Biomedical subjects

Mamiko Maekawa

Publications and source records attributed to Mamiko Maekawa.

At least 19 recordsLinked to original sources

PubMed2006

Azoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) gene.

Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) is a member of the Aatyk family of kinases that comprises Aatyk1, Brek/Lmtk2/Aatyk2, and Aatyk3. Although several potential roles have been proposed for Brek and other Aatyk family members, the physiological functions of these kinases remain unclear. Here, we report that Brek(-/-) male mice are infertile, with azoospermia. Detailed histological analysis revealed that Brek(-/-) germ cells differentiated normally until the round-spermatid stage, but failed to undergo the normal change in morphology to become elongated spermatids. Testicular somatic cells appeared normal in these mice. Expression of Brek in testis was restricted to the germ cells, suggesting that the maturations of germ cells in Brek(-/-) mice are affected in a cell-autonomous manner. On the basis of these findings, we concluded that Brek is essential for a late stage of spermatogenesis. Further clarification of the mechanism by which Brek regulates spermatogenesis may help identify new targets for reproductive contraceptives and treatments against infertility.

Animals↗

PubMed2006

Anti-estrogen ICI 182.780 and anti-androgen flutamide induce tyrosine phosphorylation of cortactin in the ectoplasmic specialization between the Sertoli cell and spermatids in the mouse testis.

Our previous study revealed that the ectoplasmic specialization (ES) was deleted by the treatment of anti-estrogen, ICI 182.780 (ICI), and anti-androgen, flutamide (FLUT) in mouse testis. Also, expression of cortactin, an F-actin-binding protein, was decreased by the treatment of FLUT in mouse testis. Cortactin has been suggested to promote actin polymerizer at the ES in the testis, and also actin depolymerization is induced by tyrosine phosphorylation of cortactin. The present study revealed that exogenous treatment of ICI and FLUT caused the deletion of the cortactin in the apical ES and the increase of tyrosine phosphorylated cortactin in mouse testis. These results suggest that the sex hormone antagonists', ICI and FLUT, induced actin depolymerization and tyrosine phosphorylation of cortactin in the mouse testis. Also, the present study may be a key to elucidate the adverse affect exogenous compounds that affect spermiation.

Androgen Antagonists↗

PubMed2006

Flutamide depresses expression of cortactin in the ectoplasmic specialization between the Sertoli cells and spermatids in the mouse testis.

Flutamide (FLUT) has potent anti-androgenic activity and is used in the medical field and in a screening test to detect endocrinologically active compounds. Our previous study demonstrated that FLUT induced histological deformation of spermatids and ultrastructural defects of the apical ectoplasmic specialization (ES) in the mouse testis. The apical ES is an actin-based junctional structure between the Sertoli cells and germ cells. Cortactin, an actin-binding protein, is found in the actin layer of ES. The protein level of cortactin was decreased in FLUT-treated testes as shown by Western blot analysis. The detailed analysis indicated that the protein level was drastically decreased in FLUT-treated seminiferous tubules of stages from VI to IX. Immunohistochemistry and immunoelectron microscopy showed that FLUT depressed cortactin expression in the apical ES. In addition, the effect of FLUT on cortactin localization appeared between 12 h and 8 days (about 180 h) after a one-day treatment. These results suggest that FLUT depressed the expression of cortactin in the apical ES with stage specificity. Therefore, the initial target of FLUT may be the cell-cell interactions between the Sertoli and germ cells. To our knowledge, this study is the first to document the decrease of cortactin expression in the abnormal apical ES following treatment with FLUT.

Androgen Antagonists↗

PubMed2006

Fyn is required for haloperidol-induced catalepsy in mice.

Fyn-mediated tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunits has been implicated in various brain functions, including ethanol tolerance, learning, and seizure susceptibility. In this study, we explored the role of Fyn in haloperidol-induced catalepsy, an animal model of the extrapyramidal side effects of antipsychotics. Haloperidol induced catalepsy and muscle rigidity in the control mice, but these responses were significantly reduced in Fyn-deficient mice. Expression of the striatal dopamine D(2) receptor, the main site of haloperidol action, did not differ between the two genotypes. Fyn activation and enhanced tyrosine phosphorylation of the NMDA receptor NR2B subunit, as measured by Western blotting, were induced after haloperidol injection of the control mice, but both responses were significantly reduced in Fyn-deficient mice. Dopamine D(2) receptor blockade was shown to increase both NR2B phosphorylation and the NMDA-induced calcium responses in control cultured striatal neurons but not in Fyn-deficient neurons. Based on these findings, we proposed a new molecular mechanism underlying haloperidol-induced catalepsy, in which the dopamine D(2) receptor antagonist induces striatal Fyn activation and the subsequent tyrosine phosphorylation of NR2B alters striatal neuronal activity, thereby inducing the behavioral changes that are manifested as a cataleptic response.

