scholarly journals Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice

2019 ◽  
Vol 116 (37) ◽  
pp. 18498-18506 ◽  
Author(s):  
Yoshitaka Fujihara ◽  
Taichi Noda ◽  
Kiyonori Kobayashi ◽  
Asami Oji ◽  
Sumire Kobayashi ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Gene Families ◽  
Gene Clusters ◽  
Mutant Mice ◽  
Male Reproductive Tract ◽  
Sperm Migration ◽  
Specific Proteins ◽  
Multiple Male

CRISPR/Cas9-mediated genome editing technology enables researchers to efficiently generate and analyze genetically modified animals. We have taken advantage of this game-changing technology to uncover essential factors for fertility. In this study, we generated knockouts (KOs) of multiple male reproductive organ-specific genes and performed phenotypic screening of these null mutant mice to attempt to identify proteins essential for male fertility. We focused on making large deletions (dels) within 2 gene clusters encoding cystatin (CST) and prostate and testis expressed (PATE) proteins and individual gene mutations in 2 other gene families encoding glycerophosphodiester phosphodiesterase domain (GDPD) containing and lymphocyte antigen 6 (Ly6)/Plaur domain (LYPD) containing proteins. These gene families were chosen because many of the genes demonstrate male reproductive tract-specific expression. AlthoughGdpd1andGdpd4mutant mice were fertile, disruptions ofCstandPategene clusters andLypd4resulted in male sterility or severe fertility defects secondary to impaired sperm migration through the oviduct. While absence of the epididymal protein families CST and PATE affect the localization of the sperm membrane protein A disintegrin and metallopeptidase domain 3 (ADAM3), the sperm acrosomal membrane protein LYPD4 regulates sperm fertilizing ability via an ADAM3-independent pathway. Thus, use of CRISPR/Cas9 technologies has allowed us to quickly rule in and rule out proteins required for male fertility and expand our list of male-specific proteins that function in sperm migration through the oviduct.

scholarly journals Male Infertility, Oxidative Stress and Antioxidants

2021 ◽  
Author(s):  
Vegim Zhaku ◽  
Ashok Agarwal ◽  
Sheqibe Beadini ◽  
Ralf Henkel ◽  
Renata Finelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Healthy Lifestyle ◽  
Free Radical Scavengers ◽  
Semen Parameters ◽  
Ros Production ◽  
Modus Operandi ◽  
Male Reproductive Tract

Within the male reproductive system, oxidative stress (OS) has been identified as prevailing etiology of male infertility. The effects of reactive oxygen species (ROS) on male fertility depend on the dimensions, “modus operandi” of the ROS and the oxido-reduction potential (ORP) of the male reproductive tract. Hereupon, for an adequate response to OS, the cells of our body are endowed with a well-sophisticated system of defense in order to be protected. Various antioxidant enzymes and small molecular free radical scavengers, maintain the delicate balance between oxidants and reductants (antioxidants), crucial to cellular function and fertility. Therapeutic use of antioxidants is an optimal and coherent option in terms of mitigating OS and improving semen parameters. Therefore, recognizing and managing OS through either decreasing ROS levels or by increasing antioxidant force, appear to be a requesting approach in the management of male infertility. However, a clear defined attitude of the experts about the clinical efficacy of antioxidant therapy is still deprived. Prominently, antioxidant such as coenzyme Q10, vitamin C and E, lycopene, carnitine, zinc and selenium have been found useful in controlling the balance between ROS production and scavenging activities. In spite of that, healthy lifestyle, without smoke and alcohol, everyday exercise, reduction of psychological stress and quality well-designed meals, are habits that can overturn male infertility.

scholarly journals Expression of the rhesus glycoproteins, ammonia transporter family members, RHCG and RHBG in male reproductive organs

Reproduction ◽  
2013 ◽  
Vol 146 (3) ◽  
pp. 283-296 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Jill W Verlander ◽  
Mary E Handlogten ◽  
Ki-Hwan Han ◽  
Paul S Cooke ◽  
...  
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Immunoblot Analysis ◽  
Reproductive Organs ◽  
Normal Male ◽  
Male Reproductive Tract ◽  
Clear Cells ◽  
Principal Cells ◽  
Cellular Expression ◽  
Transporter Family

The rhesus glycoproteins, Rh B glycoprotein (RHBG) and Rh C glycoprotein (RHCG), are recently identified ammonia transporters. Rhcg expression is necessary for normal male fertility, but its specific cellular expression is unknown, and Rhbg has not been reported to be expressed in the male reproductive tract. This study sought to determine the specific cellular expression of Rhcg, to determine whether Rhbg is expressed in the male reproductive tract, and, if so, to determine which cells express Rhbg using real-time RT-PCR, immunoblot analysis, and immunohistochemistry. Both Rhbg and Rhcg were expressed throughout the male reproductive tract. In the testis, high levels of Rhbg were expressed in Leydig cells, and Rhcg was expressed in spermatids during the later stages of their maturation (steps 13–16) in stages I–VIII of the seminiferous epithelium cycle. In the epididymis, basolateral Rhbg was present in narrow cells in the initial segment, in principal cells in the upper corpus, and in clear cells throughout the epididymis. Apical Rhcg immunolabel was present in principal cells in the caput and upper corpus epididymidis and in clear cells in the middle and lower corpus and cauda epididymidis. In the vas deferens, apical Rhcg immunolabel and basolateral Rhbg immunolabel were present in some principal cells and colocalized with H+-ATPase immunolabel. We conclude that both Rhbg and Rhcg are highly expressed in specific cells in the male reproductive tract where they can contribute to multiple components of male fertility.

