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Spermatogenesis revisited. III. The course of spermatogenesis in a male-sterile pink-eyed mutant type in the mouse.

Male mice homozygous for the recessive p-locus allele ps are sterile. Spermatogenesis is normal through the completion of meiosis, but is abnormal from the Golgi phase of spermiogenesis on. During acrosome formation various abnormalities appear, ranging from atypical Golgiacrosome complexes to multiple acrosome "implantation" sites on the spermatid nuclei. In many developing acrosomal caps the distribution of acrosomal material is irregular. During the nuclear elongation phase, bundles of microtubules oriented parallel to the manchette have been seen lying in cylindrical invaginations of some spermatid nuclei. In later spermatids, chromatin condensation appears to proceed normally but may be unduly delayed in reaching completion. These various perturbations give rise to a wide spectrum of abnormal spermatozoa ranging from spermatozoa with heads of near-normal morphology to highly bizarre heads which have lost their chromatin. Sperm flagellar ultrastructure is normal and all sperm tails; even those devoid of recognizable heads, are highly motile. These findings support the view that the development of the sperm head is under the control of a group of genes distinct from those mediating events involved in flagella development.

Acrosome

Relation of gonadotropin secretion by pituitary grafts to spermatogenesis in hypophysectomized rats.

In hypophysectomized male rats, 2 anterior pituitary (AP) grafts placed underneath the kidney capsule partially prevented atrophy of the testes and ventral prostate during a 17 day post-implantation period. Spermatogenesis was partially maintained as revealed by histological examination of the testes. The AP grafts released small amounts of LH and FSH and substantial amounts of prolactin as determined by radioimmunoassay. Serum LH and FSH were undetectable in the hypophysectomized rats with no AP grafts. Inhibition of prolactin release by daily injections of ergocornine methanesulfonate (ERG) did not significantly alter serum levels of FSH and LH, spermatogenesis or testes and ventral prostate weights, indicating that circulating levels of prolactin were not responsible for the partial maintenance of spermatogenesis and prostate weight in these rats. Daily injections of ovine prolactin also had no effect on spermatogenesis or prolactin also had no effect on spermatogenesis or prostate weight in the hypophysectomized rats, and there was no change in the histological appearance of the testes and prostate. These observations indicate that secretion of gonadotropins and not prolactin by AP grafts accounts for the partial maintenance of spermatogenesis and prostate weight in hypophysectomized, AP-grafted male rats during the experimental period studied.

Animals

Maintenance of spermatogenesis induced by HMG treatment by means of continuous HCG treatment in hypogonadotrophic men.

In a long-term hypophysectomized male HCG treatment was unable to initiate spermatogenesis. However, a spermatogenesis induced by HMG/HCG treatment could be maintained by HCG alone for 7 years with clinical fertility. In another hypogonadotrophic male HCG was also unable to initiate spermatogenesis. But a spermatogenesis once induced by HMG/HCG treatment could be maintained for more than one year with HCG alone. It is suggested that gonadotrophin treatment of the hypogonadotrophic male should consist of HMG + HCG until complete spermatogenesis is induced followed by maintenance treatment with HCG.

Adult

Spermatogenesis and the role of Sertoli cells in the freshwater snail Biomphalaria glabrata.

The various stages of spermatogenesis and the Sertoli cells of Biomphalaria glabrata were studied with histochemical and electron microscope techniques. During spermatogenesis a manchette of microtubules is formed around the nucleus and the mid-piece of the spermatids. This manchette becomes helically coiled and probably plays an important role in the spiralisation of the nucleus and of the mitochondrial sheath. During spermatogenesis so-called chromatoid bodies (CB) occur, which consist of arginine-rich proteins. These CB disintegrate during the early spermatid stage. The results suggest that the CB are either involved in histone transition or in the formation of microtubules. The remaining cytoplasm of the spermatids is phagocytised by the Sertoli cells. Apparently this process of phagocytosis is an important part of the mechanism of spermiation. Morphological measurements of the Sertoli cells showed that the relative volume of most organelles decrease during spermatogenesis, indicating a general decrease in cell activity. Possible functions of the Sertoli cells, such as transportation and nutrition of spermatogenic cells and hormone production, are discussed. It is concluded on the basis of the histochemical and ultrastructural observations that the Sertoli cells are involved in the nutrition of spermatogenic cells. It seems unlikely that they are hormone producing cells.

Animals

Histone synthesis and replacement during spermatogenesis in the mouse.

