Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

<b>Background</b>: Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM.<BR/> <b>Methods</b>: This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice.<BR/> <b>Results</b>: Microscopic TM was seen in 94% of hpg.ARKO mice (n=16) and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n=11) of hpg testes (mean 2 +/- 0.5 per testis) and 30% (n=10) of hpg.SCARKO testes (mean 8 +/- 6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice.<BR/> <b>Conclusions</b>: We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression

Selective electroless deposition of cobalt using amino-terminated SAMs

© 2019 The Royal Society of Chemistry. The continuation of CMOS scaling leads to the necessity of replacing Cu as an interconnect material with a metal with lower resistivity and better reliability performance. At the same time, significant technological improvements are required to mitigate the pattern overlay requirements when forming multilevel structures with a half-pitch below 10 nm. Area-selective deposition (ASD) offers an elegant way to enable self-alignment of multilevel structures. However, defectivity is a typical bottleneck of ASD integration. This work explores the selective electroless deposition (ELD) of Co as a replacement of Cu as an interconnect metal. The selective metallization process is promoted by the selective placement of an amino-terminated organic layer in combination with confined grafting of a Pd catalyst. Co films thicker than 40 nm can be formed on amino-terminated surfaces, while the surfaces with no amino functionality remain completely free of Pd and Co according to EDS chemical analysis and SEM inspection. This article offers a detailed study of selective Co growth on blanket and patterned structures and investigation of the ELD Co film properties, such as low-temperature recrystallization at 420 °C, grain structure, chemical composition and segregation of impurities. It is demonstrated that the resistivity of the ELD Co films exhibits lower thickness dependence when compared to that of PVD Co, which can be attributed to the ELD Co grain size exceeding the Co film thickness. In addition, it is shown that the underlying organic layer prevents the silicidation of the annealed Co film on the Si substrate while promoting interface adhesion values as high as 8.2 J m -2 ± 0.7 J m -2 for a 50-nm thick Co film.status: publishe

Selective electroless deposition of cobalt using amino-terminated SAMs

The continuation of CMOS scaling leads to the necessity of replacing Cu as an interconnect material with a metal with lower resistivity and better reliability performance. At the same time, significant technological improvements are required to mitigate the pattern overlay requirements when forming multilevel structures with a half-pitch below 10 nm. Area-selective deposition (ASD) offers an elegant way to enable self-alignment of multilevel structures. However, defectivity is a typical bottleneck of ASD integration. This work explores the selective electroless deposition (ELD) of Co as a replacement of Cu as an interconnect metal. The selective metallization process is promoted by the selective placement of an amino-terminated organic layer in combination with confined grafting of a Pd catalyst. Co films thicker than 40 nm can be formed on amino-terminated surfaces, while the surfaces with no amino functionality remain completely free of Pd and Co according to EDS chemical analysis and SEM inspection. This article offers a detailed study of selective Co growth on blanket and patterned structures and investigation of the ELD Co film properties, such as low-temperature recrystallization at 420 degrees C, grain structure, chemical composition and segregation of impurities. It is demonstrated that the resistivity of the ELD Co films exhibits lower thickness dependence when compared to that of PVD Co, which can be attributed to the ELD Co grain size exceeding the Co film thickness. In addition, it is shown that the underlying organic layer prevents the silicidation of the annealed Co film on the Si substrate while promoting interface adhesion values as high as 8.2 J m(-2) +/- 0.7 J m(-2) for a 50-nm thick Co film

Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

Abstract Background Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM. Methods This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice. Results Microscopic TM was seen in 94% of hpg.ARKO mice (n = 16) and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n = 11) of hpg testes (mean 2 +/- 0.5 per testis) and 30% (n = 10) of hpg.SCARKO testes (mean 8 +/- 6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice. Conclusion We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression.</p

Reproductive Biology and Endocrinology Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

Abstract Background: Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM

Postnatal testis development, Sertoli cell proliferation and number of different spermatogonial types in C57BL/6J mice made transiently hypo- and hyperthyroidic during the neonatal period

The role of thyroid hormones in testis structure and function has been fairly well studied in laboratory rodents. However, there are no comprehensive data in the literature for mice regarding the effects of transiently induced neonatal hypo- and hyperthyroidism on testis and spermatogonial cell development from birth to adulthood. Our goals were to evaluate the effects of propylthiouracil (PTU) and triidothyronine (T3) on Sertoli cell proliferation/differentiation and to correlate these events with the evolution of the spermatogenic process, tubular lumen formation, blood vessel volume density, and size and number of different spermatogonial types. Although Sertoli cell maturation was accelerated or delayed, respectively, in T3- and PTU-treated mice, the pace of the germ cell maturation was only slightly altered before puberty and the period of Sertoli cell proliferation was apparently not affected by the treatments. However, compared with controls, the total number of Sertoli cells per testis from 10 days of age to adulthood was significantly increased and decreased in PTU- and T3-treated mice, respectively. In comparison to all other spermatogonia, type A2 was the largest cell in all ages and groups investigated. The PTU-treated mice had a significantly increased total number of undifferentiated spermatogonia as well as volume and percentage of vessels/capillaries, probably due to the higher number of Sertoli cells, particularly at 10 days of age. Taken together, our results suggest that neonatal hypothyroidism may be a valuable tool for studying spermatogonial biology as well as a means for providing more spermatogonial stem cells that could potentially be used for spermatogonial transplantation, thereby optimizing the efficiency of this technique when young mice are used as donors