved in cholesterol transportation for steroid hormone synthesis. Additionally, the OC mixture affects other proteins involved in mitochondrial transport, lipid metabolism, and steroidogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Ha Tuyen Nguyen, Mustapha Najih, Luc J. Martin
Summary: Members of the AP-1 family of transcription factors play critical roles in the regulation of Leydig cell proliferation, steroidogenesis, and cell-to-cell communication, participating in the transcriptional regulation of genes important for Leydig cell function.
Article
Biochemistry & Molecular Biology
Massimo Venditti, Davide Arcaniolo, Marco De Sio, Sergio Minucci
Summary: This study evaluated the potential relationships between cytoskeleton-associated proteins DAAM1 and PREP in different testicular disorders, revealing varied protein levels and localization patterns in classic seminoma, Leydig cell tumor, and Sertoli cell-only syndrome. The results suggest perturbed cytoarchitecture in these disorders and indicate the potential of DAAM1 and PREP as new markers. Additionally, a specific nuclear localization of DAAM1 was found in Leydig cell tumor spermatogonia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Xiaoju Guan, Panpan Chen, Minpeng Ji, Xin Wen, Dan Chen, Xingyi Zhao, Fu Huang, Jiexia Wang, Jingjing Shao, Jiajia Xie, Xingxing Zhao, Fenfen Chen, Jing Tian, Han Lin, Barry R. Zirkin, Ping Duan, Zhijian Su, Haolin Chen
Summary: In adult testis, stem Leydig cells (SLCs) could be involved in the regeneration of adult Leydig cells (ALCs). The proliferation and differentiation of SLCs are separately regulated, as indicated by the observation that cells proliferating after ALC loss were not the ones forming ALCs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Dijana Z. Marinkovic, Marija L. J. Medar, Alisa P. Becin, Silvana A. Andric, Tatjana S. Kostic
Summary: The study found that constant light exposure negatively impacts the endocrine and energy capacity of Leydig cells in rats, leading to delayed reproductive development, with the effects most pronounced during puberty, including changes in hormone levels, mitochondrial function, and gene expression. In adults, the negative effects on mitochondrial function and steroidogenic capacity persisted in Leydig cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Xingyi Zhao, Minpeng Ji, Xin Wen, Dan Chen, Fu Huang, Xiaoju Guan, Jing Tian, Jiajia Xie, Jingjing Shao, Jiexia Wang, Luoqi Huang, Han Lin, Leping Ye, Haolin Chen
Summary: Midazolam has dose-dependent effects on Leydig cell differentiation, with low concentrations increasing testosterone production and high concentrations inhibiting Leydig cell development. Uneven changes in steroidogenic pathway proteins, especially reductions in CYP17A1 at high midazolam levels, may lead to an accumulation of progesterone, potentially impacting male reproduction. Further studies are needed to assess the effects of midazolam on human cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Liza O'Donnell, Penny A. F. Whiley, Kate L. Loveland
Summary: The understanding that Sertoli cells determine fetal testosterone production levels is not widely known, and recent findings suggest this may also be true in humans. The implications of disruptions to Leydig and Sertoli cells on fetal masculinization and reproductive health are significant. This review highlights the importance of further research on how in utero exposures affect organ development in males and females.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Andrology
Ana Planinic, Tihana Maric, Ana Katusic Bojanac, Davor Jezek
Summary: Reinke crystals are unique structures found in Leydig cells, but their molecular composition is still unknown. This review aims to provide a comprehensive guide to understanding the characteristics of Reinke crystals and identifying potential protein candidates.
Article
Environmental Sciences
Qiqi Zhu, Shanshan Zhu, Qiyao Li, Yun Wang, Dongxu Zheng, Chunjiang Chen, Naqi Ruan, Haiqiong Chen, Haoni Yan, Han Lin, Ren-Shan Ge
Summary: Exposure to MTBE during late puberty compromises the development of Leydig cells in male rats by inhibiting cell proliferation, inducing mitochondrial autophagy and apoptosis, and indirectly stimulating Sertoli cells to secrete anti-Mullerian hormones, resulting in a reduced number of Leydig cells.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Review
Endocrinology & Metabolism
Anne Jorgensen, Terje Svingen, Harriet Miles, Tarini Chetty, Jan-Bernd Stukenborg, Rod T. Mitchell
Summary: This article reviews the relationship between the development of the male reproductive system and DSD and TDS, and describes the experimental systems using animal and human tissues or cells that can be used to investigate the role of environmental factors in inducing male reproductive disorders. Finally, the evidence from experimental and epidemiologic approaches for the role of environmental factors in the development of specific male reproductive disorders, including cryptorchidism, hypospadias, and TGCC, is discussed.
