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PubMed2005

Testicular development, ultrasonographic and histological appearance of the testis in ram lambs immunized against recombinant LHRH fusion proteins.

Sixteen native ram lambs weaned at 10 wk of age were divided into two groups. Eight animals were immunized against LHRH with a mixture of two fusion proteins: ovalbumin-LHRH-7 and thioredoxin-LHRH-7. The immunized lambs received a primary immunization plus two booster immunizations at 4 and 12 wks. Animals in the control group (n=8) were not treated. Scrotal measurements and blood samples were taken at 2-week intervals. Beginning at 25 wk of age, semen was collected and sexual behaviour was evaluated on a weekly basis. At 35 and 37 wk of age testes and accessory glands of all animals were subjected to ultrasound scanning. At 37 wk of age animals were slaughtered and testes were evaluated histologically. Serum LHRH antibodies (P<0.01) were detected in animals of the immunized group which had reduced serum testosterone concentrations (P<0.01). Testicular development was suppressed in the immunized animals (P<0.01). Immunized animals exhibited mounting activity 5 wks later than control animals. No mature spermatozoa containing ejaculates were collected from immunized animals. Control animals had moderately echogenic ultrasonographic appearance at 37 wk age, whereas immunized animals had hypoechogenic images. Mean seminiferous tubule diameter in immunized lambs was significantly smaller than that in control lambs. Basal membrane was thickened and hyalinized; there was an increase in peritubular connective tissue. No proliferating spermatogonia or mature spermatozoa were present in the tubules in these animals. There were no differences in the ultrasonographic appearance of prostate and vesicular gland between control and immunized animals. The LHRH recombinant fusion proteins were effective in immunological castration in ram lambs when started at 10 wk of age as noted by differences in serum testosterone, testicular histology and ultrasonographic appearance of testis and weight of accessory sex glands. Determining the effects of immunization on ultrasonographic appearance of the testis related to time after immunization requires further investigations.

Aging↗
PubMed2001

Stage-dependent and alternative splicing of sGnRH messengers in rainbow trout testis during spermatogenesis.

The gonadotropin releasing hormone (GnRH) has long been considered as a neuropeptide involved in the control of the reproductive cycle. However, the presence of GnRH and its receptors in various tissues, including ovary and testis, suggests a role as autocrine/paracrine factor. In the present study, we report the expression of the sGnRH-1 and sGnRH-2 genes encoding salmon GnRH in rainbow trout testis throughout testicular development and spermatogenesis. We demonstrate that both sGnRH mRNA are expressed prior of sexual differentiation. In adult, northern blot analysis indicates that sGnRH-2 transcripts are expressed in the testis at higher levels than sGnRH-1 messengers. Moreover, we observed that the expression of sGnRH-2, and not sGnRH-1, messengers was stage-dependent. sGnRH-2 mRNA expression decreases at the onset and progressively rebounds at the end of spermatogenesis. In addition, we demonstrate that a complex stage-dependent and differential splicing of the sGnRH-2 messengers occurs throughout spermatogenesis. We isolated five transcripts corresponding to sGnRH-2 messengers. Two of them may encode a novel and shortened GnRH-associated peptide containing 18 residues instead of 46. Our data provide new insight in the putative role of GnRH and GAP peptides as autocrine/paracrine factors of spermatogenesis.

Alternative Splicing↗
PubMed2006

The pineal gland, but not melatonin, is associated with the termination of seasonal testicular activity in an annual reproductive cycle in roseringed parakeet Psittacula krameri.

The role of the pineal gland and its hormone melatonin in the regulation of annual testicular events was investigated for the first time in a psittacine bird, the roseringed parakeet (Psittacula krameri). Accordingly, the testicular responsiveness of the birds was evaluated following surgical pinealectomy with or without the exogenous administration of melatonin and the experimental manipulations of the endogenous levels of melatonin through exposing the birds to continuous illumination. An identical schedule was followed during the four reproductive phases, each characterizing a distinct testicular status in the annual cycle, namely, the phases of gametogenic quiescence (preparatory phase), seasonal recovery of gametogenesis (progressive phase), seasonal initiation of sperm formation (pre-breeding phase), and peak gametogenic activity (breeding phase). In each reproductive phase, the birds were subjected to various experimental conditions, and the effects were studied comparing the testicular conditions in the respective control birds. The study included germ cell profiles of the seminiferous tubules, the activities of steroidogenic enzymes 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and Delta(5)3beta-hydroxysteroid dehydrogenase (Delta(5)3beta- HSD) in the testis, and the serum levels of testosterone and melatonin. An analysis of the data reveals that the pineal gland and its hormone melatonin may play an inhibitory role in the development of the testis until the attainment of the seasonal peak in the annual reproductive cycle. However, in all probability, the termination of the seasonal activity of the testis or the initiation of testicular regression in the annual reproductive cycle appears to be the function of the pineal gland, but not of melatonin.

