300 IMMUNO-EXPRESSION OF POTENTIAL FACTORS REGULATING SERTOLI CELL PROLIFERATION IN THE PREPUBERTAL BOAR

2006 ◽  
Vol 18 (2) ◽  
pp. 257
Author(s):  
J. Baldrighi ◽  
W. Averhart ◽  
T. Phillips ◽  
K. Carnes ◽  
R. Hess ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Testis Size ◽  
Regulatory Factors ◽  
Time Points ◽  
Stage Of Development ◽  
Potential Factors ◽  
P27 Kip1

Today's pork production is very dependent on reproductive efficiency. Any improvements in the production capability (e.g., number of sperm produced) of the animals involved would be invaluable. Many researchers have examined methods to improve oocyte production, but have not focused on the concentration of sperm produced from a single boar used for artificial insemination (AI). The benefit of using AI is that a greater number of females can be bred to a single boar; thus the total amount of sperm per ejaculation is the main factor in the efficiency of AI. An increase in the number of Sertoli cells leads to an increase in testis size and the number of sperm produced because there are a finite number of germ cells that can be supported by the Sertoli cell during spermatogenesis. Therefore, by examining the factors that control the growth and differentiation of Sertoli cells, the amount of sperm per ejaculation in an individual boar can be increased. The purpose of this research is to begin a systematic analysis of cell cycle regulators expressed in the Sertoli cell during testicular development in the pig. By using pigs of different ages, we will establish a baseline of what regulatory factors are present at different time points in the developing Sertoli cell. Identification of certain factors could lead to an increase in sperm production by enabling the growth of Sertoli cells or inhibition of the natural reduction of these cells. Immunohistochemistry (IHC) analysis was performed on testis tissues from different males (n = 2) at various ages (3, 7, 14, 25, and 50 days) prior to puberty. Tissues were fixed in modified Davidson's fixative, embedded in paraffin, and sectioned; slides were processed for IHC. After antigen retrieval, endogenous hydrogen peroxidase was blocked with 0.6% H2O2 and sections were incubated overnight at 4°C with the appropriate antibody. The following antibodies were used to examine the factors controlling Sertoli cell proliferation: GATA-4 (transcription factor specific for developing and adult pig Sertoli cells), Ki67 (a nuclear protein present in all phases of the cell cycle except G0), cyclin-dependent kinase inhibitor p27 (Kip1), and steroid receptors AR (androgen receptor) and LH2 (estrogen receptor). The slides were then incubated with an appropriate secondary antibody, visualized with DAB chromagen, and counterstained with Mayer's hematoxylin. Immunostaining using p27 (Kip1) revealed no positive staining in any of the days tested, as there is cell division during all of these time points. Protein expression for Ki67 stained mildly after Day 25, suggesting that Sertoli cells became more active at this stage of development. The AR weakly stained and GATA-1 stained intensely at all time points. The data for LH2 were inconclusive and the procedure needs to be performed again. These experiments only give a glimpse of the regulatory factors involved in Sertoli cell proliferation in the developing boar testis. Further studies are being planned to explore other potential factors involved.

scholarly journals E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1691
Author(s):  
Rong-Ge Yan ◽  
Qi-Lin Yang ◽  
Qi-En Yang
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Conditional Knockout ◽  
Seminiferous Tubules ◽  
Quiescent State ◽  
Testis Size ◽  
Cell Fate Decisions

In the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty. Functional evidences suggest that the size of Sertoli cell population determines sperm production and fertility. However, factors that direct Sertoli cell proliferation and maturation are not fully understood. Transcription factor E4F1 is a multifunctional protein that serves essential roles in cell fate decisions and because it interacts with pRB, a master regulator of Sertoli cell function, we hypothesized that E4F1 may have a functional role in Sertoli cells. E4f1 mRNA was present in murine testis and immunohistochemical staining confirmed that E4F1 was enriched in mature Sertoli cells. We generated a conditional knockout mouse model using Amh-cre and E4f1flox/flox lines to study E4F1 fucntion in Sertoli cells and the results showed that E4f1 deletion caused a significant reduction in testis size and fertility. Further analyses revealed that meiosis progression and spermiogenesis were normal, however, Sertoli cell proliferation was impaired and germ cell apoptosis was elevated in the testis of E4f1 conditional knockout mice. On the basis of these findings, we concluded that E4F1 was expressed in murine Sertoli cells and served important functions in regulating Sertoli cell proliferation and fertility.

