The effect of ornidazole on fertility and epididymal sperm function in rats

Background: Matrine is a bioactive alkaloid that has a variety of pharmacological effects and is widely used in Chinese medicine. However, its effects on male reproduction are not well known. In this study, we aimed to investigate the in vitro toxicity of matrine on mature mouse sperm. Methods: Mouse cauda epididymal sperm were exposed to matrine (10-200 µM) in vitro. The viability, motility, capacitation, acrosome reaction and fertilization ability of the mouse sperm were examined. Furthermore, the intracellular calcium concentration ([Ca2+]i), calcium (Catsper) and potassium (Ksper) currents, and phosphorylation of extracellular signal regulated kinases 1/2 (p-ERK1/2) of the sperm were analyzed. Results: After exposure to 100 µM or more of matrine, mouse cauda epididymal sperm exhibited a significant reduction in total motility, progressive motility, linear velocity and acrosome reaction rate induced by Ca2+ ionophore A23187. As a result, the fertilization ability of mouse sperm was remarkably decreased by matrine. Our data further demonstrated that matrine significantly reduced sperm [Ca2+]i and [Ca2+]i-related p-ERK1/2; however, both the CatSper and KSper currents, which are thought to interactively regulate Ca2+ influx in sperm, were not affected by matrine. Conclusion: Our findings indicate that matrine inhibits mouse sperm function by reducing sperm [Ca2+]i and suppressing the phosphorylation of ERK1/2.

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Prm2 deficiency triggers a Reactive Oxygen Species (ROS)-mediated destruction cascade during epididymal sperm maturation in mice

10.1101/2020.05.05.075929 ◽

2020 ◽

Author(s):

Simon Schneider ◽

Farhad Shakeri ◽

Christian Trötschel ◽

Lena Arévalo ◽

Alexander Kruse ◽

...

Keyword(s):

Oxidative Stress ◽

Male Infertility ◽

Molecular Mechanisms ◽

Sperm Maturation ◽

Preimplantation Embryos ◽

Sperm Function ◽

Epididymal Sperm ◽

Small Proteins ◽

Infertile Men ◽

New Treatment

AbstractProtamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Prm2-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like SOD1 and PRDX5, ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.Significance statementSexual reproduction requires the successful fertilization of female eggs by male sperm. The generation of functional sperm is a complex, multi-step differentiation process known as spermatogenesis that takes places in the male testis. One important step for physiological sperm function is the incorporation of small proteins, known as protamines into the DNA. Defects within this process are common causes of male infertility. However, the underlying molecular mechanisms still remain largely unknown, thus preventing targeted therapies. Here, we identify the molecular cascade being initiated in protamine-deficient murine sperm that ultimately impedes fertilization. Our findings have broad implications for the development of new treatment options for infertile men with faulty protamination that seek medical advice.

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Effect of Fertility Blend® Administration on the Epididymal Sperm Function Parameters of Vasectomized Mice: Physiological and Genetical Study as Model for Obstructive Azoospermic Men

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2018.12.1.558 ◽

2018 ◽

Vol 12 (1) ◽

pp. 132-136

Author(s):

Saad S. Al-Dujaily ◽

Hazim I. Al-Ahmed ◽

Jasim Al-Ethawi ◽

Haidar A. Al-Ebrahimi

Keyword(s):

Male Fertility ◽

Treated Group ◽

Sperm Function ◽

Obstructive Azoospermia ◽

Epididymal Sperm ◽

Nutrient Supplements ◽

Sperm Characters ◽

Different Sources

Male Fertility Blend® is a new nutrient supplements containing many constituents especially a plant called Dong quai(Angelia Sinensis). The plant extract has been used to facilitate the sperm function parameters. However, the studies concern on its effects on epididymal sperms of vasectomized males and obstructive azoospermia are very rare. Thus, this investigation was designed to elucidate the role of Male Fertility Blend® (MFB) formula on the in vivo epididymal sperm characters and DNA fragmentations of vasectomized male mice as a model for man. In this study, the orally administration of 3.4 µg/ml MFB was used for vasectomized and non-vasectomized mice along 35 days. The results revealed a significant (p≤0.05) increment in certain sperm function parameters of vasectomized mice by using fertility Blend® than that of not treated by this supplement. The percentage of progressive and unprogressive active sperm motility using MFB was significantly (P≤0.05) increased compared with non-treated group. It was concluded that the MFB formula containing different sources of energy and variety of factors that sustain the epididymal sperm of healthy and vasectomized mice. Therefore this supplement can be utilized for males complaining from obstructive azoospermia and other factors of infertility.

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