Animals↗
PubMedDate not supplied

Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha-null mice.

The peroxisome proliferator-activated receptor alpha (PPAR alpha) is the mediator of the biological effects of peroxisome proliferators through control of gene transcription. To determine if the toxic effects of di(2-ethylhexyl)phthalate (DEHP) are mediated by PPAR alpha, we examined its effect in PPAR alpha-null mice. Male Sv/129 mice, PPAR alpha-null (-/-) or wild-type (+/+) were fed ad libitum either a control diet or one containing 12,000 ppm DEHP for up to 24 wk. Significant body weight loss and high mortality was observed in (+/+) mice fed DEHP. By 16 wk, all DEHP-fed (+/+) mice had died of cystic renal tubular disease. In contrast, the (-/-) mice fed DEHP had no changes in body weight until later in the study nor increased mortality. Histologically, (+/+) mice fed DEHP had typical toxic lesions in liver, kidney, and testis while (-/-) mice fed DEHP had no toxic liver lesions but did show evidence of toxicity in kidney and testis after 4-8 wk of feeding, which progressed into moderate lesions by 24 wk. Analysis of hepatic and renal mRNAs showed a typical pleiotropic response in gene expression in the DEHP-fed (+/+) mice that was absent in the DEHP-fed (-/-) mice. These results provide evidence that PPAR alpha mediates the subacute-chronic toxicity of DEHP in liver, kidney, and testis. However, because (-/-) mice did develop toxic lesions in kidney and testis, DEHP can also act through PPAR alpha-independent pathways in mediating renal and testicular toxicity.

Animals↗
PubMed2005

Interactions among IQGAP1, Cdc42, and the cadherin/catenin protein complex regulate Sertoli-germ cell adherens junction dynamics in the testis.

The movement of developing germ cells across the seminiferous epithelium during spermatogenesis involves extensive adherens junction (AJ) restructuring between Sertoli cells, as well as between Sertoli and germ cells. In this report, we show that the intricate interactions between Cdc42 (a Rho family protein of Mr approximately 23 kDa originally identified in membranes of human platelets and placenta, and is the homolog of CDC42Sc, which is known to regulate of bud-site assembly in Saccharomyces cerevisiae) and its effector, IQ motif containing GTPase activating protein (IQGAP1, Mr approximately 189 kDa, it is also an actin-binding protein known to interact with Cdc42 and Rac1 GTPases), regulate Sertoli-germ cell, but not Sertoli-Sertoli cell, AJ dynamics. Using testis lysates for immunoprecipitation (IP), IQGAP1 was shown to associate with E-cadherin, N-cadherin, and beta-catenin (but not beta1-integrin and nectin-2), as well as with actin and vimentin (but not alpha-tubulin). Moreover, IQGAP1 was found to localize to the periphery of both Sertoli and germ cells in the seminiferous epithelium, at sites of cell-cell contacts. Using fluorescent microscopy with dual fluorescent probes, IQGAP1 was found to co-localize, at least in part, with N-cadherin in the seminiferous epithelium consistent with their localization at the basal and apical ES. Using Sertoli-germ cell cocultures, it was demonstrated that AJ assembly associated with a transient induction of Cdc42 and IQGAP1, which was not found when Sertoli cells were cultured alone. Lastly, a shift in the interactions of Cdc42, IQGAP1, beta-catenin, and N-cadherin was detected in Sertoli-germ cell cocultures using an Ca2+-induced AJ disruption model, which was used to examine AJ disassembly and its reassembly. In the presence of Ca2+, IQGAP1 bound preferentially to Cdc42 rather than to beta-catenin. However, when Ca2+ was depleted from cocultures using EGTA, a Ca2+ chelating agent, IQGAP1 lost its affinity for Cdc42 and became tightly associated with beta-catenin, destabilizing cadherin-mediated AJs between Sertoli and germ cells. Yet this shift of protein-protein interaction was not detected in Sertoli cells cultured alone. These results illustrate that the interactions among IQGAP1, Cdc42, and beta-catenin are crucial to the regulation of Sertoli-germ cell, but not Sertoli-Sertoli cell, AJ dynamics in the seminiferous epithelium.

