Sperm antibodies in rat models of male hormonal contraception and vasectomy

1999 ◽  
Vol 11 (1) ◽  
pp. 49 ◽  
Author(s):  
Esko Veräjänkorva ◽  
Mika Martikainen ◽  
Antti Saraste ◽  
Jari Sundström ◽  
Pasi Pöllänen
Keyword(s):  
Reproductive Tract ◽  
Pathological Condition ◽  
Hormonal Contraception ◽  
Seminiferous Tubules ◽  
Cell Nuclei ◽  
Molecular Ratio ◽  
Apoptotic Morphology ◽  
Post Operation ◽  
Sperm Antibodies ◽  
Intact Rats

The presence of sperm antibodies correlates with nearly every pathological condition of the male reproductive tract. In the seasonal breeder, mink, a decrease in gonadotrophin secretion and testicular regression also induces sperm antibodies. Because the Sertoli cells and the principal cells of the epididymis (i.e. the cells mainly responsible for protection of germ cells from autoimmune destruction) are dependent on androgens, and because the androgen concentration decreases in both the testis and epididymis during male hormonal contraception, the presence of IgG class sperm antibodies in serum was studied in rats during the suppression and recovery phases of testosterone contraception and after vasectomy. Five-centimetre long testosterone implants were placed under the dorsal skin of rats under pentobarbitone anaesthesia. The control rats received empty implants. All implants were left in the rats for 27 or 53 days. The total number of testicular antigens detected by sera from the vasectomized rats increased significantly until 66 days post-operation, and then decreased to the levels of intact rats. The number of testicular antigens detected by sera from rats receiving contraceptive doses of testosterone did not increase before the testosterone capsules were removed, but at 40 days post removal of the silastic capsules, the number of antigens detected by the sera was significantly higher than in intact rats and at 77 days post removal of the silastic capsules, the number of antigens detected by the sera was significantly higher than at 27 days after starting testosterone administration. No significant changes in the number of antigens detected by the sera could be observed after the implanting of empty capsules or after their removal. Vasectomy mostly induced antibodies against testicular antigens in the molecular ratio ranges of 70–82, 25–33 and 21–24.5 kD. Antibodies against antigens in these molecular ratio ranges were not significantly induced during or after treatment with contraceptive doses of testosterone. Cell nuclei with apoptotic morphology could be observed in the seminiferous tubules of the vasectomized rats, but DNA in situ 3′-end labelling of testes could not confirm any differences between the testes of vasectomized and sham-operated rats or between testosterone-treated and empty implant-treated rats. CD3 + T cells could not be observed in the testes of any of the treatment groups. These results suggest that the immunological conditions remain stable in the testes after vasectomy and during testosterone treatment, but that the animals are more prone to develop autoantibodies after vasectomy and during recovery from treatment with exogenous testosterone.

Prospects for hormonal contraception in the male

2000 ◽  
Vol 8 (2) ◽  
pp. 127-142
Author(s):  
RA Anderson
Keyword(s):  
Reproductive Tract ◽  
Hormonal Contraception ◽  
Seminiferous Tubules ◽  
Male Reproductive Tract ◽  
Scientific Advance ◽  
Testicular Spermatozoa ◽  
Stage Of Development ◽  
The Subject ◽  
Potential Methods ◽  
Developed World

Female-dependent methods of contraception have been the subject of considerable scientific advance since the introduction of the combined contraceptive pill, offering effective and male-independent contraception, but there is an emerging emphasis that men should be more involved in family planning. The supremacy of modern, female methods in the developed world obscures the fact that one-third of all couples worldwide rely on a male-dependent method of contraception, mostly the condom or withdrawal, methods that have been used since antiquity. Potential methods of male contraception include withdrawal of the gonadotrophic support to the testis, interference with spermatogenesis within the seminiferous tubules, or with post-testicular functions. Effects on maturation within the epididymis can be induced by chloro-6-deoxy sugars or plant-derived glycosides. Although advances in assisted conception, particularly associated with intracytoplasmic sperm injection (ICSI), have demonstrated the functional competence of the nucleus and centriole of testicular spermatozoa and other less mature forms, it has been suggested that normal passage through the male reproductive tract is necessary for conventional conception. Advances in both testicular and post-testicular methods of contraception have been hampered by toxicity and remain in preclinical testing, reflecting the limited extent of (and thus the need for) scientific knowledge in this area. While progress in these areas is fully acknowledged, the pretesticular hormonal approach is currently at a considerably more advanced stage of development with prospects for a real product becoming increasingly likely on a realistic time-scale. This review will therefore confine itself to this, the hormonal approach.

