scholarly journals Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis

2002 ◽  
pp. 397-406 ◽  
Author(s):  
I Ketola ◽  
M Anttonen ◽  
T Vaskivuo ◽  
JS Tapanainen ◽  
J Toppari ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Sertoli Cells ◽  
Gonadal Development ◽  
Developmental Expression ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Adult Testis ◽  
Stage Specificity ◽  
And Function

OBJECTIVE: The transcription factors GATA-1 and GATA-4 have been implicated in the regulation of testicular development and function. Their cofactors FOG-1 and FOG-2 are expressed in the gonads, but their cell-specific and developmental expression in the testis remains unresolved. Therefore, we analyzed GATA-1, GATA-4, FOG-1 and FOG-2 expression in detail, from undifferentiated male urogenital ridge to adult testis. METHODS: Immunohistochemistry and in situ hybridization were applied on mouse testicular samples. RESULTS: GATA-4 and FOG-2, but not GATA-1 or FOG-1, were expressed as early as in the male urogenital ridge. FOG-2 expression was localized in the Sertoli cells at embryonal day 12.5 (E12.5), but it diminished with advancing fetal testicular development. In E17.5 testis, FOG-2 was present only in the testicular capsule and a subset of fetal Leydig cells. FOG-1 was expressed from E15.5 Sertoli cells onwards, whereas GATA-1 was not detected during the fetal period at all. In the postnatal testis, FOG-2 was abundantly expressed immediately after birth, but in adult testis its expression was predominantly restricted to stage VII-XII seminiferous tubules. Stage specificity was also found for FOG-1, which, similarly to GATA-1, was abundantly expressed in stage VII-XII tubules during adulthood. CONCLUSIONS: Our results indicate that FOG-2, in addition to GATA-4, has a role in early gonadal development and sexual differentiation, and FOG-1 at later fetal stages, while GATA-1 executes its action postnatally. The findings suggest that, in contrast to the hematopoietic system and the heart, GATA-1 and GATA-4 do not use FOG-1 and FOG-2 respectively as their only cofactors during the early stages of testicular development.

scholarly journals Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

2010 ◽  
Vol 162 (3) ◽  
pp. 625-631 ◽  
Author(s):  
Jonna Salonen ◽  
Ewa Rajpert-De Meyts ◽  
Susanna Mannisto ◽  
John E Nielsen ◽  
Niels Graem ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Germ Cell ◽  
Germ Cells ◽  
Target Genes ◽  
Developmental Expression ◽  
Human Testis ◽  
Testicular Development ◽  
Downstream Target ◽  
Germ Cell Differentiation

ObjectiveTesticular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms.MethodsFetal testis, testicular CIS, and overt tumor samples were analyzed by immunohistochemistry for GATA-4, GATA-6, FOG-2, steroidogenic factor 1 (NR5A1/SF1), anti-Müllerian hormone/Müllerian-inhibiting substance (AMH), and inhibin-α (INHα).ResultsGATA-4 was not expressed in normal germ cells, except for a subset of gonocytes at the 15th gestational week. The CIS cells expressed GATA-4 and GATA-6 heterogeneously, whereas most of the CIS cells expressed GATA-4 cofactor FOG-2. GATA target gene SF-1 was expressed heterogeneously in CIS cells, whereas INHα and AMH were mostly negative. Seminomas and yolk sac tumors were positive for GATA-4 and GATA-6, but mostly negative for FOG-2 and the GATA target genes. In contrast, pluripotent embryonal carcinomas and choriocarcinomas were GATA-4 and GATA-6 negative.ConclusionsDifferential expression of the GATA-4 target genes suggested cell-specific functions of GATA-4 in the germ and somatic cells. The GATA-4 expression in early fetal gonocytes, CIS, and seminoma cells but the absence in more mature germ cells is consistent with the early fetal origin of CIS cells and suggests that GATA-4 is involved in early germ cell differentiation.

scholarly journals TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-chi Shen ◽  
Adrienne Niederriter Shami ◽  
Lindsay Moritz ◽  
Hailey Larose ◽  
Gabriel L. Manske ◽  
...  
Keyword(s):  
Tissue Homeostasis ◽  
Testicular Development ◽  
Myoid Cells ◽  
Regenerative Capacity ◽  
Adult Testis ◽  
Mesenchymal Progenitors ◽  
And Function ◽  
Potential Reserve ◽  
Resident Fibroblast

AbstractTesticular development and function rely on interactions between somatic cells and the germline, but similar to other organs, regenerative capacity declines in aging and disease. Whether the adult testis maintains a reserve progenitor population remains uncertain. Here, we characterize a recently identified mouse testis interstitial population expressing the transcription factor Tcf21. We found that TCF21lin cells are bipotential somatic progenitors present in fetal testis and ovary, maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury. In vitro, TCF21lin cells are multipotent mesenchymal progenitors which form multiple somatic lineages including Leydig and myoid cells. Additionally, TCF21+ cells resemble resident fibroblast populations reported in other organs having roles in tissue homeostasis, fibrosis, and regeneration. Our findings reveal that the testis, like other organs, maintains multipotent mesenchymal progenitors that can be potentially leveraged in development of future therapies for hypoandrogenism and/or infertility.

scholarly journals Minireview: Transcriptional Regulation of Gonadal Development and Differentiation

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Types ◽  
Gonadal Development ◽  
Targeted Mutagenesis ◽  
Seminiferous Tubules ◽  
Molecular Pathways ◽  
Theca Cells ◽  
Main Cell

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.

Developmental expression of transforming growth factors alpha and beta in mouse fetus

1988 ◽  
Vol 8 (8) ◽  
pp. 3415-3422
Author(s):  
J N Wilcox ◽  
R Derynck
Keyword(s):  
Transforming Growth Factor ◽  
Developmental Expression ◽  
Otic Vesicle ◽  
Tgf Beta ◽  
Hematopoietic Organ ◽  
Mouse Fetus ◽  
Branchial Arches ◽  
Factor Alpha ◽  
And Function

Expression of mRNA for transforming growth factor alpha (TGF-alpha) and TGF-beta 1 during the fetal development of mice was evaluated by in situ hybridization. TGF-alpha mRNA was detected in 9- and 10-day fetuses but was absent in older fetuses. TGF-alpha mRNA-containing cells were found in the placenta, otic vesicle, oral cavity, pharyngeal pouch, first and second branchial arches, and developing kidneys. mRNA for TGF-beta 1 was present in hematopoietic cells of blood islands and capillaries and in the liver as it began to bud off on day 10 and function as a hematopoietic organ.

scholarly journals Bovine fetal testicular development in the Nellore breed

2017 ◽  
Vol 38 (4Supl1) ◽  
pp. 2551
Author(s):  
Juliana Stephany de Souza ◽  
Maria Carolina Villani Miguel ◽  
Marcos Antônio Maioli ◽  
Arthur Nelson Trali Neto ◽  
David Giraldo Arana ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Principal Component ◽  
Gonadal Development ◽  
Cell Number ◽  
Testicular Development ◽  
Testosterone Concentration ◽  
Testicular Weight ◽  
Bovine Fetuses

The study of gonadal development improves the understanding of factors that can influence the reproductive development process. This study aims to characterize bovine fetal testicular development and the testosterone level in the Nellore breed. For the study, 162 bovine fetuses aged between 3 and 8 months were collected from Nellore cows at a local abattoir. The fetal age was estimated by DP=8.4+0.087L+5.46?L, where DP is the estimated pregnancy day and L represents fetal length. The fetal gonadal weight (g), width (cm), and thickness (cm) were measured. Thereafter, the gonads were submitted to classic histology processes in 3-µm-thick slices cut at 210 µm intervals. The Sertoli cells, Leydig cells, and germ cells were counted. Blood samples were collected from umbilical cords for testosterone levels. The data were analyzed using the Spearman correlation test followed by Principal Component Analysis and one-way ANOVA to compare the averages between months. The testicular weight and volume were found to have a positive correlation with the numbers of Sertoli cells (r = 0.84; p < 0.0001 and r = 0.92; p < 0.0001, respectively), Leydig cells (r = 0.80; p < 0.0001 and r = 0.90; p < 0.0001, respectively), and germ cells (r = 0.84; p < 0.0001 and r = 0.93; p < 0.0001, respectively) and to be negatively correlated with testosterone plasmatic concentration (r = -0.31; p = 0.0001 and r = -0.22; p = 0.006, respectively) during pregnancy. After the fifth month, the numbers of Sertoli cells, Leydig cells and germ cells differed (p < 0.0001) from the following gestational months. The highest testosterone concentration (p = 0.007) was observed in the fifth month of gestation and was followed by a concentration decrease in the seventh and eighth months. The increase in cell quantity was responsible for the increase in testicular weight and volume during fetal development. On the other hand, the testosterone concentration followed the increase in testicular weight and volume until the 7th month of gestation and regressed during the 8th and 9th months, in addition to the increase in cell number.