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Article
Andrology
Nina Morup, Ailsa Maria Main, Niels Jorgensen, Gedske Daugaard, Anders Juul, Kristian Almstrup
Summary: This study is the first to report the identification of microbiome species in the seminal plasma of men with TGCT and GCNIS-only, and has found some species differences that may be involved in the pathogenesis of TGCTs. Further studies are needed to confirm these findings.
Article
Oncology
Julie Abildgaard, Hein Vincent Stroomberg, A. Kirstine Bang, Jakob Albrethsen, Laura Smedegaard Kruuse, Anders Juul, Klaus Brasso, Andreas Roder, Niels Jorgensen
Summary: Men with high-risk, non-metastatic prostate cancer receive adjuvant androgen deprivation therapy (ADT) for at least 2 years according to Danish guidelines. It remains unclarified if patients regain the function of the pituitary-testis axis after cessation of ADT. Our study investigated the function of the pituitary-testis axis following adjuvant ADT and found that persistent testosterone deficiency (TD) is a common long-term consequence, equally distributed between pituitary and testicular dysfunction. The study emphasizes the necessity for systematic follow-up of full pituitary-testis axis function in patients receiving adjuvant ADT.
ENDOCRINE-RELATED CANCER
(2023)
Review
Obstetrics & Gynecology
Sara Di Persio, Nina Neuhaus
Summary: This review provides an overview of the increasing amount of single-cell RNA-sequencing data in the field of human male reproduction. Transcriptional profiles of thousands of testicular cells covering different developmental stages and male infertility have been generated. The review also discusses novel concepts regarding spermatogonial and somatic cell subtypes and their crosstalk, and provides corresponding marker genes for identification. Furthermore, it explores the potential clinical implications of scRNA-seq findings, the need for spatial information, and the necessity to validate results at other regulatory levels.
HUMAN REPRODUCTION
(2023)
Article
Obstetrics & Gynecology
A. H. Hansen, L. Priskorn, L. S. Hansen, E. Carlsen, U. N. Joensen, F. M. Jacobsen, C. F. S. Jensen, N. Jorgensen
Summary: This study aimed to investigate whether prior testicular torsion is associated with testicular function in young men from the general population. The results showed no differences in semen parameters between men who had experienced testicular torsion and controls. However, subtle alterations in reproductive hormones were observed, with higher FSH and lower inhibin B levels in men with prior testicular torsion. Follow-up studies are needed to assess any long-term consequences for fertility.
HUMAN REPRODUCTION
(2023)
Review
Obstetrics & Gynecology
Hagai Levine, Niels Jorgensen, Anderson Martino-Andrade, Jaime Mendiola, Dan Weksler-Derri, Maya Jolles, Rachel Pinotti, Shanna H. Swan
Summary: This study reveals a significant decline in sperm count among men from all continents, with a more pronounced decrease observed post-2000. The decline in sperm count is not limited to North America-Europe-Australia, but also seen in South/Central America-Asia-Africa. Urgent research and action are needed to investigate the causes and prevent further disruption of male reproductive health.
HUMAN REPRODUCTION UPDATE
(2023)
Article
Oncology
P. L. Jorgensen, M. Kreiberg, N. Jorgensen, A. Juul, P. S. Oturai, C. Dehlendorff, J. Lauritsen, T. Wagner, J. Rosenvilde, G. Daugaard, C. R. Medici, N. R. Jorgensen, M. Bandak
Summary: The aim of this study was to evaluate the metabolic profile and bone mineral density (BMD) changes in testicular cancer survivors with mild Leydig cell insufficiency after 12 months of testosterone replacement therapy (TRT). The results showed that TRT did not significantly affect BMD, but it resulted in a small increase in N-terminal propeptide of type 1 procollagen (P1NP), which had little clinical significance.
Article
Medicine, General & Internal
Rune Holt, Sam Kafai Yahyavi, Ireen Kooij, Christine Hjorth Andreassen, Anna-Maria Andersson, Anders Juul, Niels Jorgensen, Martin Blomberg Jensen
Summary: This study investigated the role of circulating AMH in men and found that low serum AMH is associated with severely impaired gonadal function. Vitamin D supplementation had no effect on serum AMH.
Article
Developmental Biology
Chiara Capponi, Martina Palazzoli, Sara Di Persio, Stefania Fera, Gustavo Spadetta, Giorgio Franco, Joachim Wistuba, Stefan Schlatt, Nina Neuhaus, Dirk de Rooij, Elena Vicini
Summary: In this study, the expression profile of spermatogonial markers during the seminiferous epithelial cycle in cynomolgus monkeys was analyzed and compared with human data. It was found that undifferentiated spermatogonia are largely quiescent, with only a few engaged in the cell cycle and immunoreactive to GFRA1 antibodies, similar to humans. Additionally, a novel subset of early differentiating spermatogonia was described, suggesting that the first generation of differentiating spermatogonia arises early during the epithelial cycle. This study provides important advances in understanding male germline premeiotic expansion in primates.