scholarly journals Studies on the hypophysectomised ferret. II. - Spermatogenesis

1932 ◽  
Vol 112 (775) ◽  
pp. 146-152 ◽  
Keyword(s):  
Body Weight ◽  
Pituitary Gland ◽  
Reproductive Tract ◽  
Complete Loss ◽  
Male Rat ◽  
Seminiferous Tubules ◽  
Clear Cut ◽  
Resulting Condition ◽  
Made In ◽  
Male Genital

Smith (1930) has shown that all parts of the reproductive tract of the male rat show pronounced atrophy after hypophysectomy. The testes are much reduced in size and are flabby. The seminiferous tubules show a corresponding diminution in size and all indications of spermatogenesis are absent. A more immediate effect of ablation of the pituitary gland is a complete loss of interest in the female. Richter and Wislocki (1930) also noted atrophy of the male genital organs of the rat after hypophysectomy, but in no great detail. Hypophysectomy has not yet been performed on a species in which the male shows a clear cut anœstrous period such as is found in the male ferret (Allanson, 1932). The present work was undertaken to find out if the testes of the ferret react to hypophysectomy in the same way as those of the rat, and to compare the resulting condition of the testes with that found during anœstrus. Further light on the activity of the pituitary body during anœstrus might thus be obtained. In addition, it was hoped to determine the rate of regression after hypophysectomy and to compare this with that found at the end of the breeding season. No attempt will be made in this or the following paper to deal with the general effects of hypophysectomy, but it may be mentioned that loss of body weight, if any, was slight during the time covered by these experiments.

scholarly journals Engineering Highly Homogenous Tetravalent IgGs with Enhanced Sperm Agglutination Potency

2020 ◽  
Author(s):  
Bhawana Shrestha ◽  
Alison Schaefer ◽  
Elizabeth C. Chavez ◽  
Alexander J. Kopp ◽  
Timothy M. Jacobs ◽  
...  
Keyword(s):  
Side Effects ◽  
Hormonal Contraception ◽  
Infertile Woman ◽  
Exogenous Hormones ◽  
Infertile Women ◽  
Unintended Pregnancies ◽  
Naturally Occurring ◽  
Promising Strategy ◽  
Sperm Antibodies

AbstractMillions of women avoid using available contraceptives and risk unintended pregnancies every year, due to perceived and/or real side-effects associated with the use of exogenous hormones. Naturally occurring anti-sperm antibodies can prevent fertilization in immune infertile women by limiting sperm permeation through mucus, particularly multivalent antibodies such as sIgA that offers robust agglutination potencies. Unfortunately, sIgA remains challenging to produce in large quantities and easily aggregates. Here, we designed two tetravalent anti-sperm IgGs with a Fab domain previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscore the multimerization of IgG as a promising strategy to improve existing mAb therapeutics.

THE INFLUENCE OF OVERCROWDING ON SPERMATOGENESIS, SIZE OF LEYDIG-CELL NUCLEI (HISTOMETRICAL INVESTIGATION), AND THE ADRENAL CORTICOSTERONE CONTENTS IN MICE

1973 ◽  
Vol 74 (4) ◽  
pp. 783-791 ◽  
Author(s):  
K. Gärtner ◽  
H. Reznik-Schüller ◽  
G. Reznik
Keyword(s):  
Population Size ◽  
Group Size ◽  
Adult Male ◽  
Leydig Cell ◽  
Relative Frequency ◽  
Seminiferous Tubules ◽  
Cell Nuclei ◽  
Nmri Mice ◽  
Testosterone Secretion ◽  
Adrenal Corticosterone

ABSTRACT Adult male NMRI-mice were kept alone or in groups of 5, 10, 20, 30, 40 and 60 animals for 28 days and were then sacrificed. The corticosterone levels of their adrenals were determined and their testes were examined histometrically. The corticosterone levels of the adrenals increased two-fold with increasing population size. Furthermore the increased population size caused a suppression of some testicular functions: the seminiferous tubules decreased up to 20 % and the relative frequency of the spermatids up to 10 % whereas the numbers of spermatocytes and spermatogonias increased correspondingly. A decrease of about 25 % of the testosterone dependent postmeiotic stages of spermatogenesis is assumed. Since the diameters of the Leydig-cell nuclei decreased about 20 %, a reduction of the testicular testosterone secretion can be projected. All measurements proved the group with 5 animals to be the most favourable group size.

scholarly journals Testosterone immunoreactivity in the seminiferous epithelium of rat testis: effect of treatment with ethane dimethanesulfonate.