Separation of labelled nuclei by sedimentation velocity at unit gravity (Staput method) was used to study the timing of histone synthesis and replacement by testis-specific basic nuclear protein (TSP) during spermatogenesis in the mouse. Animals were injected (intratesticularly) with 1.25 micronCi per testis 3H-arginine or 2.5 micronCi per testis 3H-lysine, testis nuclei were separated, and the acid extract of each nuclear fraction was analyzed by acrylamide gel electrophoresis. The distribution of labelled histones and TSP in separated nuclei was assessed 2 h after incorporation. Changes in the labelled histone and TSP content of nuclei during subsequent differentiation (1--34 days post-label) was followed in fractions of separated testis cell nuclei and in nuclei of cauda epididymal spermatozoa. Analysis of total histone and (TSP) content indicated quantitative changes during development. Nuclei from primary spermatocytes had relatively larger amounts of histones H1 and H4. Spermatid nuclei showed a relative reduction in histones H1 and H4, coincident with the appearance of TSP in these nuclei. These results suggested that synthesis and/or removal of certain histones must occur in late primary spermatocyte and early spermatid stages of spermatogenesis. Results of labelling experiments indicated several periods of histone synthesis during spermatogenesis: (1) closely associated with the last DNA synthesis(i.e., in early primary spermatocytes), (2) late in meiotic prophase (i.e., in pachytene primary spermatocytes) and (3) simultaneous with TSP synthesis (i.e., in late spermatids). Histone H1 was more heavily labelled toward the end of the primary spermatocyte period. Histone H4 was more heavily labelled in the early primary spermatocyte period, and again at the time of TSP synthesis in spermatids. Histones synthesized before the pachytene primary spermatocyte stage appeared to be replace, but histones synthesized later in spermatogenesis appeared to be at least partially retained in epididymal spermatozoa. These results suggested that repeated specific alterations in the protein complement of the nucleus are an integral part of spermatogenic differentiation in the mouse.

Animals

Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis-version 1.

OBJECTIVE: To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS: Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES: the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95% CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS: We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS: In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

Humans

Spermatogenesis in hybrid mice treated with oestrogen and testosterone.

Male BC3F1 hybrid mice were injected with 10 micrograms oestradiol benzoate/day alone or in conjunction with 80 micrograms testosterone propionate/day. Oestrogen alone decreased the weights of the accessory sex organs, but oestrogen + testosterone resulted in an increase. Assessment of spermatogenesis by a variety of methods revealed little effect of the hormones. Testicular weight and the histological appearance of the seminiferous epithelium was not altered appreciably, although Leydig cell atrophy was apparent when testosterone was given. The kinetics of spermatogenesis, studied by cell separation techniques and biochemical features of spermatogenesis, including protamine biosynthesis, lactate dehydrogenase levels and the formation of the highly resistant, condensed sperm nucleus, were also unaffected by the hormonal treatments. However, a reduction in the number of intact testicular spermatozoa in mechanically prepared cell suspensions was obtained. It is concluded that, in these animals, spermatogenesis is relatively insensitive to the administration of oestrogen.

Animals

Return of spermatogenesis after stopping cyclophosphamide therapy.

A follow-up of twenty-six male patients with azoospermia after stopping cyclophosphamide treatment showed a return of spermatogenesis in twelve patients within 15-49 months (mean 31 months). In one patient spermatogenesis returned despite 34 months of treatment with 100 mg. of cyclophosphamide daily. The period of follow-up after stopping cyclophosphamide therapy varied from 5 months to 4 years. After 6 months on cyclophosphamide all patients remained azoospermic while taking the drug. Return of spermatogenesis was not significantly associated with age, duration of cyclophosphamide therapy, total dose, or time of follow-up after stopping treatment; however, the number of patients in the study was small.

Adult

Mosaic character of spermatogenesis in carriers of the sex reversed factor in the mouse.

The "sex reversed" factor leads to development of XX male mice. It is inherited on one of the autosomes and transmitted through XY-Sxr carrier males. In the latter, spermatogenesis is studied under the aspect of gene dosis effects produced by the presence of the Sxr factor in addition to the Y chromosome. A mosaic pattern of normal and defective spermatogenesis is described. The defective areas are characterized by failure in late pachytene and metaphase I, and by appearance of spermatids with very large nuclei which degenerate in cap phase. The defects correspond to those observed in X0-Sxr spermatogenesis. Our interpretation is that in the normal areas only the Y chromosome, and in the defective areas the Sxr factor is expressed.

