Nutrition affects Sertoli cell function but not Sertoli cell numbers in sexually mature male sheep

2016 ◽  
Vol 28 (8) ◽  
pp. 1152 ◽  
Author(s):  
Yongjuan Guan ◽  
Guanxiang Liang ◽  
Penny A. R. Hawken ◽  
Sarah J. Meachem ◽  
Irek A. Malecki ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Dietary Treatment ◽  
Cell Numbers ◽  
Under Nutrition ◽  
End Of Treatment ◽  
Effect Of Treatment ◽  
Sexually Mature ◽  
Male Sheep

We tested whether the reversible effects of nutrition on spermatogenesis in sexually mature sheep were mediated by Sertoli cells. Rams were fed with diets designed to achieve a 10% increase (High), no change (Maintenance) or a 10% decrease (Low) in body mass after 65 days. At the end of treatment, testes were lighter in the Low than the High group (P < 0.01). The Maintenance group had intermediate values that were not significantly different from those of the other two groups. Spermatogenesis (Johnsen score) was impaired in the Low group, but normal in both other groups. There was no effect of treatment on Sertoli cell numbers, although 1% of Sertoli cells appeared to retain their ability to proliferate. By contrast, Sertoli cell function was affected by dietary treatment, as evidenced by differences between the High and Low groups (P < 0.05) in the expression of seven Sertoli cell-specific genes. Under-nutrition appeared to reverse cellular differentiation leading to disruption of tight-junction morphology. In conclusion, in sexually mature sheep, reversible reductions in testis mass and spermatogenesis caused by under-nutrition were associated with impairment of basic aspects of Sertoli cell function but not with changes in the number of Sertoli cells.

Adult rat Sertoli cells secrete a factor or factors which modulate Leydig cell function

1987 ◽  
Vol 114 (3) ◽  
pp. 459-467 ◽  
Author(s):  
V. Papadopoulos ◽  
P. Kamtchouing ◽  
M. A. Drosdowsky ◽  
M. T. Hochereau de Reviers ◽  
S. Carreau
Keyword(s):  
Cyclic Amp ◽  
Sertoli Cell ◽  
Leydig Cell ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Function ◽  
Cell Interaction ◽  
Adult Rats ◽  
Adult Rat ◽  
Stimulating Factor

ABSTRACT Production of testosterone and oestradiol-17β by Leydig cells from adult rats was stimulated by LH or dibutyryl cyclic AMP (10 and 2·5-fold respectively). The addition of spent medium from normal, hemicastrated or γ-irradiated rat seminiferous tubule cultures, as well as from Sertoli cell cultures, to purified Leydig cells further enhanced both basal (44 and 53% for testosterone and oestradiol-17β respectively) and LH-stimulated (56 and 18%) steroid output. Simultaneously, a decrease (20–30%) in intracellular cyclic AMP levels was observed. This stimulating factor (or factors) secreted by the Sertoli cells is different from LHRH, is of proteinic nature and has a molecular weight ranging between 10 000 and 50 000; its synthesis is not controlled by FSH nor by testosterone. This factor(s) involved in rat Leydig cell steroidogenesis, at a step beyond the adenylate cyclase, does not require protein synthesis for testosterone formation whereas it does for oestradiol-17β production. It should be noted that a germ cell–Sertoli cell interaction modulates the synthesis of this factor(s). J. Endocr. (1987) 114, 459–467

Activin is produced by rat Sertoli cells in vitro and can act as an autocrine regulator of Sertoli cell function.

Endocrinology ◽  
1993 ◽  
Vol 132 (3) ◽  
pp. 975-982 ◽  
Author(s):  
J P de Winter ◽  
H M Vanderstichele ◽  
M A Timmerman ◽  
L J Blok ◽  
A P Themmen ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function

scholarly journals Rictor Regulates Spermatogenesis by Controlling Sertoli Cell Cytoskeletal Organization and Cell Polarity in the Mouse Testis

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4244-4256 ◽  
Author(s):  
Heling Dong ◽  
Zhenguo Chen ◽  
Caixia Wang ◽  
Zhi Xiong ◽  
Wanlu Zhao ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Regulatory Protein ◽  
Small Gtpase ◽  
Mutant Mice ◽  
Actin Dynamics ◽  
Testicular Development ◽  
Developmental Defects