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

p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1581-1590 ◽  
Author(s):  
P. Chen ◽  
N. Segil
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Inner Ear ◽  
Hair Cells ◽  
Cellular Proliferation ◽  
Adult Life ◽  
Organ Of Corti ◽  
Morphological Development ◽  
Supporting Cells ◽  
P27 Kip1

Strict control of cellular proliferation is required to shape the complex structures of the developing embryo. The organ of Corti, the auditory neuroepithelium of the inner ear in mammals, consists of two types of terminally differentiated mechanosensory hair cells and at least four types of supporting cells arrayed precisely along the length of the spiral cochlea. In mice, the progenitors of greater than 80% of both hair cells and supporting cells undergo their terminal division between embryonic day 13 (E13) and E14. As in humans, these cells persist in a non-proliferative state throughout the adult life of the animal. Here we report that the correct timing of cell cycle withdrawal in the developing organ of Corti requires p27(Kip1), a cyclin-dependent kinase inhibitor that functions as an inhibitor of cell cycle progression. p27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells. In wild-type animals, p27(Kip1) expression is downregulated during subsequent hair cell differentiation, but it persists at high levels in differentiated supporting cells of the mature organ of Corti. In mice with a targeted deletion of the p27(Kip1) gene, proliferation of the sensory cell progenitors continues after E14, leading to the appearance of supernumerary hair cells and supporting cells. In the absence of p27(Kip1), mitotically active cells are still observed in the organ of Corti of postnatal day 6 animals, suggesting that the persistence of p27(Kip1) expression in mature supporting cells may contribute to the maintenance of quiescence in this tissue and, possibly, to its inability to regenerate. Homozygous mutant mice are severely hearing impaired. Thus, p27(Kip1) provides a link between developmental control of cell proliferation and the morphological development of the inner ear.

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.

Changes in histology, protein expression, and autophagy in dairy goat testes during non-breeding season

2021 ◽  
Author(s):  
Huaming Xi ◽  
Fa Ren ◽  
Yu Li ◽  
Yeqing Du ◽  
Liqiang Wang ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Breeding Season ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Semen Quality ◽  
Wilms Tumor ◽  
Dairy Goat ◽  
Testis Size ◽  
Seasonal Breeding ◽  
Dairy Goats

Abstract Seasonal reproduction contributes to increased chances of offspring survival in some animals. Dairy goats are seasonal breeding mammals. In this study, adult male Guanzhong dairy goats (10–12 months old) were used. Testis size, semen quality, hormone level, apoptosis of germ cells, and autophagy of Sertoli cells were analyzed in dairy goats during the breeding (October) and non-breeding (April) seasons. We found that, during the non-breeding season for dairy goats, semen quality, follicle-stimulating hormone (FSH) levels, and testosterone levels were reduced, and the number of apoptotic germ cells increased. The proliferation with decrease activity of germ cells in dairy goat during the non-breeding season was significantly affected. However, the testis size did not change seasonally. Interestingly, Sertoli cell autophagy was more active during the non-breeding season. The expression levels of FSH receptor (FSHR), wilms tumor 1 (WT1), androgen binding protein (ABP), glial cell derived neurotrophic factor (GDNF), and stem cell factor (SCF) decreased in dairy goats during the non-breeding season. In summary, our results indicate that spermatogenesis in dairy goats during the non-breeding season was not completely arrested. In addition, germ cell apoptosis and the morphology of Sertoli cells considerably changed in dairy goats during the non-breeding season. Sertoli cell autophagy is involved in the seasonal regulation of spermatogenesis in dairy goats. These findings provide key insights into the fertility and spermatogenesis of seasonal breeding animals.

Signal transduction pathways in FSH regulation of rat Sertoli cell proliferation

2012 ◽  
Vol 302 (8) ◽  
pp. E914-E923 ◽  
Author(s):  
María F. Riera ◽  
Mariana Regueira ◽  
María N. Galardo ◽  
Eliana H. Pellizzari ◽  
Silvina B. Meroni ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Kinase Inhibitors ◽  
Production Capacity ◽  
Signal Transduction Pathways ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Cell Mitogen

The final number of Sertoli cells reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH is the major Sertoli cell mitogen; however, little is known about the signal transduction pathways that regulate the proliferation of Sertoli cells. The hypothesis of this investigation was that FSH regulates proliferation through a PI3K/Akt/mTORC1 pathway, and additionally, AMPK-dependent mechanisms counteract FSH proliferative effects. The present study was performed in 8-day-old rat Sertoli cell cultures. The results presented herein show that FSH, in addition to increasing p-Akt, p-mTOR, and p-p70S6K levels, increases p-PRAS40 levels, probably contributing to improving mTORC1 signaling. Furthermore, the decrease in FSH-stimulated p-Akt, p-mTOR, p-p70S6K, and p-PRAS40 levels in the presence of wortmannin emphasizes the participation of PI3K in FSH signaling. Additionally, the inhibition of FSH-stimulated Sertoli cell proliferation by the effect of wortmannin and rapamycin point to the relevance of the PI3K/Akt/mTORC1 signaling pathway in the mitotic activity of FSH. On the other hand, by activating AMPK, several interesting observations were made. Activation of AMPK produced an increase in Raptor phosphorylation, a decrease in p70S6K phosphorylation, and a decrease in FSH-stimulated Sertoli cell proliferation. The decrease in FSH-stimulated cell proliferation was accompanied by an increased expression of the cyclin-dependent kinase inhibitors (CDKIs) p19INK4d, p21Cip1, and p27Kip1. In summary, it is concluded that FSH regulates Sertoli cell proliferation with the participation of a PI3K/Akt/mTORC1 pathway and that AMPK activation may be involved in the detention of proliferation by, at least in part, a decrease in mTORC1 signaling and an increase in CDKI expression.

