Tuberoinfundibular Peptide of 39 Residues Is Required for Germ Cell Development

Tuberoinfundibular peptide of 39 residues (TIP39) was identified as a PTH 2 receptor ligand. We report that mice with deletion of Tifp39, the gene encoding TIP39, are sterile. Testes contained Leydig and Sertoli cells and spermatogonia but no spermatids. Labeling chromosome spreads with antibodies to proteins involved in recombination showed that spermatogonia do not complete prophase of meiosis I. Chromosomes were observed at different stages of recombination in single nuclei, a defect not previously described with mutations in genes known to be specifically involved in DNA replication and recombination. TIP39 was previously shown to be expressed in neurons projecting to the hypothalamus and within the testes. LH and FSH were slightly elevated in Tifp39−/− mice, suggesting intact hypothalamic function. We found using in situ hybridization that the genes encoding TIP39 and the PTH 2 receptor are expressed in a stage-specific manner within seminiferous tubules. Using immunohistochemistry and quantitative RT-PCR, TIP39 expression is greatest in mature testes, and appears most abundant in postmeiotic spermatids, but TIP39 protein and mRNA can be detected before any cells have completed meiosis. We used mice that express Cre recombinase under control of a spermatid-specific promoter to express selectively a cDNA encoding TIP39 in the testes of Tifp39−/− mice. Spermatid production and fertility were rescued, demonstrating that the defect in Tifp39−/− mice was due to the loss of TIP39. These results show that TIP39 is essential for germ cell development and suggest that it may act as an autocrine or paracrine agent within the gonads.

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Isolation of the murine cyclin B2 cDNA and characterization of the lineage and temporal specificity of expression of the B1 and B2 cyclins during oogenesis, spermatogenesis and early embryogenesis

Development ◽

10.1242/dev.118.1.229 ◽

1993 ◽

Vol 118 (1) ◽

pp. 229-240 ◽

Cited By ~ 1

Author(s):

D.L. Chapman ◽

D.J. Wolgemuth

Keyword(s):

Germ Cell ◽

Germ Cells ◽

Northern Blot ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Development ◽

Early Embryogenesis ◽

Northern Blot Hybridization ◽

Germ Cell Development

A cDNA encoding the murine cyclin B2 (cycB2) was isolated from an adult mouse testis cDNA library as part of studies designed to identify cyclins involved in murine germ cell development. This cycB2 cDNA was then used to examine the pattern of cycB2 expression during male and female germ cell development and in early embryogenesis, and to compare this expression with the previously characterized expression of cycB1. A single 1.7 kb cycB2 transcript was detected by northern blot hybridization analysis of total RNA isolated from midgestation embryos and various adult tissues. Northern blot and in situ hybridization analyses revealed that cycB2 expression in the testis was most abundant in the germ cells, specifically in pachytene spermatocytes. This is in contrast to the highest levels of expression of cycB1 being present in early spermatids. In situ analysis of the ovary revealed cycB2 transcripts in both germ cells and somatic cells, specifically in the oocytes and granulosa cells of growing and mature follicles. The pattern of cycB1 and cycB2 expression in ovulated and fertilized eggs was also examined. While the steady state level of cycB1 and cycB2 signal remained constant in oocytes and ovulated eggs, signal of both appeared to decrease following fertilization. In addition, both cycB1 and cycB2 transcripts were detected in the cells of the inner cell mass and the trophectoderm of the blastocyst. These results demonstrate that there are lineage- and developmental-specific differences in the pattern of the B cyclins in mammalian germ cells, in contrast to the co-expression of B cyclins in the early conceptus.

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OTOGL, a gelforming mucin protein, is nonessential for male germ cell development and spermatogenesis in mice

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00779-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zhiming Li ◽

Yan Zhang ◽

Xinzong Zhang ◽

Congcong Cao ◽

Xiaomin Luo ◽

...

