A Developmental Switch in Gene Expression of Rat Sertoli Cells is Associated with the Initiation of Germ Cell Differentiation.

Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium.Fabp5expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression ofFabp3increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells.Fabp9, together withFabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressedPlin2. Yet, whileDgat1was detected in Sertoli cells,Dgat2accumulated in germ cells with a similar pattern of expression asFabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age- and germ cell type-associated increases inFabp9,Dgat2, andPlin2levels are thus functionally related in the last stages of germ cell differentiation.

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Interrelationships between Germ Cell Differentiation and Transformation of Basolateral Profile of Sertoli Cells during Rat Spermatogonial Cycle

Archives of Histology and Cytology ◽

10.1679/aohc.50.209 ◽

1987 ◽

Vol 50 (2) ◽

pp. 209-221 ◽

Cited By ~ 1

Author(s):

Masao HAMASAKI

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Sertoli Cells ◽

Germ Cell Differentiation

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1 XENOGRAFTING OF ADULT MAMMALIAN TESTIS TISSUE

Reproduction Fertility and Development ◽

10.1071/rdv19n1ab1 ◽

2007 ◽

Vol 19 (1) ◽

pp. 119

Author(s):

L. Arregui ◽

R. Rathi ◽

W. Zeng ◽

A. Honaramooz ◽

M. Gomendio ◽

...

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Germ Cells ◽

Sertoli Cells ◽

Human Testis ◽

Seminiferous Tubules ◽

Donor Tissue ◽

Germ Cell Differentiation ◽

Sexually Mature ◽

Testis Tissue

Testis tissue grafting presents an option for preservation of genetic material when sperm recovery is not possible. Grafting of testis tissue from sexually immature males to immunodeficient mice results in germ cell differentiation and production of fertilization-competent sperm from different mammalian species (Honaramooz et al. 2002 Nature 418, 778–781). However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Spermatogenesis was arrested at meiosis in grafts from mature horses (Rathi et al. 2006 Reproduction 131, 1091–1098) and hamsters (Schlatt et al. 2002 Reproduction 124, 339–346), and no germ cell differentiation occurred in xenografts of adult human testis tissue (Schlatt et al. 2006 Hum. Reprod. 21, 384–389). The objective of this study was to investigate survival and germ cell differentiation of testis xenografts from sexually mature donors of different species. Small fragments of testis tissue from 10 donor animals of 5 species were grafted under the back skin of immunodeficient, castrated male mice (n = 37, 2–6/donor). Donors were pig (8 months old), goat (18 months old and 4 years old) (n = 2), bull (3 years old), donkey (13 months old), and rhesus monkey (3, 6, 11, and 12 years old). At the time of grafting, donor tissue contained elongated spermatids, albeit to different degrees (>75% of seminiferous tubules in testis tissue from pig, goat, bull, and 6–12-year-old monkeys, and 33 or 66% of tubules in tissue from donkey or 3-year-old monkey, respectively). Grafts were recovered <12 weeks (n = 14 mice), 12–24 weeks (n = 16 mice), and >24 weeks (n = 7 mice) after grafting and classified histologically as completely degenerated (no tubules found), degenerated tubules (only hyalinized seminiferous tubules observed), or according to the most advanced type of germ cell present. Grafts from pig, goat, bull, and 6–12-year-old monkeys contained >60% degenerated tubules or were completely degenerated at all time points analyzed. In contrast, in grafts from the 3-year-old monkey, only 18% of tubules were degenerated, 14% contained Sertoli cells only, 64% contained meiotic, and 4% haploid germ cells at 24 weeks after grafting. Similarly, donkey testis grafts recovered 12–24 weeks after grafting contained <2% degenerated tubules, 46% of tubules had Sertoli cells only, 45% contained meiotic, and 7% haploid germ cells. These results show that survival and differentiation of germ cells in testis grafts from sexually mature mammalian donors is poor. However, better graft survival and maintenance of spermatogenesis occurred in donor tissue from donkey and 3-year-old monkey that were less mature at the time of grafting. Therefore, species and age-related differences appear to exist with regard to germ cell survival and differentiation in xenografts from adult donors. This work was supported by USDA/CSREES 03-35203-13486, NIH/NCRR 5-R01-RR17359-05, the Spanish Ministry of Education, and Science (BES-2004-4112).