Androgen-Insensitivity Syndrome

Recognition of differentiation antigens of spermatogenesis in the mouse by using antibodies from spleen cell-myeloma hybrids after syngeneic immunization.

Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are species but not strain specific and trypsin sensitive but collagenase insensitive. On the basis of their appearance during the onset of spermatogenesis they appear to be differentiation antigens expressed during different but overlapping time windows during spermatogenesis.

Animals

Gene expression of a region of chromosome 17 during murine spermatogenesis.

The presence of H-2-linked gene products on spermatozoa and their time of appearance during spermatogenesis was determined. Thymus leukaemia antigen specificities 1, 2 and 3 could not be detected on spermatozoa by absorption of the antisera. Immunofluorescent studies with anti-Slp sera did not reveal any specific reactivity with target spermatozoa. In contrast, H-2D antigens were present on somatic as well as germ line components in testes so the time of their first appearance during spermatogenesis could not be precisely specified. Cell separation experiments indicate that H-2D antigens are present on pachytene spermatocytes and increased in quantity on spermatids. The sperm-specific isoenzyme of phosphoglycerate kinase, Pgk-2, appears at a later stage of spermatogenesis than do the H-2 region antigens.

Aging

The dynamics of Drosophila melanogaster spermatogenesis in in vitro cultures.

A photographic description of meiosis and spermatogenesis in single sperm cysts of Drosophila melanogaster cultured in vitro is presented. In addition to the utility of this description for the study of spermatogenesis in whole live testes, the culture procedure provides a means for studying the dynamic development of individual sperm cysts from flies carrying male-sterile mutations, as illustrated with X/O males. Several deviations of spermatogenesis in vitro from that in vivo suggest that sperm morphogenesis is not rigidly coordinated.

Animals

The effect of prostaglandins and prostaglandin inhibitors on spermatogenesis.

The effect of the prostaglandin inhibitors, aspirin and indomethacin and of prostaglandins PGE1 and PGE2 on spermatogenesis in the mature male mouse has been studied. Aspirin at 100 mg/kg and at 200 mg/kg, and indomethacin at 1.0 mg/kg given orally twice a day for fifteen days produced a marked increase in spermatogenesis. The number of step 7 spermatids increased significantly over controls at about the same rate in all three groups. No significant changes in seminal vesicle weight or testicular weight was noted, although testicular weight did show an increase. Administration of prostaglandins E1 and E2 subcutaneously in doses of either 2 mg/kg or 3 mg/kg once a day for fifteen days produced a marked decrease in spermatogenesis. Step 7 spermatids decreased significantly at both dosage levels of PGE2 and at the higher dosage level of PGE1. Spermatocyte showed a significant decrease at the higher dose of PGE2. Testicular weight showed a significant decrease at the higher dose of PGE2. Seminal vesicle weight showed a significant decrease at the lower dose of PGE1 and at the higher dose of PGE2. Epididymal weight decreased at the higher dose of PGE2. Increased numbers of exfoliated immature germ cells and mature spermatozoa were observed in the epididymus of both the PGE1 and PGE2 treated animals.

Animals

Effect of oestrogenic, and androgenic and gestagenic hormones on the gametogenesis (oogenesis and spermatogenesis) in the snail Helix pomatia.

In the ovotestis of Helix pomatia both oogenesis and spermatogenesis were influenced by treatments with steroid hormones produced in the gonads of higher vertebrates. Testosterone influenced gametogenesis to a small degree. Progesterone and oestrone-acetate at first stimulated ovogenesis, but they also acted on spermatogenesis. All three hormones examined influenced oogenesis in a conspicuous and significant way, while their effect on spermatogenesis was indistinct.

Animals

[Spermatogenesis in dogs during chronic gamma irradiation over years and in the aftereffect period].

Morphological parameters of spermatogenesis of 60 test and 12 control dogs exposed to a 6-year irradiation with total doses of 21 to 1140 rad were studied. The capacity for reparative regeneration of testes was maintained during the 5-6 years of irradiation at a dose rate of 0.06 and 0.17 rad/day. Early signs of radiation injury of testes were clearly observed during the first years of irradiation at a dose rate of 125 rad/year and progressively developed with an increase in the total dose. Inhibition of spermatogenesis reached maximum (atrophy of the spermatogenic epithelium, depletion of canaliculi) by the end of the first year of combined irradiation (190 rad/year). Spermatogenesis returned to normal in the animals that received a total dose of 570 rad during a 3-year irradiation exposure and were sacrificed 4.5 years after the onset of the experiment.

Animals