Keyword(s):

Germ Cell ◽

Knockout Mouse ◽

Histological Analysis ◽

Normal Development ◽

Biological Function ◽

Cell Development ◽

Male Germ Cell ◽

Seminiferous Tubules ◽

Obstructive Azoospermia ◽

Germ Cell Development

AbstractOtogelin-like protein (encoded by Otogl) was highly structural similar to the gelforming mucin proteins. Although human OTOG mutations have been linked to deafness, the biological function of OTOGL in male germ cell development remains enigmatic. In screening 336 patients with non-obstructive azoospermia (NOA), OTOGL displays the high mutant ratio (13.99 %). Then, we examined the expression of OTOGL in developing mouse testes. Otogl mRNA and protein are continually expressed in postnatal developing testes from postnatal day 0 (P0) testes to P21 testes exhibiting a decreased trend with the age growth. We thus generated a global Otogl knockout mouse (KO) model using the CRISPR/Cas9 technology; however, Otogl KO mice displayed normal development and fertility. Further histological analysis of Otogl knockout mouse testes revealed that all types of spermatogenic cells are present in Otogl KO seminiferous tubules. Together, our study suggested that OTOGL is nonessential for male germ cell development and spermatogenesis.

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FSH and testosterone effects in seminiferous tubules of immature hypophysectomized rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.241.3.e233 ◽

1981 ◽

Vol 241 (3) ◽

pp. E233-E237

Author(s):

J. A. Collins ◽

S. Sepsenwol ◽

T. Braun

Keyword(s):

Adenylate Cyclase ◽

Germ Cell ◽

Cell Development ◽

Seminiferous Tubules ◽

Moderate Increase ◽

Late Pachytene ◽

Germ Cell Development ◽

Enzyme Content ◽

Hypophysectomized Rats ◽

Control Sham

The effects of follicle-stimulating hormone (FSH) and testosterone on the development of the cytosolic germ cell adenylate cyclase and germ cell morphology in rats hypophysectomized at 29 days of age were studied. Following hypophysectomy, the adenylate cyclase content fell to marginal levels and germ cell development ceased at the late pachytene stage. Testosterone treatment led to a moderate increase in the cytosolic enzyme content and to progression of spermatid cell development to stages 8–12. FSH treatment with doses of 80–100 micrograms/day restored enzyme content to levels seen in control rats, as well as progression of germ cell development up to stages 15–16, i.e., to the same stages present in age-matched control (sham-operated) rats. The results indicate that in immature rats FSH is essential for spermatid cell maturation as is evidenced by its ability to stimulate the formation of cytosolic germ cell adenylate cyclase to quantitatively normal levels, as well as to stimulate the development of spermatid cells.

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Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors

Oncogene ◽

10.1038/sj.onc.1208543 ◽

2005 ◽

Vol 24 (19) ◽

pp. 3223-3228 ◽

Cited By ~ 76

Author(s):

Uwe M Galli ◽

Marlies Sauter ◽

Bernd Lecher ◽

Simone Maurer ◽

Hermann Herbst ◽

...

Keyword(s):

Germ Cell ◽

Carcinoma In Situ ◽

Germ Cell Tumors ◽

Cell Development ◽

Endogenous Retrovirus ◽

Human Endogenous Retrovirus ◽

Germ Cell Development

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Pou5f1 and Nanog Are Reliable Germ Cell-Specific Genes in Gonad of a Protogynous Hermaphroditic Fish, Orange-Spotted Grouper (Epinephelus coioides)

Genes ◽

10.3390/genes13010079 ◽

2021 ◽

Vol 13 (1) ◽

pp. 79

Author(s):

Chaoyue Zhong ◽

Meifeng Liu ◽

Yuhao Tao ◽

Xi Wu ◽

Yang Yang ◽

...