Animals↗

PubMed2006

Formaldehyde exposure in a gross anatomy laboratory--personal exposure level is higher than indoor concentration.

GOAL, SCOPE AND BACKGROUND: Cadavers for gross anatomy laboratories are usually prepared by using embalming fluid which contains formaldehyde (FA) as a principal component. During the process of dissection, FA vapors are emitted from the cadavers, resulting in the exposure of medical students and their instructors to elevated levels of FA in the laboratory. The American Conference of Governmental Industrial Hygienists (ACGIH) has set a ceiling limit for FA at 0.3 ppm. In Japan, the Ministry of Health, Labour and Welfare has set an air quality guideline defining two limit values for environmental exposure to FA: 0.08 ppm as an average for general workplaces and 0.25 ppm for specific workplaces such as an FA factory. Although there are many reports on indoor FA concentrations in gross anatomy laboratories, only a few reports have described personal FA exposure levels. The purpose of the present study was to clarify personal exposure levels as well as indoor FA concentrations in our laboratory in order to investigate the relationship between them. METHODS: The gross anatomy laboratory was evaluated in the 4th, 10th and 18th sessions of 20 laboratory sessions in total over a period of 10 weeks. Air samples were collected using a diffusive sampling device for organic carbonyl compounds. Area samples were taken in the center and four corners of the laboratory during the entire time of each session (4-6 hours). Personal samples were collected from instructors and students using a sampling device pinned on each person's lapel, and they were 1.1 to 6 hours in duration. Analysis was carried out using high performance liquid chromatography. RESULTS AND DISCUSSION: Room averages of FA concentrations were 0.45, 0.38 and 0.68 ppm for the 4th, 10th and 18th sessions, respectively, ranging from 0.23 to 1.03 ppm. These levels were comparable to or relatively lower than the levels reported previously, but were still higher than the guideline limit for specific workplaces in Japan and the ACGIH ceiling limit. The indoor FA concentrations varied depending on the contents of laboratory sessions and seemed to increase when body cavity or deep structures were being dissected. In all sessions but the 4th, FA levels at the center of the room were higher than those in the corners. This might be related to the arrangement of air supply diffusers and return grills. However, it cannot be ruled out that FA levels in the corners were lowered by leakage of FA through the doors and windows. Average personal exposure levels were 0.80, 0.45 and 0.51 ppm for instructors and 1.02, 1.08 and 0.89 ppm for students for the 4th, 10th and 18th session, respectively. The exposure levels of students were significantly higher than the mean indoor FA concentrations in the 4th and 10th sessions, and the same tendency was also observed in the 18th session. The personal exposure level of instructors was also significantly higher than the indoor FA level in the 4th session, while they were almost the same in the 10th and 18th sessions. Differences in behavior during the sessions might reflect the differential personal exposure levels between students and instructors. CONCLUSION: The present study revealed that, if a person is close to the cadavers during the gross anatomy laboratory, his/her personal exposure level is possibly 2 to 3-fold higher than the mean indoor FA concentration. This should be considered in the risk assessment of FA in gross anatomy laboratories. RECOMMENDATION AND OUTLOOK: If the risk of FA in gross anatomy laboratories is assessed based on the indoor FA levels, the possibility that personal exposure levels are 2 to 3-fold higher than the mean indoor FA level should be taken into account. Otherwise, the risk should be assessed based on the personal exposure levels. However, it is hard to measure everyone's exposure level. Therefore, further studies are necessary to develop a method of personal exposure assessment from the indoor FA concentration.

Air Pollution, Indoor↗

PubMed2006

Oligo-astheno-teratozoospermia in mice lacking RA175/TSLC1/SynCAM/IGSF4A, a cell adhesion molecule in the immunoglobulin superfamily.