Adherens Junctions↗
PubMedDate not supplied

Molecular events leading to fertilization--a review.

Fertilization consists of a sequence of complex events which culminates in the fusion of the genetic information provided by two parent cells, thus leading to the formation of a new individuum. The male gamete develops in the testis, acquires forward motility and fertilizing capacity during maturation in the epididymis, and after capacitation undergoes the acrosome reaction in the female reproductive tract. The female gamete matures in the cyclically developing follicles and, by the time of ovulation, reaches a quiescent stage at metaphase II of meiosis. Gamete fusion occurs in the distal tube, and involves a series of modifications on the egg surface and its investments, intended to protect the developing embryo from polyspermy.

Acrosome↗
PubMed1975

Hormonal regulation of isoenzymes of N-acetyl-beta-glucosaminidase and beta-galactosidase during spermatogenesis in the rat.

Isoenzymes of beta-galactosidase and of N-acetyl-beta-glucosaminidase were assayed during development of rat testis and as a function of hormonal treatments. Isoenzyme 1 of beta-galactosidase was highest in specific activity in the 4-day-old testis, at a point when Sertoli cells and gonocytes were the predominant cell type. Beta-galactosidase II, previously shown to be associated with the sperm acrosome, was undetectable through the spermatocyte stage of development, but increased in specific activity during the formation of spermatids. The specific activities of isoenzymes I and II of N-acetyl-beta-glucosaminidase increased markedly in association with the formation of spermatogonia and spermatocytes, and then declined with the appearance of spermatids. Following hypophysectomy of rats at 26 days of age or in adulthood the specific activities of the lysosomal enzymes beta-galactosidase I and N-acetyl-beta-glucosaminidase I and II increased markedly, while the acrosomal beta-galactosidase II was undetectable. The normal patterns of isoenzyme distributed were restored completely by administration of LH and FSH or testosterone to hypophysectomized animals. These results thus demonstrate specific patterns of isoenzyme concentration during spermatogenesis. Formation of the acrosome in developing spermatids is associated with the induction of new forms of beta-galactosidase (isoenzyme II) and N-acetyl-beta-glucosaminidase (sperm isoenzyme). These molecules appear to be specialized forms which may participate in fertilization, and their induction is dependent upon the actions of gonadotropins or testosterone.

Animals↗
PubMed2004

Novel testis-expressed profilin IV associated with acrosome biogenesis and spermatid elongation.

A novel profilin, named profilin IV, was cloned and characterized as a testicular isoform, distinct from the previously described testis-specific profilin III. Profilin IV showed only 30% amino acid identity with the other mammalian profilins; nevertheless, database searches produced significant alignments with the conserved profilin domain. Northern blot analysis and in situ transcript hybridization suggested that profilin IV, like profilin III, is transcribed in the germ cells. However, the timing of their expression during post-natal development of rat testis and in the rat spermatogenetic cycle was distinct. In the human testis, profilin IV mRNA expression correlates with the presence of germ cells suggesting that it may be a suitable molecular diagnostic parameter to supplement conventional histopathological diagnostics in the assessment of testicular biopsies. The predicted profilin IV protein was verified employing an anti-oligopeptide antibody. Western blot analysis detected an immunorelated testicular protein of approximately 14 kDa. Immunohistochemistry revealed an intracellular protein of the rat, the mouse and the human testis accumulating asymmetrically in the cytoplasm of round and elongating spermatids with its perinuclear location coinciding with the position of the developing acrosome-acroplaxome and the manchette. Profilin IV thus may regulate testicular actin cytoskeleton dynamics and play a role in acrosome generation and spermatid nuclear shaping.

Acrosome↗
PubMed2006

Puberty stage and spontaneous descent of acquired undescended testis: implications for therapy?