Article
Biochemistry & Molecular Biology
Verena Hoeffken, Sara Di Persio, Sandra Laurentino, Margot J. Wyrwoll, Nicole Terwort, Anke Hermann, Albrecht Roepke, Manon S. Oud, Joachim Wistuba, Sabine Kliesch, Hermann J. Pavenstaedt, Frank Tuettelmann, Nina Neuhaus, Joachim Kremerskothen
Summary: The WWC protein family regulates cell proliferation and organ growth control via the Hippo signaling pathway. WWC2 has a relatively high expression in the testis and is associated with spermatogenesis and male fertility. Rare variants of the WWC2 gene may be linked to male infertility.
Article
Public, Environmental & Occupational Health
Nina Vogel, Hanne Frederiksen, Rosa Lange, Niels Jorgensen, Holger M. Koch, Till Weber, Anna-Maria Andersson, Marike Kolossa-Gehring
Summary: It has been observed over the past 25 years that exposure to certain phthalates can have negative effects on human health, such as disrupting the endocrine system. As a result, the EU implemented regulations which led to a decrease in production of restricted phthalates and an increase in the production of substitutes. A recent study examined the impact of these regulations on exposure patterns in two European populations.
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2023)
Article
Multidisciplinary Sciences
Katie L. Ayers, Stefanie Eggers, Ben N. Rollo, Katherine R. Smith, Nadia M. Davidson, Nicole A. Siddall, Liang Zhao, Josephine Bowles, Karin Weiss, Ginevra Zanni, Lydie Burglen, Shay Ben-Shachar, Jenny Rosensaft, Annick Raas-Rothschild, Anne Jorgensen, Ralf B. Schittenhelm, Cheng Huang, Gorjana Robevska, Jocelyn van den Bergen, Franca Casagranda, Justyna Cyza, Svenja Pachernegg, David K. Wright, Melanie Bahlo, Alicia Oshlack, Terrence J. O'Brien, Patrick Kwan, Peter Koopman, Gary R. Hime, Nadine Girard, Chen Hoffmann, Yuval Shilon, Amnon Zung, Enrico Bertini, Mathieu Milh, Bochra Ben Rhouma, Neila Belguith, Anu Bashamboo, Kenneth McElreavey, Ehud Banne, Naomi Weintrob, Bruria BenZeev, Andrew H. Sinclair
Summary: We identified recessive variants in SART3 gene in individuals with intellectual disability, global developmental delay, brain anomalies, and gonadal dysgenesis. Further research in fruit flies and human induced pluripotent stem cells revealed the conserved role of SART3 in testicular and neuronal development, and disruption of signaling pathways and abnormal gonadal and neuronal differentiation caused by SART3 variants. These findings suggest that SART3 variants may cause a spliceosomopathy named INDYGON syndrome and contribute to improved diagnoses and outcomes for affected individuals.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Federica Innocenti, Sara Di Persio, Marilena Taggi, Roberta Maggio, Pina Lardo, Vincenzo Toscano, Rita Canipari, Elena Vicini, Antonio Stigliano
Summary: Mitotane (MTT) is the preferred treatment for adrenocortical carcinoma. This study aimed to evaluate the impact of MTT on male gonadal function and propose a sperm cryopreservation program for male patients of childbearing age. The results showed that MTT negatively affects the male reproductive system, including changes in testicular tissue morphology and reductions in sperm concentration and quality.
Article
Hematology
Signe Micas Pedersen, Claus Larsen Feltoft, Torsten Holm Nielsen, Peter de Nully Brown, Anne Ortved Gang, Lars Moller Pedersen, Niels Jorgensen
Summary: This study reports the prevalence of male testosterone deficiency among long-term male survivors of malignant lymphoma. It shows that for screening purposes, an initial measurement of total testosterone may be sufficient in some survivors, but subnormal concentrations of calculated free testosterone were found in 15% of the survivors. Intense treatment for Hodgkin lymphoma and older age were identified as high-risk factors for testosterone deficiency. Pituitary downregulation was also observed. Overall, longitudinal measurements of total testosterone alone may not be adequate for screening testosterone deficiency in all long-term lymphoma survivors.
ANNALS OF HEMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Cecilie Melau, Berta Gayete Mor, Malene Lundgaard Riis, John E. Nielsen, Eva Dreisler, Kasper Aaboe, Pia Tutein Brenoe, Lea Langhoff Thuesen, Kristine Juul Hare, Rod T. Mitchell, Hanne Frederiksen, Anders Juul, Anne Jorgensen
Summary: Administration of dexamethasone (DEX) is effective in suppressing androgenization of external genitalia in fetuses with congenital adrenal hyperplasia. However, the underlying biological mechanism of DEX on fetal development is unknown. This study aimed to investigate the direct effects of DEX on human fetal adrenal (HFA) steroidogenic activity and its influence on the response to ACTH stimulation.
FRONTIERS IN ENDOCRINOLOGY
(2023)