1989 ◽  
Vol 37 (11) ◽  
pp. 1667-1673 ◽  
Author(s):  
R Schulz ◽  
F Paris ◽  
P Lembke ◽  
V Blüm
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Time Course ◽  
Seminiferous Epithelium ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Seminiferous Tubules ◽  
Treatment Level ◽  
Cell Nuclei ◽  
Testicular Weight

Androgens drive spermatogenesis by processes that are largely unknown. Direct effects on germ cells and indirect effects mediated via testicular somatic elements are currently under consideration, and specific localization of androgens in seminiferous tubules may provide information as regards this. Adult male rats were injected with ethane dimethanesulfonate (EDS; 75 mg/kg body weight) or vehicle. Testes were fixed and paraffin-embedded for localization of testosterone immunoreactivity 1 and 2 weeks after treatment, using the unlabeled antibody (PAP) technique. Plasma testosterone dropped from a pre-treatment level of 2.3 ng/ml to below 0.2 ng/ml 3 days after EDS injection and remained at low levels until the end of observation, accompanied by a progressive decrease in testicular weight. In the seminiferous tubules of vehicle-injected males, testosterone immunoreactivity was found in nuclei of spermatocytes and spermatids and in nuclei and the cytoplasm of Sertoli cells, and showed typical variations according to the stage of spermatogenesis. One week after EDS treatment, immunoreactivity had disappeared from the seminiferous epithelium. Two weeks after treatment, staining of germ cells was detected in two out of four males. The disappearance and reappearance of immunoreactivity coincided with the time course of EDS effects on rat Leydig cells, and we conclude that it corresponds to androgen specifically localized in fixed, paraffin-embedded tissue. Because staining of germ cell nuclei varied with the stage of spermatogenesis, the technique may detect a physiologically relevant androgen fraction; its location suggests that androgens may also directly affect certain germ cell stages.

scholarly journals Recombinant human granulocyte colony-stimulating factor alleviates liver fibrosis in bile duct-ligated mice

2019 ◽  
Vol 6 (6) ◽  
pp. 3222-3232
Author(s):  
Huy Quang Do ◽  
Trinh Van Le ◽  
Minh Thanh Dang ◽  
Tien-Trieu Pham-Le ◽  
Luan Van Tran ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Pathological Condition ◽  
Histological Grade ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Duct Ligation ◽  
Post Operation ◽  
Stimulating Factor

Introduction: Biliary atresia (BA) is the leading cause of liver fibrosis and failure in neonates with surgical jaundice, leading to poor outcome. Clinical and animal studies showing that granulocyte colony-stimulating factor (GCSF) treatment could improve liver fibrosis and cirrhosis suggest that GCSF may be offered as a low-cost intervention to improve the course of BA. This study aims to test the hypothesis that 10 µg/kg/day x 5 days of GCSF could improve liver function, reduce molecular pro-fibrotic markers and decrease liver fibrosis in a mouse model of bile duct ligation (BDL). Methods: Balb/c mice underwent Sham surgery, or BDL for seven days followed by subcutaneous GCSF administration at 10 µg/kg/day for five consecutive days. Twelve days post-operation, blood samples were taken from the facial vein for leukocyte/neutrophil count and for measurement of serum enzymatic activities. The median lobe of the liver was acquired for total RNA and protein extraction. Moreover, the median liver lobe was used for hematoxylin-eosin staining, sirius red staining, and for visualization by immunohistochemistry (IHC). Results: Twelve days post-operation, GCSF-treated bile duct-ligated (BDL) mice had a higher survival rate than that of placebo-treated mice (hazard ratio=1.88, p=0.084). The GCSF-treated mice had diminished liver serum transaminase activities (AST: 228.92 ± 222.67 vs. 313.46 ± 164.80 IU/L; ALP: 573.24 ± 177.89 IU/L vs. 471.75 ± 117.92 IU/L). GCSF treatment also reduced fibrosis with down-regulation of expression of pro-fibrotic markers including TGF-β1 (-2.61-fold mRNA), α-SMA (-2.46-fold mRNA; -1.88-fold protein, p<0.001) and collagen (-3.28-fold mRNA; -1.79-fold collagen deposit, p=0.0055). Moreover, GCSF treatment led to an improvement of histological grade and a reduction of extension of ductular structures caused by cholestasis (-1.77-fold CK7-positive bile ducts, p<0.0001; -2.33-fold CK7 positivity, p<0.0001). Conclusion: Administration of GCSF (10 μg/kg/day) for five consecutive days improved the pathological condition of BDL mice. In this study, the positive effect of GCSF could be eventually surpassed due to end-stage liver disease caused from BDL in the mouse model. Further experiments are required to elucidate the effects and mechanisms of GCSF on bile obstruction.  