Keyword(s):

Germ Cell ◽

Germ Cells ◽

Cell Development ◽

Marker Genes ◽

Epinephelus Coioides ◽

Cell Marker ◽

Specific Expression ◽

Germ Cell Development ◽

Somatic Tissues

Pluripotency markers Pou5f1 and Nanog are core transcription factors regulating early embryonic development and maintaining the pluripotency and self-renewal of stem cells. Pou5f1 and Nanog also play important roles in germ cell development and gametogenesis. In this study, Pou5f1 (EcPou5f1) and Nanog (EcNanog) were cloned from orange-spotted grouper, Epinephelus coioides. The full-length cDNAs of EcPou5f1 and EcNanog were 2790 and 1820 bp, and encoded 475 and 432 amino acids, respectively. EcPou5f1 exhibited a specific expression in gonads, whereas EcNanog was expressed highly in gonads and weakly in some somatic tissues. In situ hybridization analyses showed that the mRNA signals of EcNanog and EcPou5f1 were exclusively restricted to germ cells in gonads. Likewise, immunohistofluorescence staining revealed that EcNanog protein was limited to germ cells. Moreover, both EcPou5f1 and EcNanog mRNAs were discovered to be co-localized with Vasa mRNA, a well-known germ cell maker, in male and female germ cells. These results implied that EcPou5f1 and EcNanog could be also regarded as reliable germ cell marker genes. Therefore, the findings of this study would pave the way for elucidating the mechanism whereby EcPou5f1 and EcNanog regulate germ cell development and gametogenesis in grouper fish, and even in other protogynous hermaphroditic species.

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Sertoli and Germ Cell Development in Hypogonadal (hpg) Mice Expressing Transgenic Follicle-Stimulating Hormone Alone or in Combination with Testosterone

Endocrinology ◽

10.1210/en.2002-220710 ◽

2003 ◽

Vol 144 (2) ◽

pp. 509-517 ◽

Cited By ~ 97

Author(s):

Miriam Haywood ◽

Jenny Spaliviero ◽

Mark Jimemez ◽

Nicholas J. C. King ◽

David J. Handelsman ◽

...

Keyword(s):

Germ Cell ◽

Sertoli Cell ◽

Synergistic Effects ◽

Cell Development ◽

Seminiferous Tubules ◽

Germ Cell Development ◽

Cell Numbers ◽

Meiotic Progression ◽

Spermatogonial Proliferation

We recently created a novel transgenic (tg) model to examine the specific gonadal actions of FSH, distinct from LH effects, by expressing tg-FSH in gonadotropin-deficient hypogonadal (hpg) mice. Using this unique in vivo paradigm, we now describe the postnatal cellular development in seminiferous tubules selectively stimulated by tg-FSH alone or combined with testosterone (T). In the αβ.6 line, tg-FSH stimulated the maturation and proliferation (∼2-fold) of Sertoli cells in hpg testes. Total Sertoli cell numbers were also significantly increased (1.5-fold) independently of FSH effects by T treatment alone. Selective FSH activity in αβ.6 hpg testes increased total spermatogonia numbers 3-fold, which established a normal spermatogonia/Sertoli cell ratio. FSH also elevated meiotic spermatocyte numbers 7-fold, notably at pachytene (28-fold), but induced only limited numbers of postmeiotic haploid cells (absent in hpg controls) that arrested during spermatid elongation. In contrast, T treatment alone had little effect on postnatal spermatogonial proliferation but greatly enhanced meiotic progression with total spermatocytes increased 12-fold (pachytene 53-fold) relative to hpg testes, and total spermatid numbers 11-fold higher than tg-FSH hpg testes. Combining tg-FSH and T treatment had no further effect on Sertoli or spermatogonia numbers relative to FSH alone but had marked additive and synergistic effects on meiotic cells, particularly pachytene (107-fold more than hpg), to establish normal meiotic germ cell/Sertoli cell ratios. Furthermore, tg-FSH had a striking synergistic effect with T treatment on total spermatid numbers (19-fold higher than FSH alone), although spermatid to Sertoli cell ratios were not fully restored to normal, indicating elevated Sertoli cell numbers alone are insufficient to establish a maximal postmeiotic germ cell capacity. This unique model has allowed a detailed dissection of FSH in vivo activity alone or with T and provided compelling evidence that FSH effects on spermatogenesis are primarily via Sertoli and spermatogonial proliferation and the stimulation of meiotic and postmeiotic germ cell development in synergy with and dependent on T actions.

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