Effects of Products of Activated Immune Cells and Recombinant Cytokines on Spontaneous and Ionophore‐Induced Acrosome Reaction

Dimitrov, Dimitar G.; Petrovská, Marianna

doi:10.1111/j.1600-0897.1996.tb00156.x

Cited by 13 publications

(11 citation statements)

References 24 publications

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“…, 2007). The TNF‐α results are in agreement with the findings of Dimitrov & Petrovská (1996) and Bian et al. (2007) where TNF‐α was reported to decrease both spontaneous and ionophore‐induced AR.…”

Section: Discussionsupporting

confidence: 91%

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Effects of tumour necrosis factor alpha and interleukin‐6 on progesterone and calcium ionophore‐induced acrosome reaction

Lampiao

Plessis

2009

Int J of Andrology

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For human spermatozoa to successfully fertilize the oocyte, they need to undergo a timely acrosome reaction (AR). Factors which disturb the AR may lead to fertilization failure. The objective of this study was to investigate the effects of two cytokines namely tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) on the spontaneous, calcium ionophore-induced and progesterone-induced human sperm AR. Twenty-two normal semen samples were treated with increasing concentrations of TNF-alpha and IL-6 after spermatozoa were isolated by a double wash swim-up method. The AR was induced by calcium ionophore A23187 and progesterone. The AR was determined by using fluorescein isothiacyanate Pisum sativum agglutinin and observed under fluorescence microscope. Both TNF-alpha and IL-6 could decrease the spontaneous, ionophore and progesterone-induced AR (p < 0.05) in a dose-dependent manner. TNF-alpha showed a more potent inhibiting effect than IL-6 by inhibiting the AR at lower concentrations. This study has demonstrated that TNF-alpha and IL-6 play a role in inhibiting both the non-physiological as well as physiologically elicited AR by calcium ionophore and progesterone respectively.

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Section: Discussionsupporting

confidence: 91%

“…(1997) used concentrations ranging from 5 to 160 pg/mL sperm. TNF‐α has been reported to have an inhibitory effect on the AR (Dimitrov & Petrovská, 1996; Bian et al. , 2007).…”

Section: Introductionmentioning

confidence: 99%

Effects of tumour necrosis factor alpha and interleukin‐6 on progesterone and calcium ionophore‐induced acrosome reaction

Lampiao

Plessis

2009

Int J of Andrology

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“…In humans, although the level of IgA antibodies does not appear as critical as IgG antibodies for fertilization suppression, a combination of IgA on sperm and high serum anti-sperm antibody levels reduces the probability of fertilization [25,27,28]. In addition, immunologic cytokines released by activated lymphocytes, macrophages, and other white blood cell products might also be involved in fertility inhibition, since evidence to date indicates that these soluble factors can adversely affect several aspects of sperm function (i.e., motility, AR, fusion ability) [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Potential Contraceptive Use of Epididymal Proteins: Immunization of Male Rats with Epididymal Protein DE Inhibits Sperm Fusion Ability1

Ellerman

Brantúa

Martı́nez

et al. 1998

Biology of Reproduction

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Rat epididymal protein DE associates with the sperm surface during maturation and participates in sperm-egg fusion. Immunization of male rats with DE raised specific antibodies and produced a significant reduction in the animals' fertility. The present study focused on determining the in vivo mechanism involved in fertility inhibition. Wistar males were injected with DE, and antibody levels and animal fertility were evaluated. Results revealed an association between the two parameters, since animals with absorbance values lower than 0.5 in ELISA presented high fertility rates (66%, 100%) while those with absorbance values higher than 0.5 exhibited the lowest fertility rates (0%, 33%). Histological studies showed no evidence of orchitis, epididymitis, or vasitis in DE-immunized animals. ELISA results revealed the presence of anti-DE antibodies in epididymal and vas deferential fluids. Indirect immunofluorescence and ELISA experiments indicated that these antibodies would not interfere with the synthesis or secretion of DE or with its association with the sperm surface. Finally, while epididymal sperm recovered from DE-immunized animals presented no changes in motility, viability, or ability to undergo capacitation and acrosome reaction, they exhibited a significant decrease in their ability to fuse with zona-free eggs, with no effect on their ability to bind to the oolemma. Together these results indicate that immunization of male rats with epididymal protein DE specifically interferes with the sperm fertilizing ability, supporting the use of epididymal proteins for contraceptive vaccine development.