Maintenance of cell polarity is essential for Sertoli cell and blood-testis barrier (BTB) function and spermatogenesis; however, the signaling mechanisms that regulate the integrity of the cytoskeleton and polarity of Sertoli cells are not fully understood. Here, we demonstrate that rapamycin-insensitive component of target of rapamycin (TOR) (Rictor), a core component of mechanistic TOR complex 2 (mTORC2), was expressed in the seminiferous epithelium during testicular development, and was down-regulated in a cadmium chloride-induced BTB damage model. We then conditionally deleted the Rictor gene in Sertoli cells and mutant mice exhibited azoospermia and were sterile as early as 3 months old. Further study revealed that Rictor may regulate actin organization via both mTORC2-dependent and mTORC2-independent mechanisms, in which the small GTPase, ras-related C3 botulinum toxin substrate 1, and phosphorylation of the actin filament regulatory protein, Paxillin, are involved, respectively. Loss of Rictor in Sertoli cells perturbed actin dynamics and caused microtubule disarrangement, both of which accumulatively disrupted Sertoli cell polarity and BTB integrity, accompanied by testicular developmental defects, spermiogenic arrest and excessive germ cell loss in mutant mice. Together, these findings establish the importance of Rictor/mTORC2 signaling in Sertoli cell function and spermatogenesis through the maintenance of Sertoli cell cytoskeletal dynamics, BTB integrity, and cell polarity.

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.

scholarly journals Stereological evaluation of Sertoli cell ontogeny during fetal and neonatal life in two diverse breeds of swine

2003 ◽  
Vol 178 (3) ◽  
pp. 395-403 ◽  
Author(s):  
SA McCoard ◽  
TH Wise ◽  
DD Lunstra ◽  
JJ Ford
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Prenatal Development ◽  
Late Gestation ◽  
Postnatal Life ◽  
Interstitial Tissue ◽  
Cell Numbers ◽  
Barrier Formation ◽  
Cell Population Growth ◽  
Testicular Size

Chinese Meishan (MS) boars have smaller testes due to fewer Sertoli cells compared with White Composite (WC) boars. The objective was to describe Sertoli cell development relative to circulating FSH concentrations in fetal and neonatal MS and WC boars. Testes and blood samples were collected on days 60, 75, 90 and 105 postcoitum (dpc) and 1, 7, 14 and 25 postpartum (dpp). One testis was immunostained for GATA4 or Ki67 antigen to evaluate total and proliferating Sertoli cell numbers respectively. Testicular size was greater (P<0.01) in WC than MS boars at all ages, associated with a greater mass of interstitial tIssue. Tubular mass (P<0.01) was greater in prenatal WC boars, but postnatally increased more rapidly (P<0.001) in MS boars, exceeding WC boars by 25 dpp. Sertoli cell numbers increased with age, was greater (P<0.001) in WC than MS boars during prenatal development but increased rapidly (P<0.01) by 1 dpp in MS and thereafter was similar in both breeds. The proportion of Ki67-positive Sertoli cells was maximal at 90 dpc, declining thereafter, did not differ between breeds through 7 dpp, but was greater (P<0.05) in WC than MS boars at 14 and 25 dpp. Plasma FSH concentrations were greater (P<0.05) in WC than MS boars at 75 dpc. FSH concentrations were elevated at 105 dpc (MS) and 1 dpp (WC) but declined thereafter with advancing postnatal age in both breeds. This study illustrates that late gestation represents the period of maximal Sertoli cell proliferation. Despite asynchronous Sertoli cell population growth between breeds during early postnatal life, differential mature Sertoli cell numbers and testicular size are probably due to differences in duration of the proliferative period after 25 dpp, potentially regulated by Sertoli cell maturation and blood-testis barrier formation. These events were not associated with fetal or early postnatal changes in FSH secretion.

scholarly journals Regulation of rat Sertoli cell function by FSH: possible role of phosphatidylinositol 3-kinase/protein kinase B pathway