RA175/TSLC1/SynCAM/IGSF4A (RA175), a member of the immunoglobulin superfamily with Ca2+-independent homophilic trans-cell adhesion activity, participates in synaptic and epithelial cell junctions. To clarify the biological function of RA175, we disrupted the mouse Igsf4a (Ra175/Tslc1/SynCam/Igsf4a Ra175) gene. Male mice lacking both alleles of Ra175 (Ra175-/-) were infertile and showed oligo-astheno-teratozoospermia; almost no mature motile spermatozoa were found in the epididymis. Heterozygous males and females and homozygous null females were fertile and had no overt developmental defects. RA175 was mainly expressed on the cell junction of spermatocytes, elongating and elongated spermatids (steps 9 to 15) in wild-type testes; the RA175 expression was restricted to the distal site (tail side) but not to the proximal site (head side) in elongated spermatids. In Ra175-/- testes, elongated and mature spermatids (steps 13 to 16) were almost undetectable; round spermatids were morphologically normal, but elongating spermatids (steps 9 to 12) failed to mature further and to translocate to the adluminal surface. The remaining elongating spermatids at improper positions were finally phagocytosed by Sertoli cells. Furthermore, undifferentiated and abnormal spermatids exfoliated into the tubular lumen from adluminal surfaces. Thus, RA175-based cell junction is necessary for retaining elongating spermatids in the invagination of Sertoli cells for their maturation and translocation to the adluminal surface for timely release.

Animals↗

PubMed2006

Estrogen agonists, 17beta-estradiol, bisphenol A, and diethylstilbestrol, decrease cortactin expression in the mouse testis.

Previous reports have revealed that estrogen agonists or anti-androgenic chemicals induce abnormal spermiogenesis in rodents. In the seminiferous epithelium, the apical ectoplasmic specialization (ES) is an actin-based (cell-cell) junctional structure developing between the Sertoli cells and spermatids as is the basal ES also--although it is located between adjoining Sertoli cells. In the apical and basal ES are several adhesion complex proteins that control the spermatid developing process. Cortactin, an actin-binding protein, is one of the ES adhesion proteins, combining with several cell-cell adhesions associating proteins. In the present study, 17beta-estradiol (E2, 1.2 microg/kg), bisphenol A (BPA, 2.4 microg/kg), and diethylstilbestrol (DES, 2.5 microg/kg) were subcutaneously injected in ICR 12-week-old male mice. Mice testes were observed for the expression of cortactin protein after E2, BPA, and DES treatments by Western blot analysis, immunohistochemical analysis, and immunoelectron microscopic analysis. Observations showed that the immunoreactivity of the treated testes was significantly decreased. The immunohistochemical reactivity of cortactin in the apical ES was decreased in the treated testis. In immunoelectron microscopic observations, ultrastructural immunolocalizations of cortactin protein in the apical ES by both E2 and BPA were decreased, and the immuno-gold particles of apical and basal ES by DES were much less than the control. In the toxicological field, cortactin may be considered to be one of the indicator proteins of abnormal spermiogenesis which is affected by exogenous chemicals, such as endocrine disrupting chemicals. In summary, this study helps toward understanding the cortactin protein expression underlying the histological abnormalities of spermatogenesis induced by exogenous hormonal chemical treatment.

Animals↗

PubMed2005

Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression.

Mice with disrupted mammalian PcG (Polycomb group) genes commonly show skeletal transformation of anterior-posterior identities. Disruption of the murine M33 gene, a PcG member, displayed posterior transformation of the vertebral columns and sternal ribs. In addition, failure of T-cell expansion and hypoplasia and sex-reversal of the gonads, have been observed. In the present study, we identified defects in the splenic and adrenal formation of M33-knock-out (KO) mice on a C57BL/6 genetic background. The spleen in these animals was smaller than in the wild-type mice and was spotted red because of nonuniform distribution of blood cells. Histologic examination revealed disorganization of the vascular endothelium and its surrounding structures, and immunohistochemistry demonstrated disturbances in vascular formation and colonization of immature hematopoietic cells. These splenic phenotypes observed in the M33-KO mice were quite similar to those seen in Ad4BP/SF1 (Nr5a1) knock-outs. Moreover, the adrenal glands of M33-KO and Ad4BP/SF1 heterozygous KO mice were smaller than those of the wild-type mice. Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of the M33 knock-outs all indicated significantly low expression of adrenal 4 binding protein/steroidogenic factor-1 (Ad4BP/SF-1), indicating that M33 is an essential upstream regulator of Ad4BP/SF1. In agreement with these observations, chromatin immunoprecipitation assays with adrenocortical Y-1 cells revealed direct binding of the M33-containing PcG to the Ad4BP/SF1 gene locus.