scholarly journals The Transformative Impact of Extracellular Vesicles on Developing Sperm

2021 ◽  
Author(s):  
Michael P Rimmer ◽  
Christopher D Gregory ◽  
Rod T Mitchell
Keyword(s):  
Extracellular Vesicles ◽  
Acrosome Reaction ◽  
Reproductive Tract ◽  
Seminiferous Tubules ◽  
Parent Cell ◽  
Male Reproductive Tract ◽  
Future Fertility ◽  
Cell Niche ◽  
Transformative Impact

Objective To review the role of extracellular vesicles (EVs) released from the male reproductive tract and their impact on developing sperm. We discuss how sperm exiting the seminiferous tubules, although developmentally mature, require further modification. Acquisition of various functions including increased motility, transfer of cargoes and ability to undertake the acrosome reaction are mediated through the interaction between sperm and EVs. Methods A review of the literature identified that EVs are released from different portions of the male reproductive tract, notably the epididymis and prostate. These EVs interact with sperm as they pass from the seminiferous tubules to the epididymis and vas deferens prior to ejaculation. Results EVs are small lipid bound particles carrying bespoke RNA, protein and lipid cargoes. These cargoes are loaded based on the state of the parent cell and are used to communicate with recipient cells. In sperm, these cargoes are essential for post testicular modification. Sperm extracted from the proximal epididymis are poorly motile and unable to carry out the acrosome reaction. Conclusions Interaction between developing sperm and EVs is important for the subsequent function of sperm. Little is known however about EVs released from the seminiferous tubules to developing sperm or in the fetal and pre-pubertal testes. A greater understanding, especially in the formation and development of the spermatogonial stem cell niche may lead to new insights as to how damage to this niche may be prevented and preserve future fertility.

scholarly journals Testicular dysgenesis syndrome and phthalate exposure: A review of literature

2021 ◽  
Vol 71 (6) ◽  
pp. 508-543
Author(s):  
Pınar Erkekoglu ◽  
Aylin Özyurt ◽  
Anıl Yirün ◽  
Deniz Çakır
Keyword(s):  
Endocrine Disruptors ◽  
Semen Quality ◽  
Pathological Condition ◽  
Endocrine System ◽  
Seminiferous Tubules ◽  
Testicular Dysgenesis Syndrome ◽  
Testicular Cells ◽  
Phthalate Exposure ◽  
Food Packages ◽  
Testicular Dysgenesis

Endocrine disruptors are chemicals that interfere with the body's endocrine system and cause adverse effects in biological systems. Phthalates are a group of man-made chemicals which are mainly used as plasticizers and classified as endocrine disruptors. They are also used in cosmetic and personal care products as color or smell fixators. Moreover, phthalates are present in inks, adhesives, sealants, automobile parts, tools, toys, carpets, medical tubing and blood storage bags, and food packages. Pathological condition known as "testicular dysgenesis syndrome" (TDS) or "phthalate syndrome" is usually linked to phthalate exposure and is coined to describe the rise in alterations in reproductive health in men, such as reduced semen quality (decrease in sperm counts, sperm motility and increase in abnormal sperms), hypospadias, cryptorchidism, reduced anogenital distance and early-life testicular cancer. Phthalates are suggested to cause direct effect on gonadal and non-gonadal tissues, impair the differentiation and morphogenesis of seminiferous tubules and accessory sex organs and testicular cells (both Sertoli and Leydig cells), alter estradiol and/or testosterone levels, decrease insulin-like 3 (INSL3) peptide production, impair spermatogenesis and lead to epigenetic alterations, all of which may lead to TDS. This review will mainly focus on phthalates as causes of TDS and their mechanisms of action.

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