Npat ‐dependent programmed Sertoli cell proliferation is indispensable for testis cord development and germ cell mitotic arrest

2019 ◽  
Vol 33 (8) ◽  
pp. 9075-9086 ◽  
Author(s):  
Xiaohua Jiang ◽  
Shi Yin ◽  
Suixing Fan ◽  
Jianqiang Bao ◽  
Yuying Jiao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Mitotic Arrest ◽  
Testis Cord

scholarly journals Testicular Somatic Cells, not Gonocytes, Are the Major Source of Functional Activin A during Testis Morphogenesis

Endocrinology ◽  
2011 ◽  
Vol 152 (11) ◽  
pp. 4358-4367 ◽  
Author(s):  
Denise R. Archambeault ◽  
Jessica Tomaszewski ◽  
Andrew J. Childs ◽  
Richard A. Anderson ◽  
Humphrey Hung-Chang Yao
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Somatic Cells ◽  
Activin A ◽  
Protein Product ◽  
Conditional Knockout ◽  
Seminiferous Tubules ◽  
Testis Size ◽  
Testis Development ◽  
Testis Cord

Proper development of the seminiferous tubules (or testis cords in embryos) is critical for male fertility. Sertoli cells, somatic components of the seminiferous tubules, serve as nurse cells to the male germline, and thus their numbers decide the quantity of sperm output in adulthood. We previously identified activin A, the protein product of the activin βA (Inhba) gene, as a key regulator of murine Sertoli cell proliferation and testis cord expansion during embryogenesis. Although our genetic studies implicated fetal Leydig cells as the primary producers of testicular activin A, gonocytes are another potential source. To investigate the relative contribution of gonocyte-derived activin A to testis morphogenesis, we compared testis development in the Inhba global knockout mouse, which lacks activin A production in all cells (including the gonocytes), and a steroidogenic factor 1 (Sf1)-specific conditional knockout model in which activin A expression in testicular somatic cells is disrupted but gonocyte expression of activin A remains intact. Surprisingly, testis development was comparable in these two models of activin A insufficiency, with similar reductions in Sertoli cell proliferation and minor differences in testis histology. Thus, our findings suggest activin A from male gonocytes is insufficient to promote Sertoli cell proliferation and testis cord expansion in the absence of somatic cell-derived activin A. Evaluation of adult male mice with fetal disruption of activin A revealed reduced testis size, lowered sperm production, altered testicular histology, and elevated plasma FSH levels, defects reminiscent of human cases of androgen-sufficient idiopathic oligozoospermia.

scholarly journals Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation

2005 ◽  
Vol 186 (3) ◽  
pp. 429-446 ◽  
Author(s):  
Sarah J Meachem ◽  
Saleela M Ruwanpura ◽  
Jessica Ziolkowski ◽  
Jacquelyn M Ague ◽  
Michael K Skinner ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Cathepsin L ◽  
Passive Immunisation ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
The Impact

The critical influence of follicle stimulating hormone (FSH) on male fertility relates both to its impact on Sertoli cell proliferation in perinatal life and to its influence on the synthesis of Sertoli cell-derived products essential for germ cell survival and function in the developing adult testis. The nature and timing of this shift of germ cells to their reliance on specific Sertoli cell-derived products are not defined. Based on existing data, it is apparent that the dominant function of FSH shifts between 9 and 18 day postpartum (dpp) during the first wave of spermatogenesis from driving Sertoli cell proliferation to support germ cells. To enable comprehensive analysis of the impact of acute in vivo FSH suppression on Sertoli and germ cell development, FSH was selectively suppressed in Sprague–Dawley rats by passive immunisation for 2 days and/or 4 days prior to testis collection at 3, 9 and 18 dpp. The 3 dpp samples displayed no measurable changes, while 4 days of FSH suppression decreased Sertoli cell proliferation and numbers in 9 dpp, but not 18 dpp, animals. In contrast, germ cell numbers were unaffected at 9 dpp but decreased at 18 dpp following FSH suppression, with a corresponding increase in germ cell apoptosis measured at 18 dpp. Sixty transcripts were measured as changed at 18 dpp in response to 4 days of FSH suppression, as assessed using Affymetrix microarrays. Some of these are known as Sertoli cell-derived FSH-responsive genes (e.g. StAR, cathepsin L, insulin-like growth factor binding protein-3), while others encode proteins involved in cell cycle and survival regulation (e.g. cyclin D1, scavenger receptor class B 1). These data demonstrate that FSH differentially affects Sertoli and germ cells in an age-dependent manner in vivo, promoting Sertoli cell mitosis at day 9, and supporting germ cell viability at day 18. This model has enabled identification of candidate genes that contribute to the FSH-mediated pathway by which Sertoli cells support germ cells.

Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice

1996 ◽  
Vol 151 (1) ◽  
pp. 37-48 ◽  
Author(s):  
J Singh ◽  
D J Handelsman
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Postnatal Life ◽  
Testis Size ◽  
Cell Numbers ◽  
Natural Time ◽  
Neonatal Administration

Abstract We previously demonstrated that androgens alone, in the complete absence of gonadotropins, initiated qualitatively complete spermatogenesis in hypogonadal (hpg) mice. Although germ cell to Sertoli cell ratios were normal in hpg mice with androgen-induced spermatogenesis, testicular size, Sertoli cell and germ cell numbers only reached 40% of those of non-hpg mice, and Sertoli cell numbers were unaffected by androgen treatment started at 21 days of age. We postulated that these observations were due to diminished gonadotropin-dependent Sertoli cell proliferation during perinatal life while the Sertoli cells still exhibited normal carrying capacity for mature germ cells. In order to test this hypothesis, we examined the effects of administering androgens and gonadotropins to hpg mice during the first 2 weeks of postnatal life when Sertoli cells normally continue to proliferate. The study end-points were Sertoli and germ cell numbers in hpg mice following induction of spermatogenesis by 8 weeks treatment with 1 cm subdermal silastic testosterone implants. Newborn pups (postnatal day 0–1) were injected s.c. with recombinant human FSH (rhFSH) (0·5 IU/20 μl) or saline once daily for 14 days, with or without a single dose of testosterone propionate (TP) (100 μg/20 μl arachis oil) or human chorionic gonadotropin (hCG) (1 IU/20 μl). Untreated hpg and phenotypically normal littermates were studied as concurrent controls. At 21 days of age, all treated weanling mice received a 1 cm silastic subdermal testosterone implant and, finally, 8 weeks after testosterone implantation, all mice were killed. As expected, qualitatively complete spermatogenesis was induced in all groups by testosterone despite undetectable circulating FSH levels. Exogenous rhFSH increased testis size by 43% (P<0·002) but a single neonatal dose of either TP or hCG reduced the FSH effect although neither TP nor hCG had any effect alone. In contrast, a single neonatal dose of TP or hCG increased final seminal vesicle size whereas FSH had no effect. FSH and TP treatment significantly increased absolute numbers of testicular spermatids compared with saline treatment, whereas hCG and TP significantly increased testicular sperm when expressed relative to testis size. Stereological evaluation of Sertoli and germ cell numbers demonstrated a rise in the absolute numbers of Sertoli and all germ cell populations induced by neonatal administration of hormones. When expressed per Sertoli cells the numbers of germ cells in the treated mice were between 85 and 90% of non-hpg controls. We conclude that exogenous FSH treatment during the first 2 weeks of postnatal life, coinciding with the natural time of Sertoli cell proliferation, increases Sertoli cell numbers and thereby the ultimate size of the mature testis and its germ cell production. Thus neonatal gonadotropin secretion may be a critical determinant of the sperm-producing capacity of the mature testis. In addition, neonatal exposure to androgens could be important for the imprinting of sex accessory organs in hpg mice, with the long-term effects of altering the sensitivity of the accessory organs to exogenous testosterone later in life. Journal of Endocrinology (1996) 151, 37–48

scholarly journals DDB1 Regulates Sertoli Cell Proliferation and Testis Cord Remodeling by TGFβ Pathway