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Analysis of Drosophila p8 and p52 mutants reveals distinct roles for the maintenance of TFIIH stability and male germ cell differentiation

Open Biology ◽

10.1098/rsob.160222 ◽

2016 ◽

Vol 6 (10) ◽

pp. 160222 ◽

Cited By ~ 4

Author(s):

Grisel Cruz-Becerra ◽

Mandy Juárez ◽

Viviana Valadez-Graham ◽

Mario Zurita

Keyword(s):

Gene Expression ◽

Dna Repair ◽

Cell Differentiation ◽

Germ Cell ◽

Specific Cell ◽

Germ Cell Differentiation ◽

Specific Syndrome ◽

Eukaryotic Gene Expression ◽

Eukaryotic Gene

Eukaryotic gene expression is activated by factors that interact within complex machinery to initiate transcription. An important component of this machinery is the DNA repair/transcription factor TFIIH. Mutations in TFIIH result in three human syndromes: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Transcription and DNA repair defects have been linked to some clinical features of these syndromes. However, how mutations in TFIIH affect specific developmental programmes, allowing organisms to develop with particular phenotypes, is not well understood. Here, we show that mutations in the p52 and p8 subunits of TFIIH have a moderate effect on the gene expression programme in the Drosophila testis, causing germ cell differentiation arrest in meiosis, but no Polycomb enrichment at the promoter of the affected differentiation genes, supporting recent data that disagree with the current Polycomb-mediated repression model for regulating gene expression in the testis. Moreover, we found that TFIIH stability is not compromised in p8 subunit-depleted testes that show transcriptional defects, highlighting the role of p8 in transcription. Therefore, this study reveals how defects in TFIIH affect a specific cell differentiation programme and contributes to understanding the specific syndrome manifestations in TFIIH-afflicted patients.

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318 EFFECT OF 6-N-PROPYL-2-THIOURACIL-INDUCED HYPOTHYROIDISM IN THE HOST MOUSE ON THE DEVELOPMENT OF BOVINE TESTIS XENOGRAFTS

Reproduction Fertility and Development ◽

10.1071/rdv22n1ab318 ◽

2010 ◽

Vol 22 (1) ◽

pp. 315

Author(s):

J. R. Rodriguez-Sosa ◽

G. M. J. Costa ◽

R. Rathi ◽

L. R. França ◽

I. Dobrinski

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Sertoli Cell ◽

Germ Cells ◽

Sertoli Cells ◽

Cell Maturation ◽

Germ Cell Differentiation ◽

Host Mouse ◽

Thyroid Hormone Levels ◽

Collection Time

In rodents, thyroid hormones inhibit Sertoli cell proliferation, promote Sertoli cell differentiation, and accelerate lumen formation in the seminiferous tubules. Conversely, transient hypothyroidism prolongs Sertoli cell proliferation, leading to increased Sertoli cell number and testicular size. In order to evaluate whether 6-N-propyl-2-thiouracil (PTU)-induced hypothyroidism in the host mouse would affect seminiferous tubule development and germ cell differentiation, and subsequently increase spermatogenesis in bovine testis xenografts, fragments (∼1 mm3) of testes from 1-wk-old Holstein calves (n = 6) were transplanted ectopically to castrated immunodeficient male mice (n = 6/donor). Mice (n = 3/donor) were treated with 0.1% (w/v) PTU in drinking water for 4 weeks or left as control. At 5 and 7 months after grafting, grafts were analyzed by morphometry and immunohistochemistry for expression of protein gene product 9.5 (PGP 9.5) as a germ cell marker, and Mullerian-inhibiting substance (MIS) and androgen receptor (AR) to assess Sertoli cell maturation. For each variable, averages of each group were compared at each collection point by t-test PTU treatment to the drinking water for 1 month suppressed thyroid hormone levels (T4) in host mice without negative systemic effects (0.3 ± 0.2 v. 4 ± 0.3 μg dL-1 at 4 weeks in treated v. control mice, respectively, P < 0.05). Spermatogenesis in recovered grafts was arrested at meiosis regardless of treatment and collection time. Graft weight was lower in treated mice than in controls (21 ± 4 v. 42 ± 5 and 24 ± 9 v. 51 ± 5 mg, at 5 and 7 months, respectively, P < 0.05). Volume density of the tubular and intertubular compartments, and seminiferous epithelium, was not affected by treatment (P > 0.05); however, treatment reduced lumen density compared to controls (9 ± 2 v. 19 ± 3 and 12 ± 1 v. 24 ± 4%) and tubular diameter (121 ± 3 v. 140 ± 7 and 144 ± 2v. 170 ± 2 (im, at 5 and 7 months, respectively (P < 0.05). Tubule length per milligram was not different at 5 months between control and treated groups (P > 0.05) but was increased at 7 months in the treated grafts (50 ± 1 v. 30 ± 1 cm, P < 0.05). Number of Sertoli cells per milligram was not affected by treatment (P > 0.05). However, Sertoli cell volume was increased in controls (440 ± 19 v. 341 ± 14 and 504 ± 6 v. 388 ± 18 μm3, at 5 and 7 months, respectively, P < 0.05). The number of germ cells per 100 Sertoli cells was not different between groups at any collection time (P > 0.05). Sertoli cells showed variable MIS expression and lack of or weak AR expression regardless of treatment and collection time, indicating an immature phenotype. In conclusion, suppression of thyroid hormone levels in host mice affects seminiferous tubule development in bovine testis xenografts, demonstrating that endocrine manipulation of the mouse host will affect xenografts in a predictable manner. However, treatment did not affect number and differentiation of germ cells. Rather, incomplete Sertoli cell maturation appears to lead to incomplete germ cell differentiation in bovine testis xenografts. Supported by USDA (2007-35203-18213).