Tri-iodothyronine directly affects rat Sertoli cell proliferation and differentiation

1995 ◽  
Vol 145 (2) ◽  
pp. 355-362 ◽  
Author(s):  
S Palmero ◽  
M Prati ◽  
F Bolla ◽  
E Fugassa
Keyword(s):  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Aromatase Activity ◽  
Functional Maturation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Old Rats

Abstract The addition of physiological concentrations (1 nm) of tri-iodothyronine (T3) to the culture medium of Sertoli cells from prepubertal (8-day-old) rats stimulated both protein synthesis (+55%) and lactate (+50%) production, while it inhibited DNA synthesis (−30/35%) and aromatase activity (−45/50%); insignificant T3-dependent effects were observed in cultured Sertoli cells from midpubertal (28-day-old) rats. These data suggest an age-dependent role for thyroid hormone in promoting and maintaining Sertoli cell differentiation at puberty; moreover, the hormone is involved in the regulation of Sertoli cell proliferation. The present study validates the role of Sertoli cells as a specific target for T3 action at the testis level; it also demonstrates the existence of an early and critical direct influence of thyroid hormone on Sertoli cell proliferation and functional maturation. Journal of Endocrinology (1995) 145, 355–362

scholarly journals The Molecular Mechanism of Sex Hormones on Sertoli Cell Development and Proliferation

2021 ◽  
Vol 12 ◽  
Author(s):  
Wasim Shah ◽  
Ranjha Khan ◽  
Basit Shah ◽  
Asad Khan ◽  
Sobia Dil ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sex Hormones ◽  
Sertoli Cells ◽  
Production Capacity ◽  
Cell Development ◽  
Seminiferous Tubules ◽  
Recent Advancement ◽  
Specific Number

Sustaining and maintaining the intricate process of spermatogenesis is liable upon hormones and growth factors acting through endocrine and paracrine pathways. The Sertoli cells (SCs) are the major somatic cells present in the seminiferous tubules and are considered to be the main regulators of spermatogenesis. As each Sertoli cell supports a specific number of germ cells, thus, the final number of Sertoli cells determines the sperm production capacity. Similarly, sex hormones are also major regulators of spermatogenesis and they can determine the proliferation of Sertoli cells. In the present review, we have critically and comprehensively discussed the role of sex hormones and some other factors that are involved in Sertoli cell proliferation, differentiation and maturation. Furthermore, we have also presented a model of Sertoli cell development based upon the recent advancement in the field of reproduction. Hence, our review article provides a general overview regarding the sex hormonal pathways governing Sertoli cell proliferation and development.

scholarly journals miR-499 promotes immature porcine Sertoli cell growth through the PI3K/AKT pathway by targeting the PTEN gene

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Hu Gao ◽  
Bin Chen ◽  
Hui Luo ◽  
Bo Weng ◽  
Xiangwei Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Pten Gene ◽  
Seminiferous Tubules ◽  
Akt Signaling Pathway

Sertoli cells are indispensable for normal spermatogenesis, and increasing evidence has shown that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and regulatory mechanisms of miRNAs in Sertoli cells of domestic animals have not been fully investigated. In the present study, we mainly investigated the regulatory roles of miR-499 in immature porcine Sertoli cells. The results showed that miR-499 was mainly located in the basement section of seminiferous tubules of prepubertal porcine testicular tissue. Overexpression of miR-499 promoted cell proliferation and inhibited apoptosis, whereas miR-499 inhibition resulted in the opposite effect. The PTEN gene was directly targeted by miR-499, and the expression of mRNA and protein was also negatively regulated by miR-499 in immature porcine Sertoli cells. siRNA-induced PTEN knockdown resulted in a similar effect as an overexpression of miR-499 and abolished the effects of miR-499 inhibition on immature porcine Sertoli cells. Moreover, both miR-499 overexpression and the PTEN knockdown activated the PI3K/AKT signaling pathway, whereas inhibition of the PI3K/AKT signaling pathway caused immature porcine Sertoli cell apoptosis and inhibited cell proliferation. Overall, miR-499 promotes proliferation and inhibits apoptosis in immature porcine Sertoli cells through the PI3K/AKT pathway by targeting the PTEN gene. This study provides novel insights into the effects of miR-499 in spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.

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