Cross-species analysis of the mammalian β-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract

2005 ◽  
Vol 23 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Amar A. Patil ◽  
Yibin Cai ◽  
Yongming Sang ◽  
Frank Blecha ◽  
Guolong Zhang
Keyword(s):  
Host Defense ◽  
Reproductive Tract ◽  
Evolutionary Relationship ◽  
Gene Clusters ◽  
Last Common Ancestor ◽  
Host Defense Peptides ◽  
Male Reproductive Tract ◽  
Preferential Expression ◽  
Syntenic Gene ◽  
Carboxy Terminal

Mammalian β-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the β-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most β-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several β-defensins. Furthermore, all β-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of β-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some β-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat β-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human β-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most β-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of β-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.

scholarly journals LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility†

2020 ◽  
Vol 102 (5) ◽  
pp. 1033-1044
Author(s):  
Dan Wang ◽  
Liping Cheng ◽  
Wenjuan Xia ◽  
Xiaofei Liu ◽  
Yueshuai Guo ◽  
...  
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Mass Spectrometry Analysis ◽  
Small Subset ◽  
Vitro Fertilization ◽  
Spectrometry Analysis ◽  
Human Fertilization ◽  
Sperm Migration

Abstract Fertilization is one of the fundamental biological processes, but so far, we still do not have a full understanding of the underlying molecular mechanism. We have identified a human acrosome protein, LY6/PLAUR domain containing 4 (LYPD4), expressed specifically in human testes and sperm, and conserved within mammals. Mouse Lypd4, also specific to the testis and sperm, is essential for male fertility. LYPD4 protein first appeared in round spermatids during acrosome biogenesis and became part of acrosomes during spermatogenesis and in mature sperm. Lypd4 knockout mice are infertile with normal sperm number and motility. Mutant sperm, however, failed to reach oviduct during sperm migration inside the female reproductive tract, leading to fertilization failure and infertility. In addition, Lypd4 mutant sperms were unable to fertilize denuded egg via IVF (in vitro fertilization) but could fertilize eggs within intact Cumulus-Oocyte Complex, supporting an additional role in sperm-zona interaction. Out of more than five thousand spermatozoa proteins identified by mass spectrometry analysis, only a small subset of proteins (26 proteins) was changed in the absence of LYPD4, revealing a whole proteome picture of mutant sperm defective in sperm migration and sperm-zona binding. ADAM3, a key component of fertilization complex, as well as other sperm ADAM proteins are significantly reduced. We hence propose that LYPD4 plays an essential role in mammalian fertilization, and further investigation of its function and its interaction with other sperm membrane complexes may yield insights into human fertilization and novel strategy to improve IVF success.

scholarly journals Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 98
Author(s):  
Yoo-Jin Park ◽  
Myung-Geol Pang
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Ros Generation ◽  
Male Reproductive Tract ◽  
Proteomic Data ◽  
Epididymal Maturation ◽  
Sperm Dna

Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm–egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also established the new signaling pathway using previous proteomic data associated with male fertility, to understand the overall role of mitochondria in male fertility. The pathway revealed that male infertility is associated with a loss of mitochondrial proteins in spermatozoa, which induces low sperm motility, reduces OXPHOS activity, and results in male infertility.

pH and male fertility: making sense on pH homeodynamics throughout the male reproductive tract

2019 ◽  
Vol 76 (19) ◽  
pp. 3783-3800 ◽  
Author(s):  
Raquel L. Bernardino ◽  
David F. Carrageta ◽  
Mário Sousa ◽  
Marco G. Alves ◽  
Pedro F. Oliveira
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Male Reproductive Tract ◽  
Making Sense

scholarly journals Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2898-2905 ◽  
Author(s):  
Kerstin W. Sinkevicius ◽  
Muriel Laine ◽  
Tamara L. Lotan ◽  
Karolina Woloszyn ◽  
John H. Richburg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Cell Function ◽  
Critical Role ◽  
Estrogen Receptor Α ◽  
Male Reproductive Tract ◽  
Efferent Ductule

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.

Role of Acid/Base Transporters in the Male Reproductive Tract and Potential Consequences of Their Malfunction

Physiology ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 417-428 ◽  
Author(s):  
Nuria Pastor-Soler ◽  
Christine Piétrement ◽  
Sylvie Breton
Keyword(s):  
Environmental Factors ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Sperm Maturation ◽  
Genetic Mutations ◽  
Acid Base ◽  
Male Reproductive Tract ◽  
Acidification Capacity ◽  
And Storage

Acid/base transporters play a key role in establishing an acidic luminal environment for sperm maturation and storage in the male reproductive tract. Impairment of the acidification capacity of the epididymis, via either genetic mutations or exposure to environmental factors, may have profound consequences on male fertility.

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