Follicle-Stimulating Hormone-Independent Functions of Primate Sertoli Cells: Potential Implications in the Diagnosis and Management of Male Infertility

Devi, Y. Sangeeta; Sarda, Kanchan; Stephen, Benjamin; Nagarajan, Priyadharsini; Majumdar, Subeer S.

doi:10.1210/jc.2005-2072

Cited by 24 publications

(30 citation statements)

References 45 publications

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“…Its renewal and functioning, which underlie spermatogenesis, require the expression and precise coordination of a multitude of genes in both SCs and germ cells. Dysfunction of such genetic factors is often associated with disturbed spermatogenesis and is suspected to be a frequent cause of male infertility (38). In our study, assessment of SC-related MTA2 expression in human pathological testis by immunohistochemistry demonstrated a clear cut attenuated level of this histone modifier in the SCs of patients with impaired or arrested spermatogenesis, indicating that MTA2 expression in SCs may be associated with human spermatogenic failure.…”

Section: Discussionsupporting

confidence: 52%

Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis

Zhang

Zhu

et al. 2012

Journal of Biological Chemistry

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Background: Desensitization of FSH response by down-regulation of FSHR transcription is critical for FSH action. Results: Chromatin modifier MTA2 participates in the down-regulation of FSHR transcription. Conclusion:The FSH/Ar/MTA2 cascade may serve as an indispensable negative feedback mechanism to modulate FSH transduction events in Sertoli cells. Significance: Our findings provide new insights into mechanisms by which FSH is deregulated in male infertile patients.

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Section: Discussionsupporting

confidence: 52%

Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis

Zhang

Zhu

et al. 2012

Journal of Biological Chemistry

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“…Primary cultures of Sc provide an excellent opportunity for investigating their ability to express various genes under endocrine (FSH and T together or alone) or paracrine control (Fix et al 2004;Walker and Cheng 2005;Devi et al 2006;Cheng et al 2007;Viswanathan et al 2009;Shupe et al 2011;Bhattacharya et al 2012;Mishra et al 2012). Such information provides vital clues for determining the role of Sc in regulating fertility in males.…”

Section: Resultsmentioning

confidence: 99%

“…Pulsatile and constant hormonal treatments of Sc culture were run in parallel and gene expression was evaluated at various time points. Since pre-pubertal rat Sc of around 18 ± 2 days of age are reported to be the most hormone-responsive in culture, as found by us earlier (Devi et al 2006;Bhattacharya et al 2012Bhattacharya et al , 2015b and others (Fix et al 2004;Cheng et al 2007;Viswanathan et al 2009;Shupe et al 2011), we used Sc from this age group of rats. FSH and T were used in combination to stimulate cultured Sc, thereby mimicking the in vivo condition.…”

Section: Resultsmentioning

confidence: 99%

“…Sc were isolated following the procedure originally reported by Welsh and Wiebe (1975) with minor modifications as previously described by us (Majumdar et al 1995;Devi et al 2006). Briefly, the testes were washed twice in Hanks' balanced salt solution (HBSS), decapsulated and minced by using a sterile blade.…”

Section: Isolation Of Scmentioning

confidence: 99%

“…The synergistic effect of FSH and T promotes the secretion of various growth factors and metabolites by Sc to support the initiation and maintenance of male germ cell (Gc) division and differentiation (Walker and Cheng 2005). In order to understand the role of Sc in the regulation of Gc maturation and fertility, neonatal, pubertal and adult Sc have been extensively studied upon their isolation from testes of rodent and primate species (Majumdar et al 1995(Majumdar et al , 1998Walker and Cheng 2005;Devi et al 2006;Bhattacharya et al 2012Bhattacharya et al , 2015a. However, Sc cultured from rats aged 18 ± 2 days are predominantly used for in vitro studies (Steinberger et al 1978;Shupe et al 2011;Matsushita et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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Advantages of pulsatile hormone treatment for assessing hormone-induced gene expression by cultured rat Sertoli cells

et al. 2016

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In response to various hormonal (follicle-stimulating hormone [FSH] and testosterone [T]) and biochemical inputs, testicular Sertoli cells (Sc) produce factors that regulate spermatogenesis. A number of FSH- and T-responsive Sc-specific genes, necessary for spermatogenesis, have been identified to date. However, the hormone-induced in vitro expression pattern of most of these genes is reported to be inconsistent at various time points in primary rat Sc cultures. As a matter of convenience, cultured Sc are constantly exposed to hormones for a few hours to days in the reported literature, although Sc are exposed to pulsatile FSH and T in vivo. The major aim of the present study is to evaluate the advantage, if any, of the in vitro administration of pulsatile hormone (FSH and T in combination) treatment on gene expression of cultured Sc as compared with that of constant hormone treatment. Pulsatile treatment (a 30-min hormonal exposure every 3 h) mimicking the in vivo condition reveals a more prominent effect of hormones in augmenting gene expression as compared with constant treatment. Our results indicate that the expressions of Stem cell factor (Scf, only responsive to FSH), Claudin11 (only responsive to T) and Transferrin (both FSH- and T-responsive) mRNAs are significantly higher at 12 h upon pulsatile treatment than upon constant hormonal treatment. Maximal expression of relevant genes because of pulsatile treatment with hormones suggests that this protocol provides a more suitable premise for assessing hormone-induced gene expression in isolated Sc than one involving constant exposure to hormones.

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Sertoli cell specific decline in NOR‐1 leads to germ cell apoptosis and reduced fertility

Shukla

Ganguli

Sharma

2018

J of Cellular Biochemistry

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The somatic component of seminiferous epithelium, the Sertoli cells (Sc) respond to Follicle stimulating hormone (FSH), and Testosterone (T) to produce factors which are necessary for germ cell (Gc) survival and differentiation. Infant Sc do not support spermatogenesis in spite of sufficient hormonal milieu, a situation similar to that found in male idiopathic infertility. Sc maturation during pubertal period involves expression of some genes which may be important for initiation of spermatogenesis. Analysis of differentially expressed genes, one by one, in infant and pubertal Sc might provide useful information about the regulation of spermatogenesis. DNA microarray based analysis of mRNA from 5-days (infant) and 12-days (pubertal) old rat Sc revealed increased expression of Nor-1 by pubertal Sc. NOR-1 is an orphan nuclear receptor involved in maintaining cellular homeostasis and disease. We generated transgenic mice using shRNA cloned under Pem (Rhox5) promoter which is activated at puberty in Sc. Such transgenic mice had reduced Nor-1 expression and increased Tgfβ1, Tgfβ3, and Smad3 expression. Moreover, an increase in β-catenin expression was observed in NOR-1 knockdown testes. High β-catenin in such transgenic mice was found to be associated with disruption of Sc maturation characterized by elevated expression of Anti Mullerian hormone, Cytokeratin 18, and Sox9. This disruption of Sc maturation resulted in Gc apoptosis. Such NOR-1 knockdown mice showed reduced sperm count and litter size. We report for the first time that NOR-1 plays a crucial role in regulating sperm count and male fertility.

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Follicle-Stimulating Hormone-Independent Functions of Primate Sertoli Cells: Potential Implications in the Diagnosis and Management of Male Infertility

Cited by 24 publications

References 45 publications

Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis

Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis

Advantages of pulsatile hormone treatment for assessing hormone-induced gene expression by cultured rat Sertoli cells

Sertoli cell specific decline in NOR‐1 leads to germ cell apoptosis and reduced fertility

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