scholarly journals Adam21 is dispensable for reproductive processes in mice

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12210
Author(s):  
Yinghong Chen ◽  
Chao Liu ◽  
Yongliang Shang ◽  
Liying Wang ◽  
Wei Li ◽  
...  
Keyword(s):  
Male Fertility ◽  
Leydig Cells ◽  
Potential Role ◽  
Male Reproduction ◽  
Biological Processes ◽  
Intracellular Lipid ◽  
Knockout Mouse Model ◽  
Meiotic Progression ◽  
Reproductive Processes ◽  
Oil Red O

Background As a group of membrane-anchored proteins, the proteins containing a disintegrin and metalloprotease domain (ADAMs) control many biological processes, especially for male fertility. Mouse Adam21 was previously found to be specifically expressed in the somatic cells and germ cells of testes, but its functional role during spermatogenesis and male reproductive processes is still unknown. Methods Adam21-null mice were created using the CRISPR/Cas9 system. Quantitative real-time PCR was used for analyzing of gene expression. Histological, cytological and immunofluorescence staining were performed to analyze the phenotypes of mouse testis and epididymis. Intracellular lipid droplets (LDs) were detected by Oil red O (ORO) staining and BODIPY staining. Fertility and sperm characteristics were also detected. Results Here, we successfully generated an Adam21 conventional knockout mouse model via CRISPR/Cas9 technology so that we can explore its potential role in male reproduction. We found that male mice lacking Adam21 have normal fertility without any detectable defects in spermatogenesis or sperm motility. Histological analysis of the seminiferous epithelium showed no obvious spermatogenesis difference between Adam21-null and wild-type mice. Cytological analysis revealed no detectable defects in meiotic progression, neither Sertoli cells nor Leydig cells displayed any defect compared with that of the control mice. All these results suggest that Adam21 might not be essential for male fertility in mice, and its potential function still needs further investigation.

scholarly journals X-linked palindromic gene families 4930567H17Rik and Mageb5 are dispensable for male mouse fertility

2021 ◽  
Author(s):  
Evan R Stark-Dykema ◽  
Eden A. Dulka ◽  
Emma R Gerlinger ◽  
Jacob L Mueller
Keyword(s):  
Male Fertility ◽  
Potential Role ◽  
Gene Families ◽  
Male Reproduction ◽  
Sperm Function ◽  
Sequence Comparisons ◽  
Human Orthologs ◽  
Head Morphology ◽  
Palindromic Sequences ◽  
Predominant Expression

Mammalian sex chromosomes are enriched for large, nearly-identical, palindromic sequences harboring genes expressed predominately in testicular germ cells. Discerning if individual palindrome-associated gene families are essential for male reproduction is difficult due to challenges in disrupting all copies within a gene family. Here we generate precise, independent, deletions to assess the reproductive roles of two X-linked palindromic gene families with spermatid-predominant expression, 4930567H17Rik or Mageb5. Via sequence comparisons, we find mouse 4930567H17Rik and Mageb5 have human orthologs, 4930567H17Rik is rapidly diverging in rodents and primates, and 4930567H17Rik is harbored in a palindrome in humans and mice, while Mageb5 is not. Mice lacking either 4930567H17Rik or Mageb5 gene families do not have detectable defects in male fertility, fecundity, spermatogenesis, or in gene regulation, but do show differences in sperm head morphology, suggesting a potential role in sperm function. We conclude that while all palindrome-associated gene families are not essential for male fertility, large palindromes influence the evolution of their associated gene families.

scholarly journals The Impact of Bone on the Biology of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Gerard Karsenty
Keyword(s):  
Muscle Function ◽  
Male Fertility ◽  
Leydig Cells ◽  
Memory Loss ◽  
Age Related ◽  
Systematic Exploration ◽  
Biology Of Aging ◽  
The Impact ◽  
The Brain ◽  
Regulate Energy Metabolism

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

scholarly journals Kindlin-2 in Sertoli cells is essential for testis development and male fertility in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaochun Chi ◽  
Weiwei Luo ◽  
Jiagui Song ◽  
Bing Li ◽  
Tiantian Su ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Barrier Structure ◽  
Male Mice ◽  
Sperm Development

AbstractKindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.

scholarly journals RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

2021 ◽  
Vol 22 (19) ◽  
pp. 10285
Author(s):  
Pietro Laneve ◽  
Paolo Tollis ◽  
Elisa Caffarelli
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Potential Role ◽  
Noncoding Rnas ◽  
Rna Metabolism ◽  
Biological Processes ◽  
Diagnostic Biomarkers ◽  
Defective Rna ◽  
Almost All ◽  
Lateral Sclerosis

RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases. In recent decades, considerable efforts have been devoted to the characterization of noncoding RNAs (ncRNAs) and to the study of their role in the homeostasis of the nervous system (NS), where they are highly enriched. Acting as major regulators of gene expression, ncRNAs orchestrate all the steps of the differentiation programs, participate in the mechanisms underlying neural functions, and are crucially implicated in the development of neuronal pathologies, among which are neurodegenerative diseases. This review aims to explore the link between ncRNA dysregulation and amyotrophic lateral sclerosis (ALS), the most frequent motoneuron (MN) disorder in adults. Notably, defective RNA metabolism is known to be largely associated with this pathology, which is often regarded as an RNA disease. We also discuss the potential role that these transcripts may play as diagnostic biomarkers and therapeutic targets.

scholarly journals Expression pattern and potential role of Nanos3 in regulating testosterone biosynthesis in Leydig cells of sheep

2020 ◽  
Vol 154 ◽  
pp. 31-42
Author(s):  
Jie Zhao ◽  
Hua Yang ◽  
Mingtian Deng ◽  
Jianyu Ma ◽  
Zhibo Wang ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Leydig Cells ◽  
Potential Role ◽  
Testosterone Biosynthesis

scholarly journals CRISPR/Cas9-mediated genome-edited mice reveal 10 testis-enriched genes are dispensable for male fecundity

2020 ◽  
Vol 103 (2) ◽  
pp. 195-204
Author(s):  
Soojin Park ◽  
Keisuke Shimada ◽  
Yoshitaka Fujihara ◽  
Zoulan Xu ◽  
Kentaro Shimada ◽  
...  
Keyword(s):  
Protein Function ◽  
Male Fertility ◽  
System Analysis ◽  
In Silico Analysis ◽  
Male Reproduction ◽  
Hormonal Contraceptives ◽  
World Population ◽  
Functional Screening ◽  
Mouse Lines

Abstract As the world population continues to increase to unsustainable levels, the importance of birth control and the development of new contraceptives are emerging. To date, male contraceptive options have been lagging behind those available to women, and those few options available are not satisfactory to everyone. To solve this problem, we have been searching for new candidate target proteins for non-hormonal contraceptives. Testis-specific proteins are appealing targets for male contraceptives because they are more likely to be involved in male reproduction and their targeting by small molecules is predicted to have no on-target harmful effects on other organs. Using in silico analysis, we identified Erich2, Glt6d1, Prss58, Slfnl1, Sppl2c, Stpg3, Tex33, and Tex36 as testis-abundant genes in both mouse and human. The genes, 4930402F06Rik and 4930568D16Rik, are testis-abundant paralogs of Glt6d1 that we also discovered in mice but not in human, and were also included in our studies to eliminate the potential compensation. We generated knockout (KO) mouse lines of all listed genes using the CRISPR/Cas9 system. Analysis of all of the individual KO mouse lines as well as Glt6d1/4930402F06Rik/4930568D16Rik TKO mouse lines revealed that they are male fertile with no observable defects in reproductive organs, suggesting that these 10 genes are not required for male fertility nor play redundant roles in the case of the 3 Glt6D1 paralogs. Further studies are needed to uncover protein function(s), but in vivo functional screening using the CRISPR/Cas9 system is a fast and accurate way to find genes essential for male fertility, which may apply to studies of genes expressed elsewhere. In this study, although we could not find any potential protein targets for non-hormonal male contraceptives, our findings help to streamline efforts to find and focus on only the essential genes.

scholarly journals Role of Selective Autophagy in Spermatogenesis and Male Fertility

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2523
Author(s):  
Chunyu Lv ◽  
Xiaoli Wang ◽  
Ying Guo ◽  
Shuiqiao Yuan
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Genetic Regulation ◽  
Underlying Mechanism ◽  
Intracellular Pathogens ◽  
Selective Autophagy ◽  
Reproductive Processes ◽  
Infertile Patients ◽  
Shed Light

Autophagy is a “self-eating” process that engulfs cellular contents for their subsequent digestion in lysosomes to engage the metabolic need in response to starvation or environmental insults. According to the contents of degradation, autophagy can be divided into bulk autophagy (non-selective autophagy) and selective autophagy. Bulk autophagy degrades non-specific cytoplasmic materials in response to nutrient starvation while selective autophagy targets specific cargoes, such as damaged organelles, protein aggregates, and intracellular pathogens. Selective autophagy has been documented to relate to the reproductive processes, especially for the spermatogenesis, fertilization, and biosynthesis of testosterone. Although selective autophagy is vital in the field of reproduction, its role and the underlying mechanism have remained unclear. In this review, we focus on selective autophagy to discuss the recent advances in our understanding of the mechanism and role of selective autophagy on spermatogenesis and male fertility in mammals. