Talk:Testis Development

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Cite this page: Hill, M.A. (2024, March 28) Embryology Testis Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Testis_Development

2011

The biology of the desmosome-like junction a versatile anchoring junction and signal transducer in the seminiferous epithelium

Int Rev Cell Mol Biol. 2011;286:223-69.

Lie PP, Cheng CY, Mruk DD. Source Population Council, Center for Biomedical Research, New York, New York, USA. Abstract Mammalian spermatogenesis, a complex process that involves the movement of developing germ cells across the seminiferous epithelium, entails extensive restructuring of Sertoli-Sertoli and Sertoli-germ cell junctions. Presently, it is not entirely clear how zygotene spermatocytes gain entry into the adluminal compartment of the seminiferous epithelium, which is sealed off from the systemic circulation by the Sertoli cell component of the blood-testis barrier, without compromising barrier integrity. To begin to address this question, it is critical that we first have a good understanding of the biology and the regulation of different types of Sertoli-Sertoli and Sertoli-germ cell junctions in the testis. Supported by recent studies in the field, we discuss how crosstalk between different types of junctions contributes to their restructuring during germ cell movement across the blood-testis barrier. We place special emphasis on the emerging role of desmosome-like junctions as signal transducers during germ cell movement across the seminiferous epithelium.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 21199783 http://www.ncbi.nlm.nih.gov/pubmed/21199783


Prenatal testosterone and dihydrotestosterone exposure disrupts ovine testes development

Reproduction. 2011 Apr 14. [Epub ahead of print]

Bormann CL, Smith GD, Padmanabhan V, Lee TM. Source C Bormann, OB/GYN, University of Wisconsin, Madison, 53792, United States.

Abstract

Androgens play important roles during the first trimester of intrauterine life, coinciding with genital tract differentiation, during virilization and maintenance of secondary male characteristics and during initiation of spermatogenesis. Little is known about the impact of inappropriate exposure to excess androgens during fetal development on male sexual maturation and reproduction. The objectives of this study were to determine the effects of prenatal 5α-dihydrotestosterone (DHT) and testosterone treatment during ovine sexual differentiation on post-pubertal testicular formation and subsequent potential for fertility as assessed by epididymal sperm characteristics. Rams prenatally treated with testosterone exhibited increased testicular weight relative to age-matched controls (C) and prenatal DHT-treated rams (P<0.05), as well as elevated total and free testosterone concentrations compared to DHT-treated rams (P=0.07 and P<0.05, respectively). The percentage of progressively motile sperm from the epididymis was significantly reduced in prenatal DHT-treated but not testosterone-treated rams compared to C rams (P<0.05). The testosterone-treated rams had a greater number of germ cell layers than DHT-treated rams, but comparable to the controls. Prenatal testosterone-treated rams had significantly larger seminiferous tubule diameter, and lumen diameter compared to prenatal DHT-treated (P<0.05). Significantly more prenatal DHT- and testosterone-treated rams (P<0.05) had occluded tubule lumen than C rams. Findings from this study demonstrate that exposure to excess testosterone/DHT during male fetal sexual differentiation have differential effects on post-pubertal testicular size, seminiferous tubule size and function, sperm motility, and testosterone concentrations.

PMID: 21493716 http://www.ncbi.nlm.nih.gov/pubmed/21493716

2010

Hormonal regulation of male germ cell development

J Endocrinol. 2010 May;205(2):117-31. Epub 2010 Feb 9.

Ruwanpura SM, McLachlan RI, Meachem SJ. Source Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.

Abstract

Over the past five decades, intense research using various animal models, innovative technologies notably genetically modified mice and wider use of stereological methods, unique agents to modulate hormones, genomic and proteomic techniques, have identified the cellular sites of spermatogenesis, that are regulated by FSH and testosterone. It has been established that testosterone is essential for spermatogenesis, and also FSH plays a valuable role. Therefore understanding the basic mechanisms by which hormones govern germ cell progression are important steps towards improved understating of fertility regulation in health diseases.

Figure 4 A diagram summarizing the sites, cellular mechanisms, and molecular pathways underpinning gonadotrophin (FSH and testosterone (T)) actions on human spermatogenesis based on the findings from the literature (in black) and unsolved issues (in red). http://joe.endocrinology-journals.org/cgi/content/full/205/2/117/FIG4


PMID: 20144980 http://www.ncbi.nlm.nih.gov/pubmed/20144980

http://joe.endocrinology-journals.org/cgi/content/full/205/2/117

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: background to spermatogenesis, spermatogonia, and spermatocytes

Microsc Res Tech. 2010 Apr;73(4):241-78.

Hermo L, Pelletier RM, Cyr DG, Smith CE. Source Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada H3A 2B2. louis.hermo@mcgill.ca

Abstract

Spermatogenesis, a study of germ cell development, is a long, orderly, and well-defined process occurring in seminiferous tubules of the testis. It is a temporal event whereby undifferentiated spermatogonial germ cells evolve into maturing spermatozoa over a period of several weeks. Spermatogenesis is characterized by three specific functional phases: proliferation, meiosis, and differentiation, and it involves spermatogonia, spermatocytes, and spermatids. Germ cells at steps of development form various cellular associations or stages, with 6, 12, and 14 specific stages being identified in human, mouse, and rat, respectively. The stages evolve over time in a given area of the seminiferous tubule forming a cycle of the seminiferous epithelium that has a well-defined duration for a given species. In this part, we discuss the proliferation and meiotic phase whereby spermatogonia undergo several mitotic divisions to form spermatocytes that undergo two meiotic divisions to form haploid spermatids. In the rat, spermatogonia can be subdivided into several classes: stem cells (A(s)), proliferating cells (A(pr), A(al)), and differentiating cells (A(1)-A(4), In, B). They are dependent on a specific microenvironment (niche) contributed by Sertoli, myoid, and Leydig cells for proper development. Spermatogonia possess several surface markers whereby they can be identified from each other. During meiosis, spermatocytes undergo chromosomal pairing, synapsis, and genetic exchange as well as transforming into haploid cells following meiosis. The meiotic cells form specific structural entities such as the synaptonemal complex and sex body. Many genes involved in spermatogonial renewal and the meiotic process have been identified and shown to be essential for this event.

Copyright 2009 Wiley-Liss, Inc.

PMID: 19941293 http://www.ncbi.nlm.nih.gov/pubmed/19941293


Drug transporters, the blood-testis barrier, and spermatogenesis

J Endocrinol. 2011 Mar;208(3):207-23. Epub 2010 Dec 6.

Su L, Mruk DD, Cheng CY. Source The Mary M Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York 10065, USA.

Abstract

The blood-testis barrier (BTB), which is created by adjacent Sertoli cells near the basement membrane, serves as a 'gatekeeper' to prohibit harmful substances from reaching developing germ cells, most notably postmeiotic spermatids. The BTB also divides the seminiferous epithelium into the basal and adluminal (apical) compartment so that postmeiotic spermatid development, namely spermiogenesis, can take place in a specialized microenvironment in the apical compartment behind the BTB. The BTB also contributes, at least in part, to the immune privilege status of the testis, so that anti-sperm antibodies are not developed against antigens that are expressed transiently during spermatogenesis. Recent studies have shown that numerous drug transporters are expressed by Sertoli cells. However, many of these same drug transporters are also expressed by spermatogonia, spermatocytes, round spermatids, elongating spermatids, and elongated spermatids, suggesting that the developing germ cells are also able to selectively pump drugs 'in' and/or 'out' via influx or efflux pumps. We review herein the latest developments regarding the role of drug transporters in spermatogenesis. We also propose a model utilized by the testis to protect germ cell development from 'harmful' environmental toxicants and xenobiotics and/or from 'therapeutic' substances (e.g. anticancer drugs). We also discuss how drug transporters that are supposed to protect spermatogenesis can work against the testis in some instances. For example, when drugs (e.g. male contraceptives) that can perturb germ cell adhesion and/or maturation are actively pumped out of the testis or are prevented from entering the apical compartment, such as by efflux pumps.

PMID: 21134990

The evolutionary history of testicular externalization and the origin of the scrotum

J Biosci. 2010 Mar;35(1):27-37.

Kleisner K, Ivell R, Flegr J. Source Department of Philosophy and History of Science, Charles University, Vinicna 7, 128 44 Prague, Czech Republic. kleisner@seznam.cz

Abstract

This paper re-examines the evolution of the scrotum and testicular descent in the context of the recent phylogeny of mammals. The adaptive significance of testicular descent and scrotality is briefly discussed. We mapped four character states reflecting the position of testes and presence of scrotum onto recent mammalian phylogeny. Our results are interpreted as follows: as to the presence of testicondy in Monotremata and most of Atlantogenata, which represent the basal group of all eutherians, we argue that primary testicondy represents a plesiomorphic condition for Eutheria as well as for all mammals. This is in opposition to the previous hypothesis of Werdelin and Nilsonne that the scrotum may have evolved before the origin of mammals and then repeatedly disappeared in many groups including monotremes. We suggest that the scrotum evolved at least twice during the evolutionary history of mammals, within Marsupialia and Boreoeutheria, and has subsequently been lost by many groups; this trend is especially strong in Laurasiatheria. We suggest that the recent diversity in testicular position within mammals is the result of multiple selection pressures stemming from the need to provide conditions suitable for sperm development and storage, or to protect the male gonads from excessive physical and physiological disturbance.

PMID: 20413907 http://www.ncbi.nlm.nih.gov/pubmed/20413907

http://www.ias.ac.in/jbiosci/mar2010/27.pdf

2009

A deficiency of lunatic fringe is associated with cystic dilation of the rete testis

Reproduction. 2009 Jan;137(1):79-93. Epub 2008 Sep 18.

Hahn KL, Beres B, Rowton MJ, Skinner MK, Chang Y, Rawls A, Wilson-Rawls J. Source School of Life Sciences, Arizona State University, Tempe, Arizona 85287-4501, USA.

Abstract

Lunatic fringe belongs to a family of beta1-3 N-acetyltransferases that modulate the affinity of the Notch receptors for their ligands through the elongation of O-fucose moieties on their extracellular domain. A role for Notch signaling in vertebrate fertility has been predicted by the intricate expression of the Notch receptors and their ligands in the oocyte and granulosa cells of the ovary and the spermatozoa and Sertoli cells of the testis. It has been demonstrated that disruption of Notch signaling by inactivation of lunatic fringe led to infertility associated with pleiotropic defects in follicle development and meiotic maturation of oocytes. Lunatic fringe null males were found to be subfertile. Here, we report that gene expression data demonstrate that fringe and Notch signaling genes are expressed in the developing testis and the intratesticular ductal tract, predicting roles for this pathway during embryonic gonadogenesis and spermatogenesis. Spermatogenesis was not impaired in the majority of the lunatic fringe null males; however, spermatozoa were unilaterally absent in the epididymis of many mice. Histological and immunohistochemical analysis of these testes revealed the development of unilateral cystic dilation of the rete testis. Tracer dye experiments confirm a block in the connection between the rete testis and the efferent ducts. Further, the dye studies demonstrated that many lunatic fringe mutant males had partial blocks of the connection between the rete testis and the efferent ducts bilaterally.

PMID: 18801836

New insights into epididymal biology and function

Hum Reprod Update. 2009 Mar-Apr;15(2):213-27. Epub 2009 Jan 8.

Cornwall GA.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, 79430, USA. gail.cornwall@ttuhsc.edu Abstract BACKGROUND: The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions.

METHODS: A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included.

RESULTS: While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients.

CONCLUSIONS: Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

PMID: 19136456 http://www.ncbi.nlm.nih.gov/pubmed/19136456

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639084

Phenotypic plasticity of mouse spermatogonial stem cells

PLoS One. 2009 Nov 19;4(11):e7909.

Morimoto H, Kanatsu-Shinohara M, Takashima S, Chuma S, Nakatsuji N, Takehashi M, Shinohara T. Source Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Abstract

BACKGROUND: Spermatogonial stem cells (SSCs) continuously undergo self-renewal division to support spermatogenesis. SSCs are thought to have a fixed phenotype, and development of a germ cell transplantation technique facilitated their characterization and prospective isolation in a deterministic manner; however, our in vitro SSC culture experiments indicated heterogeneity of cultured cells and suggested that they might not follow deterministic fate commitment in vitro.

METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we report phenotypic plasticity of SSCs. Although c-kit tyrosine kinase receptor (Kit) is not expressed in SSCs in vivo, it was upregulated when SSCs were cultured on laminin in vitro. Both Kit(-) and Kit(+) cells in culture showed comparable levels of SSC activity after germ cell transplantation. Unlike differentiating spermatogonia that depend on Kit for survival and proliferation, Kit expressed on SSCs did not play any role in SSC self-renewal. Moreover, Kit expression on SSCs changed dynamically once proliferation began after germ cell transplantation in vivo.

CONCLUSIONS/SIGNIFICANCE: These results indicate that SSCs can change their phenotype according to their microenvironment and stochastically express Kit. Our results also suggest that activated and non-activated SSCs show distinct phenotypes.

PMID: 19936070 http://www.ncbi.nlm.nih.gov/pubmed/19936070

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007909

Background reading

  • Aging of the human ovary and testis. Perheentupa A, Huhtaniemi I. Mol Cell Endocrinol. 2009 Feb 5;299(1):2-13. Epub 2008 Nov 18. Review. PMID: 19059459
  • Epithelial-mesenchymal crosstalk in Wolffian duct and fetal testis cord development. Archambeault DR, Tomaszewski J, Joseph A, Hinton BT, Yao HH. Genesis. 2009 Jan;47(1):40-8. Review. PMID: 18979542
  • Mixed signals: development of the testis. Cool J, Capel B. Semin Reprod Med. 2009 Jan;27(1):5-13. Epub 2009 Feb 5. Review. PMID: 19197800


2000

The testicular descent in human. Origin, development and fate of the gubernaculum Hunteri, processus vaginalis peritonei, and gonadal ligaments

Adv Anat Embryol Cell Biol. 2000;156:III-X, 1-98.

Barteczko KJ, Jacob MI.

Abteilung für Anatomie und Embryologie, Ruhr-Universität Bochum, Germany. klaus.barteczko@ruhr-uni-bochum.de


Testicular descent has to be divided into the turn-out of the testis and epididymis from the abdomen proper and an inner abdominal descent of genital organs. Both events are closely related to and depend on the development and reorganisation of ligaments, mainly the gubernaculum Hunteri. These seemingly unambiguous events are controversially described since the first description of the gubernaculum, and results and specifics of other species were intermingled with data from humans, thus giving more confusion than lucidity in this important step of gonadal development. Here, we concentrate on human embryos, chronologically investigated by serial sections, scanning electron microscopy, three-dimensional reconstructions, microdissection and immunohistochemistry. The first question to be answered was whether a real inner descent of gonads occurs. We demonstrated this inner descent by showing the relations of the gonads, mesonephros, cranial mesonephric ligament and the anlage of the diaphragm with the vertebral segments. No explosion-like increase in certain vertebral segments was observed which might simulate a gonadal descent. The inner descent is coupled with the growth of the gonad (ovary or testis), the involution of mesonephros, the descending septum transversum or the anlage of the diaphragm, and the intercalated cranial mesonephric ligament. This ligament always inserts medially at the border between the gonad and mesonephros in close relationship to the abdominal ostium of the müllerian duct, a region where hydatides often occur. In contrast to the testes, the ovaries arrive very early--20-25 mm CRL--at their definitive position of S2/3 (level of linea terminalis pelvis), yet, are transversally oriented. The cranial gonadal ligament does not exhibit notable increase in length during inner descent. It does not contain blood vessels. While regressing in both sexes, it will be replaced by the plica formed by the ovarian vessels, that is the suspensorium ligament of the ovary as known in adults. The second point to be investigated was the origin, development, structure and fate of the gubernaculum Hunteri as well as the processus vaginalis peritonei. Their arrangement and composition is crucial for testicular descent. We discriminated five phases of their development and differentiation. Phase I characterises the early development of the gubernaculum of stage 14 CC (5-7 mm CRL) embryos. It arises as conus inguinalis and connects the abdominal wall lateral to the umbilical artery with the caudal part of the mesonephric fold. It is in this early stage that the localisation of the inner inguinal ring is defined. In phase II, stage 20-23 CC (21-30 mm CRL), three parts of the gubernaculum--abdominal, interstitial and subcutaneous--can be distinguished. The processus vaginalis peritonei appears with its dorsal layer firmly adhering to the ventral side of the gubernaculum. The gubernaculum inserts cranially into the mesenchyme of the genital ducts at their crossing-over. Opposite to it, but at some distance, a ligament connects the caudal pole of the testis with the dorsal mesenchyme of the genital ducts. In female embryos, the analge of the ovarian ligament appears as a U-shaped, double peritoneal fold. Phase II is subdivided in phase IIa (32-55 mm CRL), characterised by an enormous increase in length and volume of the gubernaculum and also an enlargement of the processus vaginalis peritonei. In phase III, sex-specific differences in gonadal position and gubernacular structure can be observed for the first time. Testes increase in volume and come close to the mesenchyme of the genital ducts. The caudal pole of the testis overlaps both ducts. We also subdivide this phase into phase IIIa (about 100 mm CRL) where two very important events occur in male foetuses: 1, the swelling of the gubernaculum, and 2, the gliding of the testis across the genital ducts. This gliding is permitted by both, the regression of the müllerian duct and t

PMID: 11008363 http://www.ncbi.nlm.nih.gov/pubmed/11008363

Posttesticular development of spermatozoa of the tammar wallaby (Macropus eugenii)

J Anat. 1997 Feb;190 ( Pt 2):275-88.

Setiadi D, Lin M, Rodger JC. Department of Biological Sciences, University of Newcastle, NSW, Australia.

Abstract Tammar wallaby spermatozoa undergo maturation during transit through the epididymis. This maturation differs from that seen in eutherian mammals because in addition to biochemical and functional maturation there are also major changes in morphology, in particular formation of the condensed acrosome and reorientation of the sperm head and tail. Of spermatozoa released from the testes, 83% had a large immature acrosome. By the time spermatozoa reached the proximal cauda epididymis 100% of sperm had condensed acrosomes. Similarly 86% of testicular spermatozoa had immature thumb tack or T shape head-tail orientation while only 2% retained this immature morphology in the corpus epididymis. This maturation is very similar to that reported for the common brush tail possum, Trichosurus vulpecula. However, morphological maturation occurred earlier in epididymal transit in the tammar wallaby. By the time spermatozoa had reached the proximal cauda epididymis no spermatozoa had an immature acrosome and thumbtack orientation. Associated with acrosomal maturation was an increase in acrosomal thiols and the formation of disulphides which presumably account for the unusual stability of the wallaby sperm acrosome. The development of motility and progressive motility of tammar wallaby spermatozoa is similar to that of other marsupials and eutherian mammals. Spermatozoa are immotile in the testes and the percentage of motile spermatozoa and the strength of their motility increases during epididymal transit. During passage through the caput and corpus epididymis, spermatozoa first became weakly motile in the proximal caput and then increasingly progressively motile through the corpus epididymis. Tammar wallaby spermatozoa collected from the proximal cauda epididymis had motility not different from ejaculated spermatozoa. Ultrastructural studies indicated that acrosomal condensation involved a complex infolding of the immature acrosome. At spermiation the acrosome of tammar wallaby spermatozoa was a relatively large flat or concave disc which projected laterally and anteriorly beyond the limits of the nucleus. During transit of the epididymal caput and proximal corpus the lateral projections folded inwards to form a cup like structure the sides of which eventually met and fused. The cavity produced by this fusion was lost as the acrosome condensed to its mature form as a small button-like structure contained within the depression on the anterior end of the nucleus. During this process the dorsal surface of the immature acrosome and its outer acrosomal membrane and overlying plasma membrane were engulfed into the acrosomal matrix. This means that the dorsal surface of the acrosomal region of the testicular tammar wallaby sperm head is a transient structure. The dorsal acrosomal surface of the mature spermatozoon appears ultrastructurally to be the relocated ventral surface of the acrosomal projections which previously extended out beyond the acrosomal depression on the dorsal surface of the nucleus of the immature spermatozoon. PMID: 9061449