70 GONADAL DEVELOPMENT IN GUINEA PIG MALES (CAVIA PORCELLUS)

2016 ◽  
Vol 28 (2) ◽  
pp. 164
Author(s):  
F. Oliveira ◽  
A. Santos ◽  
A. A. Neto
Keyword(s):  
Guinea Pig ◽  
Sertoli Cells ◽  
Sexual Differentiation ◽  
Primordial Germ Cells ◽  
Gonadal Development ◽  
Postnatal Period ◽  
Seminiferous Tubules ◽  
Morphological Description ◽  
Hormonal Function ◽  
Gonad Differentiation

Sexual differentiation in mammals is an event that presents many variations between species. Because it is related to hormonal function, any imbalance in the androgens and estrogens production can lead to malformations. Because sexual differentiation occurs in different ways among various animals, the recognition of their peculiarities becomes important in order to correct reproductive handling in different species. Considering that the guinea pig is commonly used as an experimental model in the reproductive area, the goal of this work was to perform a morphological description of gonad differentiation of the male guinea pig during embryonic development. In total, 11 conceptuses with ages 25 (n = 3), 30 (n = 2), 40 (n = 2), 50 (n = 2), and 65 (n = 2) days were used for light microscopy processing. The embryos at 25 days were processed completely. For the others, the gonads were dissected. The samples were dehydrated in alcohol, embedded in paraffin, and 5-µm sections were stained with hematoxylin-eosin. In the guinea pig gonad at 25 days gestation, there was a presence of gonadal cords, formed by condensation of somatic cells, which is characteristic of an undifferentiated gonad. In addition, we observed the presence of mesonephric and paramesonephric ducts in different embryos, indicating that other genital system organs were not formed. For the 30 days of development of guinea pigs, we observed that gonadal cords were differentiated in testicular cords by invasion of mesenchymal and endothelial cells, and also composed of Sertoli cells and primordial germ cells. These cords were among a large amount of testicular mesenchyme at the 40-day group. With 50- and 65-day development samples, the gonad was completely differentiated into testicle, with the presence of spermatogonia and Sertoli cells in the seminiferous tubules, and a large amount of interstitial Leydig cells around the tubules. We conclude that gonadal differentiation in guinea pig males occurs around the middle of pregnancy, between 25 and 30 days and that, before the end of the pregnancy, at 50 days, the testicle presents morphology similar to that found in the postnatal period.

scholarly journals Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Xenograft Model ◽  
Cell Maturation ◽  
Human Testis ◽  
Testicular Development ◽  
Future Fertility ◽  
And Function ◽  
Testis Tissue

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.

scholarly journals Assembly and Function of Gonad-Specific Non-Membranous Organelles in Drosophila piRNA Biogenesis

2019 ◽  
Vol 5 (4) ◽  
pp. 52 ◽  
Author(s):  
Shigeki Hirakata ◽  
Mikiko C. Siomi
Keyword(s):  
Dna Damage ◽  
Gonadal Development ◽  
Mitochondrial Membranes ◽  
Animal Life ◽  
Transposon Silencing ◽  
Dna Elements ◽  
Non Coding Rnas ◽  
And Function ◽  
Pirna Pathway