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Effect of Gosha-Jinki-Gan on Levels of Specific mRNA Transcripts in Mouse Testes after Busulfan Treatment

Biomedicines ◽

10.3390/biomedicines8100432 ◽

2020 ◽

Vol 8 (10) ◽

pp. 432

Author(s):

Ning Qu ◽

Kenta Nagahori ◽

Miyuki Kuramasu ◽

Yuki Ogawa ◽

Kaori Suyama ◽

...

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Cancer Patients ◽

Sertoli Cells ◽

Survival Rates ◽

Mrna Species ◽

Germ Cell Differentiation ◽

Traditional Japanese Medicine ◽

Mrna Transcripts ◽

Specific Mrna

With the increase in survival rates of cancer patients in recent years, infertility caused by anticancer treatments has become a significant concern for cancer survivors. Some studies have suggested that Sertoli cells play a key role in mediating testicular immunology in busulfan-induced aspermatogenesis. We recently demonstrated that Gosha-jinki-gan (TJ107), a traditional Japanese medicine, can completely recover injured spermatogenesis in mice 60 days after busulfan injection. In the present study, we sought to examine the levels of mRNA transcripts encoding markers of 25 Sertoli cell-specific products and 10 markers of germ cell differentiation. Our results demonstrated that only supplementation of TJ107 at day 60 after busulfan injection could significantly recover the increase in five mRNA species (Amh, Clu, Shbg, Testin, and Il1a) and the decrease in four mRNA species (Aqp8, CST9, Wnt5a, and Tjp1) in response to Busulfan (BSF) at day 120, with the increase of all examined spermatogenic markers.

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Natural selection at the cellular level: insights from male germ cell differentiation

Cell Death and Differentiation ◽

10.1038/s41418-021-00812-0 ◽

2021 ◽

Author(s):

Daniel H. Nguyen ◽

Diana J. Laird

Keyword(s):

Natural Selection ◽

Cell Differentiation ◽

Germ Cell ◽

Cellular Level ◽

Male Germ Cell ◽

Germ Cell Differentiation

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Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization

Developmental Cell ◽

10.1016/j.devcel.2021.02.007 ◽

2021 ◽

Author(s):

Fabio M. D’Orazio ◽

Piotr J. Balwierz ◽

Ada Jimenez González ◽

Yixuan Guo ◽

Benjamín Hernández-Rodríguez ◽

...

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Germ Plasm ◽

Germ Cell Differentiation

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Clusters of Identical New Mutations Can Account for the “Overdispersed” Molecular Clock

Genetics ◽

10.1093/genetics/147.1.339 ◽

1997 ◽

Vol 147 (1) ◽

pp. 339-348 ◽

Cited By ~ 3

Author(s):

Haiying Huai ◽

R C Woodruff

Keyword(s):

Population Dynamics ◽

Cell Differentiation ◽

Germ Cell ◽

Molecular Clock ◽

Germ Cell Differentiation ◽

Multiple Copies ◽

Premeiotic Clusters ◽

T Values ◽

Independent Mutant ◽

New Mutations

Abstract Germ-cell mutations may occur during meiosis, giving rise to independent mutant gametes in a Poisson process, or before meiosis, giving rise to multiple copies of identical mutant gametes at a much higher probability than the Poisson expectation. We report that the occurrence of these early premeiotic clusters of new identical mutant alleles increases the variance-to-mean ratio of mutation rate (R(u) > 1). This leads to an expected variance-to-mean ratio (R(t)) of the molecular clock that is always greater than one and may cover the observed range of R(t) values. Hence, the molecular clock may not be overdispersed based on this new mutational model that includes clusters. To get a better estimation of R(u) and R(t), one needs measurements of the intrageneration variation of reproductive success (Ni/Ne(i)), population dynamics (k‒i), and the proportion of new mutations that occur in clusters (rc), especially those formed before germ-cell differentiation.

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