We assessed spontaneous descent of acquired undescended testis (UDT) at puberty. 299 Boys (aged 1.2-16.5 years, mean 9.4) with 350 acquired-UDT were examined annually during a 12.6-year period (mean 3.1). An acquired-UDT was defined as a previously intrascrotal testis which can no longer be manipulated into a stable scrotal position. Each year, position of the testis and pubertal development according to Tanner's stages were assessed. Early puberty was defined as puberty stage G2 (testicular volume 4-9 mL), mid-puberty as puberty stages G3 (testicular volume 10 mL) and G4 (testicular volume 11-15 mL), and late puberty as puberty stage G5 (testicular volume >15 mL). Follow-up was completed if spontaneous descent had occurred, if mid-pubertal orchidopexy (ORP) had to be performed, if the boy was lost for follow-up, or if pre-pubertal ORP was performed in another hospital. In 139 boys with 164 acquired-UDT follow-up was meanwhile completed. Twelve boys with 14 UDT were lost for follow-up. In an additional 16 boys with 21 UDT, ORP was performed in another hospital. In 98 of the remaining 129 (76.0%) acquired-UDT spontaneous descent at puberty occurred. Mean follow-up was 2.5 years (range 0.2-8.5). In 70 of 98 testes (71.4%) descent occurred in early puberty, in 26 of 98 testes (26.5%) in mid-puberty, and in two testes in late puberty. In 31 of 129 testes (24.0%) ORP had to be performed at mid (30 cases) or late (one case) puberty. In this series, 98 of 129 acquired-UDT (76.0%) descended spontaneously at puberty, whereas in 31 of 129 (24.0%) pubertal ORP was performed. If ORP is postponed until puberty stage G3 (testicular volume of 10 mL) three of four acquired-UDT will descend spontaneously.

Adolescent↗
PubMed1989

Male-enhanced antigen gene is phylogenetically conserved and expressed at late stages of spermatogenesis.

The male-enhanced antigen gene (Mea) was previously isolated from a mouse testicular cDNA library by using a pool of specific antisera against the serological H-Y antigen. The present studies characterize the human and mouse cDNAs and indicate that the MEA gene is conserved at both nucleic acid and protein levels. The corresponding mRNA encodes proteins of 18-20 kDa. The phylogenetic conservation could be extended to other mammalian species by Southern blot analysis. Although the Mea gene was transcribed as a 1-kilobase mRNA in most tissues, it was expressed at the highest level in adult testis. The testis-enhanced expression of the Mea gene was associated with germ cell development at late stages of spermatogenesis. Chromosome walking experiments identified two linked genes, A and B, located within 38 kilobases of human genomic sequence. Like the MEA gene, genes A and B were coordinately transcribed in the testis, which suggests that MEA and genes A and B are members of a gene family. In situ hybridization studies localized the MEA gene to the short arm of human chromosome 6 at band p21.1-21.3, close to the major histocompatibility complex locus. The genetic conservation and testis-specific expression of the MEA gene support the hypothesis that it plays an important role in mammalian spermatogenesis and/or testis development.

Amino Acid Sequence↗
PubMed2001

Substrate specificity plays an important role in uncoupling the catalytic and scaffolding activities of rat testis DNA topoisomerase IIalpha.

Topoisomerase II (topo II) is a dyadic enzyme found in all eukaryotic cells. Topo II is involved in a number of cellular processes related to DNA metabolism, including DNA replication, recombination and the maintenance of genomic stability. We discovered a correlation between the development of postnatal testis and increased binding of topo IIalpha to the chromatin fraction. We used this observation to characterize DNA-binding specificity and catalytic properties of purified testis topo IIalpha. The results indicate that topo IIalpha binds a substrate containing the preferred site with greater affinity and, consequently, catalyzes the conversion of form I to form IV DNA more efficiently in contrast to substrates lacking such a site. Interestingly, topo IIalpha displayed high-affinity and cooperativity in binding to the scaffold associated region. In contrast to the preferred site, however, high-affinity binding of topo IIalpha to the scaffold-associated region failed to result in enhanced catalytic activity. Intriguingly, competition assays involving scaffold-associated region revealed an additional DNA-binding site within the dyadic topo IIalpha. These results implicate a dual role for topo IIalpha in vivo consistent with the notion that its sequestration to the chromatin might play a role in chromosome condensation and decondensation during spermatogenesis.

Animals↗
PubMed2000

A new highly specific monoclonal antibody against placental alkaline phosphatase: a potential marker for the early detection of testis tumour.

