Abstract
Cancer therapy and conditioning treatments of non-malignant diseases affect spermatogonial function and may lead to male infertility. Data on the molecular properties of spermatogonia and the influence of disease and/or treatment on spermatogonial subpopulations remain limited. Here, we assessed if the density and percentage of spermatogonial subpopulation changes during development (n = 13) and due to disease and/or treatment (n = 18) in tissues stored in fertility preservation programs, using markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC). Throughout normal prepubertal testicular development, only the density of 5mC-positive spermatogonia significantly increased with age. In comparison, patients affected by disease and/or treatment showed a reduced density of UTF1-, PCNA- and 5mC-positive spermatogonia, whereas the percentage of spermatogonial subpopulations remained unchanged. As an exception, sickle cell disease patients treated with hydroxyurea displayed a reduction in both density and percentage of 5mC- positive spermatogonia. Our results demonstrate that, in general, a reduction in spermatogonial density does not alter the percentages of undifferentiated and proliferating spermatogonia, nor the establishment of global methylation. However, in sickle cell disease patients’, establishment of spermatogonial DNA methylation is impaired, which may be of importance for the potential use of this tissues in fertility preservation programs.
Highlights
Male reproductive potential depends on the presence and development of the spermatogonial cell population, which forms the basis for spermatogenesis following puberty
Quantification of spermatogonial density in testicular cross sections (Table S2) from patients included in the NT group revealed a linear tendency of increase throughout testicular development in the density of spermatogonia expressing MAGEA4 (Figure 1A,B), undifferentiated embryonic cell transcription factor 1 (UTF1) (Figure 1C,D), and proliferating cell nuclear antigen (PCNA) (Figure 2A,B), without statistical significance
We found that the percentage of MAGEA4, UTF1, PCNA, and 5mC-positive spermatogonia in the AT patient group was not statistically different from the NT gr3o.4u.pS(pFerigmuarteog4o)n.ial Marker Expression in Patients with Cryptorchidism, Sickle Cell Disease and Thalassemia
Summary
Male reproductive potential depends on the presence and development of the spermatogonial cell population, which forms the basis for spermatogenesis following puberty. Impairment of spermatogonial development before or during puberty may lead to infertility in adult life. Reasons for this include pathological conditions such as cryptorchidism and genetic or endocrine disorders [1,2,3,4,5]. Cryopreservation of testicular biopsies containing spermatogonia is the current strategy to preserve reproductive potential of prepubertal patients. Several approaches are investigated, spermatogonia-based fertility restoration methods to derive sperm from stored testicular tissues remain experimental [14]. Descriptive and qualitative information of the heterogeneous prepubertal testicular tissues is pivotal to determine its potential use in fertility restoration strategies. While accumulating evidence on spermatogonial numbers in bio-banked tissues is reported, evaluation of molecular properties of spermatogonia remains limited [4,5,9,10,15]
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