scholarly journals Epididymal cysteine-rich secretory proteins are required for epididymal sperm maturation and optimal sperm function

2018 ◽  
Vol 24 (3) ◽  
pp. 111-122 ◽  
Author(s):  
Jinghua Hu ◽  
D Jo Merriner ◽  
Anne E O’Connor ◽  
Brendan J Houston ◽  
Luc Furic ◽  
...  
2020 ◽  
Author(s):  
Simon Schneider ◽  
Farhad Shakeri ◽  
Christian Trötschel ◽  
Lena Arévalo ◽  
Alexander Kruse ◽  
...  

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.


2021 ◽  
Vol 548 ◽  
pp. 7-13
Author(s):  
Zongzhuang Wen ◽  
Dongyue Liu ◽  
Haixia Zhu ◽  
Xiaoyang Sun ◽  
Yu Xiao ◽  
...  

2015 ◽  
Vol 113 ◽  
pp. 226-243 ◽  
Author(s):  
Valérie Labas ◽  
Lucie Spina ◽  
Clémence Belleannee ◽  
Ana-Paula Teixeira-Gomes ◽  
Audrey Gargaros ◽  
...  

1994 ◽  
Vol 17 (5) ◽  
pp. 256-261 ◽  
Author(s):  
R. WEISSENBERG ◽  
S. YOSSEFI ◽  
Y. OSCHRY ◽  
I. MADGAR ◽  
L. M. LEWIN

2015 ◽  
Vol 35 (1) ◽  
pp. 374-385 ◽  
Author(s):  
Tao Luo ◽  
Qian-xing Zou ◽  
Yuan-qiao He ◽  
Hua-feng Wang ◽  
Na Li ◽  
...  

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.


Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 379-389 ◽  
Author(s):  
P Sipilä ◽  
J Jalkanen ◽  
I T Huhtaniemi ◽  
M Poutanen

Apart from condoms and vasectomy, modern contraceptive methods for men are still not available. Besides hormonal approaches to stop testicular sperm production, the post-meiotic blockage of epididymal sperm maturation carries lots of promise. Microarray and proteomics techniques and libraries of expressed sequence tags, in combination with digital differential display tools and publicly available gene expression databases, are being currently used to identify and characterize novel epididymal proteins as putative targets for male contraception. The data reported indicate that these technologies provide complementary information for the identification of novel highly expressed genes in the epididymis. Deleting the gene of interest by targeted ablation technology in mice or using immunization against the cognate protein are the two preferred methods to functionally validate the function of novel genesin vivo. In this review, we summarize the current knowledge of several epididymal proteins shown eitherin vivoorin vitroto be involved in the epididymal sperm maturation. These proteins include CRISP1, SPAG11e, DEFB126, carbonyl reductase P34H, CD52, and GPR64. In addition, we introduce novel proteinases and protease inhibitor gene families with potentially important roles in regulating the sperm maturation process. Furthermore, potential contraceptive strategies as well as delivery methods will be discussed. Despite the progress made in recent years, further studies are needed to reveal further details in the epididymal sperm maturation process and the factors involved, in order to facilitate the development of new epididymal contraceptives.


2010 ◽  
Vol 340 (3) ◽  
pp. 569-581 ◽  
Author(s):  
Kelly Moore ◽  
Kyle Lovercamp ◽  
Dongyan Feng ◽  
Jennifer Antelman ◽  
Miriam Sutovsky ◽  
...  

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