Adrenal Glands↗

PubMed2005

HANP1/H1T2, a novel histone H1-like protein involved in nuclear formation and sperm fertility.

We cloned a testis-specific cDNA from mice that encodes a histone H1-like, haploid germ cell-specific nuclear protein designated HANP1/H1T2. The HANP1/H1T2 protein was specifically localized to the nuclei of murine spermatids during differentiation steps 5 to 13 but not to the nuclei of mature sperm. HANP1/H1T2 contains an arginine-serine-rich domain and an ATP/GTP binding site, and it binds to DNA, ATP, and protamine. To investigate the physiological role of HANP1/H1T2, we generated Hanp1/H1T2-disrupted mutant mice. Homozygous Hanp1/H1T2 mutant males were infertile, but females were fertile. Although a substantial number of sperm were recovered from the epididymides, their shape and function were abnormal. During sperm morphogenesis, the formation of nuclei was disturbed and protamine-1 and -2 were only weakly detectable in the nuclei. The chromatin packaging was aberrant, as demonstrated by electron microscopy and biochemical analysis. The mutant sperm exhibited deficient motility and were not competent to fertilize eggs under in vitro fertilization conditions; however, they were capable of fertilizing eggs via intracytoplasmic sperm injection that resulted in the birth of healthy progeny. Thus, we found that HANP1/H1T2 is essential for nuclear formation in functional spermatozoa and is specifically involved in the replacement of histones with protamines during spermiogenesis. At the time of submission of the manuscript, we found an independent publication by Martianov et al. (I. Martianov, S. Brancorsini, R. Catena, A. Gansmuller, N. Kotaja, M. Parvinen, P. Sassone-Corsi, and I. Davidson, Proc. Natl. Acad. Sci. USA 102:2808-2813, 2005) that reported similar results.

Adenosine Triphosphate↗

PubMed2004

Rosbin: a novel homeobox-like protein gene expressed exclusively in round spermatids.

Mammalian spermiogenesis is a complex process occurring in a highly coordinated fashion within the seminiferous tubules. To elucidate the molecular mechanisms controlling haploid germ cell differentiation, we have isolated haploid germ cell- specific cDNA clones from a subtracted cDNA library of mouse testis. One of these cDNAs, Rosbin, is 3.2 kilobases (kb) long and has an open reading frame of 2385 nucleotides encoding a putative protein of 795 amino acid residues. A computer-mediated homology search revealed that it contained a domain similar to that of homeobox genes. Northern blot analysis revealed a 3.2-kb mRNA expressed exclusively in male germ cells. Transcription of the Rosbin gene was not observed in prepubertal testis but became detectable after Day 23. By Western blot analysis the protein encoded by this gene had a molecular mass of 89 kDa, expressing specifically in the testis and localized to the nucleus of stages IV-VIII haploid round spermatids, predominantly at stages VII-VIII of spermatogenesis. ROSBIN is associated with and is most likely phosphorylated by protein kinase A. We suggest that it plays an important role in transcriptional regulation in haploid germ cells.

Amino Acid Sequence↗

PubMed2004

Impairment of spermatogenesis leading to infertility.

Highly differentiated spermatozoa are generated through multiple cellular and molecular processes maintained by Sertoli cells. The cellular events associated with germ cells include proliferation, protein folding and transportation, as well as sequential changes in chromatin and cell organelles. These processes are strictly controlled by the expression of specific genes, including transcription and DNA replication/repair. This complex spermatogenesis is impaired by a mutation such as gene knockout, which leads to a variety of morphological and functional abnormalities found in mature spermatozoa. An overview of spermatogenesis impairment induced by gene knockout is provided in the present review.

Animals↗

PubMed2004

Mice deficient in the axonemal protein Tektin-t exhibit male infertility and immotile-cilium syndrome due to impaired inner arm dynein function.

The haploid germ cell-specific Tektin-t protein is a member of the Tektin family of proteins that form filaments in flagellar, ciliary, and axonemal microtubules. To investigate the physiological role of Tektin-t, we generated mice with a mutation in the tektin-t gene. The homozygous mutant males were infertile, while the females were fully fertile. Sperm morphology and function were abnormal, with frequent bending of the sperm flagella and marked defects in motility. In vitro fertilization assays showed that the defective spermatozoa were able to fertilize eggs. Electron microscopic examination showed that the dynein inner arm structure was disrupted in the sperm flagella of tektin-t-deficient mice. Furthermore, homozygous mutant mice had functionally defective tracheal cilia, as evidenced by altered dynein arm morphology. These results indicate that Tektin-t participates in dynein inner arm formation or attachment and that the loss of Tektin-t results in impaired motility of both flagella and cilia. Therefore, the tektin-t gene is one of the causal genes for immotile-cilium syndrome/primary ciliary dyskinesia.