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 974
Author(s):  
Wei Zheng ◽  
Jabeen Nazish ◽  
Fazal Wahab ◽  
Ranjha Khan ◽  
Xiaohua Jiang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Transforming Growth Factor ◽  
Seminiferous Tubules ◽  
Exact Nature ◽  
Genetic Ablation ◽  
Testis Cord ◽  
Tgfβ Pathway

Testis cords are the embryonic precursors of the seminiferous tubules. Development of testis cords is a key event during embryonic testicular morphogenesis and is regulated by multiple signaling molecules produced by Sertoli cells. However, the exact nature and the cascade of molecular events underlying testis cord development remain to be uncovered. In the current study, we explored the role of DNA damage binding protein 1 (DDB1) in Sertoli cells during mouse testis cord development. The genetic ablation of Ddb1 specifically in Sertoli cells resulted in the compromised Sertoli cell proliferation and disruption of testis cord remodeling in neonatal mice. This testicular dysgenesis persisted through adulthood, resulting in smaller testis and low sperm production. Mechanistically, we observed that the DDB1 degradation can stabilize SET domain-containing lysine methyltransferase 8 (SET8), which subsequently decreases the phosphorylation of SMAD2, an essential intracellular component of transforming growth factor beta (TGFβ) signaling. Taken together, our results suggest an essential role of Ddb1 in Sertoli cell proliferation and normal remodeling of testis cords via TGFβ pathway. To our knowledge, this is the first upstream regulators of TGFβ pathway in Sertoli cells, and therefore it furthers our understanding of testis cord development.

Development of Testis Cords and the Formation of Efferent Ducts in Xenopus laevis: Differences and Similarities with Other Vertebrates

2021 ◽  
pp. 1-14
Author(s):  
Yuanyuan Li ◽  
Jinbo Li ◽  
Man Cai ◽  
Zhanfen Qin
Keyword(s):  
Cell Proliferation ◽  
Xenopus Laevis ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Testis Development ◽  
Larval Stages ◽  
Efferent Ducts ◽  
Steroidogenic Cells ◽  
Testis Cord ◽  
Anterior Posterior

The knowledge of testis development in amphibians relative to amniotes remains limited. Here, we used Xenopus laevis to investigate the process of testis cord development. Morphological observations revealed the presence of segmental gonomeres consisting of medullary knots in male gonads at stages 52–53, with no distinct gonomeres in female gonads. Further observations showed that cell proliferation occurs at specific sites along the anterior-posterior axis of the future testis at stage 50, which contributes to the formation of medullary knots. At stage 53, adjacent gonomeres become close to each other, resulting in fusion; then (pre-)Sertoli cells aggregate and form primitive testis cords, which ultimately become testis cords when germ cells are present inside. The process of testis cord formation in X. laevis appears to be more complex than in amniotes. Strikingly, steroidogenic cells appear earlier than (pre-)Sertoli cells in differentiating testes of X. laevis, which differs from earlier differentiation of (pre-)Sertoli cells in amniotes. Importantly, we found that the mesonephros is connected to the testis gonomere at a specific site at early larval stages and that these connections become efferent ducts after metamorphosis, which challenges the previous concept that the mesonephric side and the gonadal side initially develop in isolation and then connect to each other in amphibians and amniotes.

Germ Cell-Sertoli Cell Interactions Studies of Cyclic Protein-2 in the Seminiferous Tubule

1989 ◽  
Vol 564 (1 Regulation of) ◽  
pp. 173-185 ◽  
Author(s):  
WILLIAM W. WRIGHT ◽  
SONYA D. ZABLUDOFF ◽  
MOIRA ERICKSON-LAWRENCE ◽  
ABDUL W. KARZAI
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Seminiferous Tubule ◽  
Cell Interactions
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