2002 ◽  
Vol 174 (2) ◽  
pp. 195-204 ◽  
Author(s):  
SB Meroni ◽  
MF Riera ◽  
EH Pellizzari ◽  
SB Cigorraga
Keyword(s):  
Protein Kinase ◽  
Sertoli Cell ◽  
Mechanism Of Action ◽  
Sertoli Cells ◽  
Cell Function ◽  
Protein Kinase B ◽  
Lactate Production ◽  
Phosphatidylinositol 3 Kinase ◽  
Stimulation Of

The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K/PKB pathway in FSH regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. An increase in phosphorylated PKB (P-PKB) levels in response to FSH and dibutyryl-cAMP was observed. These increments in P-PKB levels were not observed in the presence of two PI3K inhibitors, wortmannin and Ly 294002. Inhibition of protein kinase A (PKA) by H89 did not decrease FSH stimulation of P-PKB levels. Taken together, these results indicate that FSH increases P-PKB levels in a PI3K-dependent and PKA-independent manner in rat Sertoli cells. In addition, wortmannin partially inhibited the ability of FSH to stimulate two well-known parameters of Sertoli cell function - transferrin secretion and lactate production - at doses equal to or lower than 0.1 microM. Related to lactate production, a decrease in FSH stimulation of lactate dehydrogenase activity and of basal and FSH-stimulated glucose uptake was observed in the presence of wortmannin. These metabolic changes were in most cases accompanied by changes in the levels of P-PKB. Altogether, these results suggest a meaningful role of the PI3K/PKB pathway in the mechanism of action of FSH in rat Sertoli cells.

scholarly journals Liver-regulating protein (LRP) is a plasma membrane protein involved in cell contact-mediated regulation of Sertoli cell function by primary spermatocytes

1995 ◽  
Vol 108 (3) ◽  
pp. 917-925
Author(s):  
N. Gerard ◽  
A. Corlu ◽  
B. Kneip ◽  
H. Kercret ◽  
M. Rissel ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Epithelial Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Cell Contact ◽  
Dependent Manner ◽  
Biliary Epithelial Cell

We have identified a liver-regulating protein involved in cell contact-mediated regulation of Sertoli cell function by primary spermatocytes in rat testis. Liver-regulating protein was studied using monoclonal antibody L8 prepared from rat primitive biliary epithelial cells. This molecule was located in vivo at the interface of Sertoli cells and spermatocytes, and expressed in a stage-dependent manner (expression peaked on leptotene-zygotene spermatocytes). In vitro, the liver-regulating protein was found on Sertoli cell, spermatocyte and early spermatid membranes. Immunoaffinity procedures revealed two peptides of 85 and 73 kDa for Sertoli cells, while spermatocytes and spermatids displayed a single smaller peptide of 56 kDa. The involvement of the liver-regulating protein in cell interaction-mediated regulation of Sertoli cell was assessed in vitro by tracing Sertoli cell transferrin and inhibin secretion, as well as mRNA synthesis in spermatocyte-Sertoli cell cocultures and in rat liver biliary epithelial cell-Sertoli cell cocultures, performed in the presence or absence of monoclonal antibody L8. Inhibition of the spermatocyte- and liver biliary epithelial cell-stimulated secretion of transferrin and inhibin by Sertoli cells was observed in the presence of antibody, whereas spermatocyte adhesiveness was unchanged. Using northern blot analysis, the steady state levels of transferrin mRNA decreased when the anti-liver-regulating protein antibody was added to the Sertoli cell-spermatocyte cocultures or to the Sertoli cell-liver biliary epithelial cell cocultures. The data demonstrate the role of the liver-regulating protein in cell-cell contact-mediated regulation of Sertoli function by primary spermatocytes and the important implications of this cell contact-dependent control in testicular activity.