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“…IL-6 has been shown to affect the fertilization capacity of human sperm as it induces acrosomal exocytosis, and at higher levels it reduces sperm viability and motility (32,47). IL-6, TNF-␣, and IFN-␥ were shown to induce capacitation and AR of human sperm, but IL-1 could not induce these processes (31). Another study showed that TNF-␣, IFN-␥, and IL-8 did not affect AR (48).…”

Section: Discussionmentioning

confidence: 95%

“…In vitro studies have shown that the AR can be initiated in preincubated spermatozoa either spontaneously or by various physiological inducers, such as zona pellucida glycoproteins and follicular fluid, and nonphysiological inducers such as calcium ionophore, A23184 (30). Spontaneous and ionophore-induced ARs were significantly increased by interferon (IFN)-␥, TNF-␣, and IL-6, but not by IL-1␤ (31,32).…”

mentioning

confidence: 98%

Effect of Interleukin-1 Receptor Antagonist Gene Deletion on Male Mouse Fertility

et al. 2008

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Members of the IL-1 family are pleiotropic cytokines that are involved in inflammation, immunoregulation, and other homeostatic functions in the body. IL-1alpha, IL-1beta, and the IL-1 antagonistic molecule [IL-1 receptor antagonist (IL-1 Ra)] are present in the testis under normal homeostasis, and they further increase upon infection/inflammation. In the present study, we examined the effect of IL-1 Ra gene deletion on male mouse fertility. Male mice [wild type (WT) and IL-1 Ra knockout (KO)] were mated with WT females, and the birth and number of offspring were recorded 21-45 d after mating. Furthermore, the concentration, motility, and morphology of sperm isolated from the cauda of the epididymis were evaluated. The ability of the calcium ionophore (A23187) to induce acrosome reaction (AR) in the sperm of WT and IL-1 Ra KO mice was compared with their ability to fertilize in vitro oocytes from WT females. The direct effect of IL-1alpha and IL-1beta on AR and abnormal morphology in sperm from WT were evaluated. The levels of IL-1alpha and IL-1beta in the testes of WT and IL-1 Ra KO mice were examined by specific ELISA and real-time PCR. Our results show a significant reduction in the capacity of IL-1 Ra KO male mice to fertilize WT females (P < 0.05). Furthermore, the number of offspring in mice fertilized with IL-1 Ra KO male mice was significantly lower than with WT males (P < 0.05). Sperm concentration and the percentage of motile sperm from IL-1 Ra KO and WT were similar; however, the percentage of sperm with abnormal morphology (mainly in the head) and acrosome-reacted sperm cells were significantly higher in the IL-1 Ra KO, compared with that of WT males (P < 0.05). In vitro, the ability of sperm from IL-1 Ra KO male mice to fertilize oocytes from WT females was significantly lower than sperm from WT mice (P < 0.05). In addition, the percentage of reacted sperm from IL-1 Ra KO, spontaneously without ionophore induction, was significantly higher than from WT (P < 0.05). Sperm from WT underwent induction of AR only by ionophore; however, sperm from IL-1 Ra KO were unable to undergo the AR by ionophore, indicating that they are induced and, thus, are inactive in fertilization. Testicular IL-1alpha and IL-1beta levels were significantly higher in IL-1 Ra KO, compared with WT male mice (P < 0.05). The addition of recombinant IL-1alpha or IL-1beta to sperm from a WT mouse induced their AR, and significantly increased abnormal sperm morphology, as compared with controls (P < 0.05). This effect was neutralized by the addition of IL-1 Ra. Our results indicate the involvement of IL-1 in sperm physiology, affecting its morphology and fertilization ability. Higher than homeostatic levels of IL-1 in the testis, as observed in IL-1 Ra KO mice, impaired the ability of sperm to fertilize oocytes. Together, these results may explain some of the male infertility cases with an infection/inflammation background and may hint at the ability to use IL-1 Ra in future therapeutic strategies in these cases.

show abstract

Effects of Products of Activated Immune Cells and Recombinant Cytokines on Spontaneous and Ionophore‐Induced Acrosome Reaction

Abstract: Some cases of infertility may result from a defective acrosome reaction (premature acrosome loss or insufficient acrosome response to the stimulants) caused by products of activated lymphocytes and macrophages that are released into the male and female reproductive tracts.

Cited by 13 publications

References 24 publications

Effects of tumour necrosis factor alpha and interleukin‐6 on progesterone and calcium ionophore‐induced acrosome reaction

Effects of tumour necrosis factor alpha and interleukin‐6 on progesterone and calcium ionophore‐induced acrosome reaction

Potential Contraceptive Use of Epididymal Proteins: Immunization of Male Rats with Epididymal Protein DE Inhibits Sperm Fusion Ability1

Effect of Interleukin-1 Receptor Antagonist Gene Deletion on Male Mouse Fertility

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