Animals↗

PubMed2004

Activation of the Smad pathway in glomeruli from a spontaneously diabetic rat model, OLETF rats.

BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) mediates the excess accumulation of extracellular matrix in the diabetic kidney. Smad family proteins have been identified as signal transducers for the TGF-beta superfamily. We sought to characterize the role of Smad proteins in mediating TGF-beta responses in the development of diabetic nephropathy. METHODS: We evaluated the time course of TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli from spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using immunohistochemistry and Western blot analysis. RESULTS: The glomeruli of diabetic OLETF rats showed not only accelerated activation of Smad3, but also enhanced protein expression of Smad2 and Smad3, which occurred in parallel to the increased expression of TGF-beta and fibronectin compared with glomeruli of control, Long-Evans Tokushima Otsuka (LETO) rats at 30 weeks of age. No differences were found in TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli between the two strains at 12 weeks of age when OLETF rats were not diabetic. CONCLUSIONS: The enhancement of Smad protein expression and activation may be involved in the TGF-beta signaling cascade that plays an important role in the development of diabetic nephropathy through progressive expansion of the mesangial matrix.

Animals↗

PubMed2004

Stage-specific expression of mouse germ cell-less-1 (mGCL-1), and multiple deformations during mgcl-1 deficient spermatogenesis leading to reduced fertility.

A mouse homologue of Drosophila germ cell-less, mouse germ cell-less-1 (mgcl-1), is highly expressed in the testis. Previous report revealed that the fertility of the mgcl-1(-/-) male mice is reduced significantly as a result of various morphological abnormalities in the sperm (Kimura et al., 2003). To elucidate the function of mgcl-1 in spermatogenesis, the expression of mGCL-1 in the wild-type testis was examined. Immunohistochemical studies demonstrated that mGCL-1 first appeared in the nuclei of the pachytene spermatocytes at stage VI of the seminiferous epithelium, and existed in those of spermatids until step 8 during spermatogenesis. mGCL-1 was not detectable after step 9 spermatids. The testicular cells and epididymal sperm were further analyzed morphologically using mgcl-1(-/-) mice. In the testis, deformed nuclei first occurred in the pachytene spermatocytes at stage VI, which is consistent with the time of the first appearance of the mGCL-1 protein in the wild-type testis. Abnormal nuclei and acrosomes were found in spermatids after step 5, and nuclei of the spermatids and epididymal sperm were frequently invaginated. In addition, variously deformed sperm such as bent-neck, multi-headed or multi-nucleated sperm were observed in the mgcl-1(-/-) cauda epididymidis. However, several key structures such as the acroplaxome marginal ring (Kierszenbaum et al., 2003), postacrosomal sheath, and posterior ring apparently formed. In addition, MN7 and MN13, essential substances for fertilization that are located in sperm heads, were detectable in the mgcl-1 null sperm. These observations provide important insights into the mechanisms regulating the nuclear architecture and causes of human infertility.

Animals↗

PubMed2004

Failure to assemble the peri-nuclear structures in GOPC deficient spermatids as found in round-headed spermatozoa.

Deletion of the GOPC gene encoding mouse GOPC (Golgi-associated PDZ- and coiled-coil motif-containing protein) causes infertile round-headed spermatozoa, which have acrosome-less round heads and deformed tails (Yao et al, 2002). This study investigated how GOPC deficient spermatids fail to assemble the peri-nuclear structures in round-headed spermatozoa during spermiogenesis in GOPC knockout mouse testes. In step 1-8 spermatids, Golgi-derived proacrosomal vesicles that are transported to the perinuclear region formed acrosome-like vesicles of various sizes, called pseudoacrosomes. The marginal ring of the acroplaxome, which is generally formed between the descending edge of a developing acrosome and nuclear envelope in a wild spermatid, was poorly formed between the pseudoacrosome and nuclear envelope. In step 9-11 elongating spermatids, a majority of pseudoacrosomes were detached from the nucleus and disappeared from the perinuclear region by spermiation. Concomitantly, several failures occurred on the nucleus, manchette, postacrosomal sheath (perinuclear theca), and posterior ring. Ectoplasmic specializations were poorly formed, and did not always associate with developing spermatids. Consequently, spermatid nuclear elongation to form round-headed spermatozoa developed was impaired. In addition to these sequential failures, the posterior ring deficiency was attributed to the tail deformation destined to occur during epididymal maturation as reported in an accompanying paper (Suzuki-Toyota et al, 2004 in this issue), its eventual phenotype being reminiscent of the round-headed spermatozoa of human infertile globozoospermia.