Thyroid hormone affects the development of Sertoli cell function in the rat

1989 ◽  
Vol 123 (1) ◽  
pp. 105-111 ◽  
Author(s):  
S. Palmero ◽  
M. de Marchis ◽  
G. Gallo ◽  
E. Fugassa
Keyword(s):  
Thyroid Hormone ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Lactate Production ◽  
Postnatal Maturation ◽  
Cell Functions ◽  
Old Rats ◽  
Severe Retardation ◽  
Glutamyl Transpeptidase

ABSTRACT The relationship between thyroid activity and Sertoli cell function has been investigated in prepubertal rats. Male 28-day-old Wistar rats were used to prepare Sertoli cells by sequential enzyme digestion of the testes. Hypothyroidism, induced by oral administration of methimazole from the day of birth, was characterized by a severe retardation of body and testis growth and a net inhibition of the increase in Sertoli cell γ-glutamyl transpeptidase (GGT) activity as well as in androgen-binding protein (ABP) and lactate production, which normally occur during postnatal development of Sertoli cells. The functional parameters of Sertoli cells from hypothyroid 28-day-old rats approximated to those of cells from euthyroid 15-day-old animals. These results are consistent with the impairment of protein synthesis in Sertoli cells from hypothyroid rats compared with controls. Body and testis growth were improved and Sertoli cell functions were restored with 3,3′,5-tri-iodothyronine (T3) replacement therapy. An excess of T3 in the serum, induced by daily i.p. injections of T3 (100 μg/kg body wt) during the last week before the rats were killed, failed to induce changes in body and testis growth or in the activity of GGT and lactate dehydrogenase of Sertoli cells. Cells from hyperthyroid rats exhibited a specific decrease in ABP production. These results indicate that thyroid hormone is necessary for the postnatal maturation of Sertoli cell function and suggest a regulatory role of the hormone on gametogenic development in the prepubertal rat. Journal of Endocrinology (1989) 123, 105–111

scholarly journals Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Ingrid Sadler-Riggleman ◽  
Rachel Klukovich ◽  
Eric Nilsson ◽  
Daniel Beck ◽  
Yeming Xie ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Noncoding Rna ◽  
Cell Function ◽  
Sperm Concentration ◽  
Environmental Toxicants ◽  
Transgenerational Inheritance ◽  
Disease Etiology ◽  
General Decline

Abstract Male reproductive health has been in decline for decades with dropping sperm counts and increasing infertility, which has created a significant societal and economic burden. Between the 1970s and now, a general decline of over 50% in sperm concentration has been observed in the population. Environmental toxicant-induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome and transcriptome that are associated with the onset of testis disease. Gestating female F0 generation rats were transiently exposed during the period of fetal gonadal sex determination to the environmental toxicants, such as dichlorodiphenyltrichloroethane (DDT) or vinclozolin. The F1 generation offspring were bred (i.e. intercross within the lineage) to produce the F2 generation grand-offspring that were then bred to produce the transgenerational F3 generation (i.e. great-grand-offspring) with no sibling or cousin breeding used. The focus of the current study was to investigate the transgenerational testis disease etiology, so F3 generation rats were utilized. The DNA and RNA were obtained from purified Sertoli cells isolated from postnatal 20-day-old male testis of F3 generation rats. Transgenerational alterations in DNA methylation, noncoding RNA, and gene expression were observed in the Sertoli cells from vinclozolin and DDT lineages when compared to the control (vehicle exposed) lineage. Genes associated with abnormal Sertoli cell function and testis pathology were identified, and the transgenerational impacts of vinclozolin and DDT were determined. Alterations in critical gene pathways, such as the pyruvate metabolism pathway, were identified. Observations suggest that ancestral exposures to environmental toxicants promote the epigenetic transgenerational inheritance of Sertoli cell epigenetic and transcriptome alterations that associate with testis abnormalities. These epigenetic alterations appear to be critical factors in the developmental and generational origins of testis pathologies and male infertility.

scholarly journals UXT in Sertoli cells is required for blood–testis barrier integrity†

2020 ◽  
Vol 103 (4) ◽  
pp. 880-891
Author(s):  
Phillip A Thomas ◽  
Eric D Schafler ◽  
Sophie E Ruff ◽  
Maud Voisin ◽  
Susan Ha ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Structural Integrity ◽  
Cell Function ◽  
Somatic Tissue ◽  
Seminiferous Tubules ◽  
Testis Size ◽  
Conditional Deletion ◽  
Blood Testis Barrier

Abstract Spermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell’s ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood–testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT’s role in Sertoli cells and its contribution to the structural integrity of the BTB.

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