Changes in Expression of Specific mRNA Transcripts after Single- or Re-Irradiation in Mouse Testes

Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species (Spo11, Tnp1, Gfra1, Oct4, Sycp3, Ddx4, Boll, Crem, Prm1, and Acrosin). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species (Claudin-11,Espn, Fshr, GATA1, Inhbb, and Wt1) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation (Aqp8, Clu, Cst12, and Wnt5a) and re-irradiation (Tjp1, occludin,ZO-1, and ZO-2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.

Changes in Expression of Specific mRNA Transcripts after Single- or Re-Irradiation in Mouse Testes

Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species (Spo11, Tnp1, Gfra1, Oct4, Sycp3, Ddx4, Boll, Crem, Prm1, and Acrosin). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species (Claudin-11, Espn, Fshr, GATA1, Inhbb, and Wt1) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation (Aqp8, Clu, Cst12, and Wnt5a) and re-irradiation (Tjp1, occludin, ZO-1, and ZO-2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.

Flurochloridone Induced Abnormal Spermatogenesis by Damaging Testicular Sertoli Cells in Mice

BackgroundFlurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity which evidence is limited and the mechanism is still unclear. The present study was conducted to systematically explore the male reproductive toxicity of FLC, including sperm quality, spermatogenesis process, toxicity targets and possible mechanisms. MethodsMale C57BL/6 mice aged 6-7 weeks received gavage administration of FLC (365/730 mg/kg body weight) for 28 consecutive days. Then the tissue and sperm of mice were collected for analysis. We measured the coefficient of male reproductive organs, and analyzed sperm concentration, motility, malformation rate and mitochondrial membrane potential. Spermatocyte immunofluorescence staining was performed to analyze meiosis processes. At the same time, we performed pathological staining on the testis and epididymis tissue, and performed TUNEL staining, immunohistochemical analysis and ultrastructural observation on the testicular tissue.ResultsThe results showed that FLC caused mice testicular weight reduction, dysfunction and architectural damage, but no significant adverse effect was found in epididymis. The exposure interfered with the proliferation of spermatogonia and the process of meiosis, affecting sperm concentration, motility, kinematic parameters, morphology and mitochondrial membrane potential, leading to sperm quality decline. Furthermore, mitochondrial damage and apoptosis of testicular Sertoli cells were observed in mice treated with FLC. ConclusionWe found that FLC has significant adverse effects on spermatogonia proliferation and meiosis. Meanwhile, apoptosis and mitochondrial damage may be the potential mechanism of Sertoli cell damage. Our study demonstrated that FLC could induce testicular Sertoli cell damage, leading to abnormal spermatogenesis which resulted in sperm quality decline and provided a methodological reference for related studies.

Novel Bi-Allelic Variants of FANCM Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia

Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for the majority of NOA remain unknown. FANCM is a member of Fanconi Anemia (FA) core complex, whose defects are associated with cell hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. It was reported that variants in FANCM (MIM: 609644) might cause azoospermia or oligospermia. However, there is still a lack of evidence to explain the association between different FANCM variants and male infertility phenotypes. Herein, we identified compound heterozygous variants in FANCM in two NOA-affected brothers (c. 1778delG:p. R593Qfs*76 and c. 1663G > T:p. V555F), and a homozygous variant in FANCM (c. 1972C > T:p. R658X) in a sporadic case with NOA, respectively. H&E staining and immunohistochemistry showed Sertoli cell-only Syndrome (SCOS) in the three patients with NOA. Collectively, our study expands the knowledge of variants in FANCM, and provides a new insight to understand the genetic etiology of NOA.

Sertoli cell tumor of the testis causing intracranial metastasis two years after orchiectomy. Report of a rare case and review of the literature

Sertoli cell tumor of the testis (SCTT) accounts for less than 1% of all testicular tumors with only 10% of cases exhibiting malignant behavior. In the present report, a case of malignant SCTT causing multiple metastases in a 32-year-old man is described. After being diagnosed and treated for bone and lymph nodes metastases, the patient presented with a brief history of worsening headaches and visual impairment. A head MRI demonstrated an extra-axial tumor located in the right fronto-parietal junction exhibiting avid contrast enhancement and leptomeningeal involvement. To the best of the authors’ knowledge, this represents the second case of intracranial metastasis from SCTT described to date.