Adaptor Proteins, Signal Transducing↗

PubMed2004

The coiled tail of the round-headed spermatozoa appears during epididymal passage in GOPC-deficient mice.

Male mice deleting the gene encoding GOPC (Golgi-associated PDZ- and coiled-coil motif-containing protein) are infertile, showing globozoospermia with a coiled tail (Yao et al., 2002). We confirmed how and where tail anomalies were produced in spermatids and epididymal spermatozoa by light and electron microscopy. During spermiogenesis, tail formation occurred normally, but a defect was found at the posterior ring. Thereafter, remarkable sperm tail deformations were induced during epididymal passage. In the proximal caput epidiymidis, the tails remained normal and straight, but most of them coiled around the nucleus in the cauda epididymidis. Coiling is presumed to occur with the migration of the cytoplasmic droplet by the absence of the posterior ring. The connecting piece of the coiled tail was often dislocated or separated from the implantation fossa. Many mitochondria were separated from the outer dense fibers (ODFs) and formed a stratified mitochondrial sheath. Due to this, the distal part of the midpiece became bared of the mitochondrial sheath. The bared ODFs were often bent and disorganized. Tail deformities are attributed to weak or incomplete adhesion between the following structures: 1) plasma membrane and nuclear envelope at the posterior ring, 2) connecting piece and implantation fossa, and 3) mitochondria and ODFs. These defects result in a coiled tail, tail dislocation from the implantation fossa, and the stratified mitochondrial sheath accompanying bared ODFs in the midpiece, respectively. Thus the posterior ring is significant in preventing coiled tail formation. The GOPC-deficient spermatozoa provide a valuable model not only for head but also for tail anomalies.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Adverse effects of bisphenol A to spermiogenesis in mice and rats.

Either a 20 or 200 microg/kg body weight/injection of bisphenol A (BPA) was subcutaneously administered to adult mice and rats for 6 days, and the effects on the testes were investigated by electron and light microscopy. Abnormalities were observed in the spermatids: acrosomal vesicles, acrosomal caps, acrosomes and nuclei of the spermatids were severely deformed. The ectoplasmic specialization between the Sertoli cell and spermatids were also affected: incomplete specialization, redundant ectopic specialization and aplasia were observed. Rats and mice responded similarly to BPA. There were no dose dependencies between the 20- and 200 microg/kg body weight/injection groups. The ectoplasmic specialization between adjoining Sertoli cells, or blood-testis barrier, was not affected. Since similar adverse effects were observed when adult mice were treated with beta-estradiol 3-benzoate, the effects of BPA reported here seem to reflect the estrogenic effects on the testes. Animals kept for an additional two months after cessation of the administration were shown to be fertile and the testes showed normal histology, indicating that the adverse effects were transitory.

Acrosome↗

PubMed2003

Ectoplasmic specializations in the Sertoli cell: new vistas based on genetic defects and testicular toxicology.

Abstract The ectoplasmic specialization is a unique junctional complex formed in two cortical areas of the Sertoli cell in the mammalian testis: one near the base of the seminiferous epithelium forming the blood-testis barrier, and the other near the lumen of the seminiferous tubule embracing the acrosome region of the developing spermatids. The specialization consists of the Sertoli cell plasma membrane, a subsurface cistern of the endoplasmic reticulum and a layer of closely packed actin filaments that is sandwiched between the plasma membrane and the subsurface cistern. No functions of the specializations other than the blood-testis barrier have been established. However, over the past decade, knowledge about the ectoplasmic specialization has been steadily accumulating and, in particular, there has been a tremendous increase in knowledge based on molecular biological approaches to specialization-associated proteins, including tight junction-associated proteins, based on phenotype analyses of gene-knockout mice and mutant animals, and based on analyses of the effects of exogenous estrogens, so-called endocrine disruptors. Progress in studies on the ectoplasmic specialization will facilitate the elucidation of numerous important questions regarding spermatogenesis, including the pathogenesis of azoospermia and the mechanisms of action of endocrine disruptors.

Animals↗