OBJECTIVE: To develop specific monoclonal antibodies (mAbs) against human germ cell tumours. MATERIALS AND METHODS: A single-cell suspension obtained from tumour tissue fragments (consisting of both tumour and normal compartments) from a patient with seminoma was used as an immunogen. Spleen cells from immunized mice were used to develop mAbs. Tissue specificity, biochemical characteristics and competitive studies were analysed using immunocytochemical staining, dot blots and a Western blot analysis, to identify target antigen(s). RESULTS: The immunization protocol led to the development of 107 hybridomas, 90 of which were negative against the original tissue biopsies. The remaining 17 showed positivity against various tissue compartments. One selected mAb (ATC2) showed specific staining on germ cell tumours but not on normal tissues, and positive staining with some human tumour cell lines. The target antigen for ATC2 was confirmed to be placental alkaline phosphatase (PLAP) based on: Western blot analysis compared with commercially available PLAP; comparison of the data with another well-known anti-PLAP mAb (H17E2, although the two mAbs recognized different antigenic epitopes); heat resistance characteristics; high-performance liquid chromatography of the ATC2 target antigen and purified PLAP. CONCLUSION: The selected mAb ATC2 has high specificity for human germ cell tumours, the target antigen for ATC2 being PLAP, although the antigenic epitope(s) differ from those recognized by H17E2. Thus ATC2 may be useful for monitoring serum levels of PLAP in patients with testis cancer and may be relevant for detecting cancer cells in the semen of individuals with suspected testis cancer, particularly in those with equivocal findings on ultrasonography.

Alkaline Phosphatase↗
PubMed1978

A simple and rapid technique to isolate enriched populations of spermatocytes and spermatids from the immature rat testis.

A technique was developed to obtain enriched populations of large numbers of primary spermatacytes (70--81%) and of spermatids (75%) from immature rat testes (21--23 and 38 days old respectively) in a simple and rapid fashion. The cells were nearly all viable and membrane preservation was good. The testicular cells were dispersed by a mild mechanical treatment combined with an incubation with purified collagenase, and the cell populations were separated by centrifugation in a discontinuous dextran gradient in a cell culture medium.

Animals↗
PubMed2004

A variant of porcine thyroxine-binding globulin has reduced affinity for thyroxine and is associated with testis size.

The field of genomics applies the dissection of genetic differences toward an understanding of the biology of complex traits. Quantitative trait loci (QTL) for testis size, plasma FSH in boars, and body composition (backfat) have been identified near the centromere on the X chromosome in a Meishan-White Composite resource population. Since thyroid function affects Sertoli cell development and adult testis size in rodents, and thyroxine-binding globulin (TBG) maps to this region on the porcine X chromosome, TBG was a positional candidate gene for testis size. We discovered a polymorphism in exon 2 of the porcine TBG gene that results in an amino acid change of the consensus histidine to an asparagine. This single nucleotide polymorphism (SNP) resides in the ligand-binding domain of the mature polypeptide, and the Meishan allele is the conserved allele found in human, bovine, sheep, and rodent TBG. Binding studies indicate altered binding characteristics of the allelic variants of TBG with the asparagine (White Composite) isoform having significantly greater affinity for thyroxine than the histidine (Meishan) isoform. Alternate alleles in boars from the resource population are also significantly associated with testis weight. Therefore, this polymorphism in TBG is a candidate for the causative variation affecting testis size in boars.

Amino Acid Sequence↗
PubMed2005

Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate.

Normal spermatogenesis is essential for reproduction and depends on proper spermatogonial stem cell (SSC) function. Genes and signaling pathways that regulate SSC function have not been well defined. We report that glial cell-line-derived neurotrophic factor (GDNF) signaling through the RET tyrosine kinase/GFRA1 receptor complex is required for spermatogonial self-renewal in mice. GFRA1 and RET expression was identified in a subset of gonocytes at birth, was restricted to SSCs during normal spermatogenesis, and RET expressing cells were abundant in a cryptorchid model of SSC self-renewal. We used the whole-testis transplantation technique to overcome the limitation of neonatal lethality of Gdnf-, Gfra1-, and Ret-deficient mice and found that each of these genes is required for postnatal spermatogenesis and not for embryological testes development. Each mutant testis shows severe SSC depletion by Postnatal Day 7 during the first wave of spermatogenesis. These defects were due to lack of SSC proliferation and an inability of SSCs to maintain an undifferentiated state. Our results demonstrate that GDNF-mediated RET signaling is critical for the fate of undifferentiated spermatogonia and that abnormalities in this pathway may contribute to male infertility and testicular germ cell tumors.

Animals↗
PubMed1993

Proliferative activity of the developing seminiferous epithelium during prespermatogenesis in the golden hamster testis measured by bromodeoxyuridine labeling.