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that repress transposons in animal germlines. This protects the genome from the invasive DNA elements. piRNA pathway failures lead to DNA damage, gonadal development defects, and infertility. Thus, the piRNA pathway is indispensable for the continuation of animal life. piRNA-mediated transposon silencing occurs in both the nucleus and cytoplasm while piRNA biogenesis is a solely cytoplasmic event. piRNA production requires a number of proteins, the majority of which localize to non-membranous organelles that specifically appear in the gonads. Other piRNA factors are localized on outer mitochondrial membranes. In situ RNA hybridization experiments show that piRNA precursors are compartmentalized into other non-membranous organelles. In this review, we summarize recent findings about the function of these organelles in the Drosophila piRNA pathway by focusing on their assembly and function.

scholarly journals Ontogenetic Pattern of Thyroid Hormone Receptor Expression in the Human Testis

2000 ◽  
Vol 85 (9) ◽  
pp. 3453-3457 ◽  
Author(s):  
Emmanuele A. Jannini ◽  
Anna Crescenzi ◽  
Nadia Rucci ◽  
Emiliano Screponi ◽  
Eleonora Carosa ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Thyroid Hormone ◽  
Sertoli Cells ◽  
Pcr Amplification ◽  
Receptor Expression ◽  
Northern Analysis ◽  
Human Testis ◽  
Adult Testis ◽  
Maximal Expression

Abstract We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) α1 and α2 and β messenger RNA (mRNA) levels in normal human testicular tissue during development and in adulthood. Nonpathological specimens from five aborted fetuses (17 and 23 weeks of gestation, three and two cases, respectively) and from four patients undergoing orchiectomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyzed by Northern blot, semiquantitative RT-PCR amplification using DNA sequences or specifically designed primers for the TR isoforms, and in situ hybridization. By using PCR amplification, we found that TRα1 and TRα2 are both expressed at different levels in fetal and adult testis. At all ages TRα2 is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TRα2 and TRα1 in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TRα1 dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TRβ was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRβ either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TRβ and that TRα1 and TRα2 colocalized in Sertoli cells of prepubertal testis, whereas germ and interstitial cells appeared devoid of TR mRNA signals. From these results it can be concluded that the human testis exclusively expresses TRα, which is localized in Sertoli cells, TRβ being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TRα1 and TRα2. Theα 2/α1 ratio rises dramatically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal expression of T3 binding isoform TRα1, and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.

Effect of thyroid hormone on the pre- and post-natal development of the rat testis

1991 ◽  
Vol 129 (1) ◽  
pp. 35-NP ◽  
Author(s):  
S. Francavilla ◽  
G. Cordeschi ◽  
G. Properzi ◽  
L. Di Cicco ◽  
E. A. Jannini ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Serum Levels ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Postnatal Life ◽  
Fetal Life ◽  
Newborn Rats ◽  
Total Thyroxine ◽  
Delayed Maturation

ABSTRACT The relationship between thyroid function and testicular development in the rat was investigated. Hypothyroidism was induced during fetal or postnatal life by adding methimazole (MMI) to the drinking water of pregnant or lactating mothers. A group of newborn rats was treated with MMI and i.p. injections of l-tri-iodothyronine (l-T3). Hypothyroidism was shown by the reduced serum levels of total T3 and of total thyroxine (T4) in pregnant mothers and in pubertal rats. Testes were studied using light microscopy at 18 and 21 days post coitum or during puberty (21, 35 and 50 days after birth); serum levels of gonadotrophins were also evaluated in pubertal rats. Hypothyroidism had no effect on testicular development during fetal life and when induced in newborn rats it was associated at puberty with reduced serum levels of FSH and LH and with delayed maturation of the testis compared with control rats. The delay in maturation consisted of a reduction in the diameter of seminiferous tubules, and a reduction in the number of germ cells per tubule; this was associated with increased degeneration and arrested maturation of germ cells. In addition, Sertoli cells demonstrated retarded development, as indicated by a delay in the appearance of cytoplasmic lipids and in the development of a tubule lumen. Hormonal and morphological abnormalities were absent in rats treated with MMI plus l-T3. In conclusion, hypothyroidism occurring soon after birth caused reduced levels of gonadotrophins in the serum and a delay in pubertal spermatogenesis, possibly due to retarded differentiation of the Sertoli cells. Journal of Endocrinology (1991) 129, 35–42

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