Bromodeoxyuridine (BrdU)-labeling was used to study the cell kinetics of the developing seminiferous epithelium in the testes of golden hamsters aged 10.5 to 27.5 days post conception (dpc), i.e., during a period beginning one developmental day before testicular differentiation (11.5 dpc) and extending to the appearance of the first "mature" spermatogonia. Supporting (Sertoli) cells continuously proliferate throughout the period studied. Labeling indices amount to about 30% between the 10.5th and 16.5th dpc, and subsequently decrease to levels below 10% on the 26.5th and 27.5th dpc. Germ cells (prespermatogonia) proliferate between the 10.5th and 15.5th dpc and again, after a period of mitotic quiescence, from the 24.5th dpc onwards. This pattern of prespermatogonial proliferation substantiates and further specifies the successive appearance of M-prespermatogonia (10.5th to 15.5th dpc: proliferating), T1-prespermatogonia (16.5th to 23.5th dpc: quiescent), and T2-prespermatogonia (24.5th to 27.5th dpc: proliferating). Thus, the M-prespermatogonial phase of germ cell proliferation is shown to commence at least 24 h before testicular differentiation. Transitions from M- to T1-phase and from T1- to T2-phase are rather abrupt. Both the latter observation and the comparison with oogonial development in the female at the corresponding time (onset of meiosis) indicate the presence of an underlying control mechanism operative during prespermatogenic development. Due to different nuclear staining patterns, the BrdU-labeling method allows temporal subdivision of the S-phase, thus opening up prospects of more detailed cell-kinetic analyses of the seminiferous epithelium.

Animals↗
PubMed2001

Glial cell line-derived neurotrophic factor (GDNF) and its receptors GFRalpha-1 and GFRalpha-2 in the human testis.

Glial cell line-derived neurotrophic factor (GDNF) and its receptors GFRalpha-1 and GFRalpha-2 were found in the human testis during fetal development (15-34 weeks of gestation) and in adult men (51-86 years of age) by means of RT-PCR, immunohistochemistry and Western blot techniques. Gene expression of GDNF could be established in the human testis and immunoreactivity (IR) for GDNF was detectable in Leydig cells, Sertoli cells, some spermatocytes and round spermatids as well as in smooth muscle cells of the wall of arterioles and small arteries. In the adult human testis, Sertoli and Leydig cells showed GFRalpha-1-IR, whereas GFRalpha-2-IR was located exclusively in Leydig cells. Different to man, in the rat GDNF-IR in Sertoli cells was detectable only until postnatal day10, providing evidence for species related variability in the expression of GDNF. These findings suggest a critical role for GDNF during the differentiation of testicular structures and provide evidence for an additional important function in the adult human and rodent testis.

Aged↗
PubMed2004

Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development?

The seminiferous tubule of the mammalian testis is largely composed of Sertoli and germ cells, which coordinate with Leydig cells in the interstitium and perform two major physiological functions, namely spermatogenesis and steroidogenesis respectively. Each tubule is morphologically divided into (i) the seminiferous epithelium composing Sertoli and germ cells, and (ii) the basement membrane (a modified form of extracellular matrix); underneath this lies the collagen fibril network, the myoid cell layer, and the lymphatic vessel, which collectively constitute the tunica propia. In the seminiferous epithelium, of rodent testes each type A1 spermatogonium (diploid, 2n) differentiates into 256 elongated spermatids (haploid, 1n) during spermatogenesis. Additionally, developing germ cells must migrate progressively from the basal to the luminal edge of the adluminal compartment so that fully developed spermatids can be released into the lumen at spermiation. Without this timely event of cell movement, spermatogenesis cannot reach completion and infertility will result. Yet developing round elongating/elongated spermatids must remain attached to the epithelium via a specialized Sertoli-germ cell actin-based adherens junction (AJ) type known as ectoplasmic specialization (ES), which is crucial not only for cell attachment but also for spermatid movement and orientation in the epithelium. However, the biochemical composition and molecular architecture of the protein complexes that constitute the ES have only recently been studied. Furthermore, the signalling pathways that regulate ES dynamics are virtually unknown. This review highlights recent advances in these two areas of research. It is expected that, if adequately expanded, these studies should yield new insights into the development of novel contraceptives targeted to perturb ES function in the testis. The potential to specifically target the ES may also mean that contraceptive action could be achieved without perturbing the hypothalamic-pituitary-testicular axis.

Actins↗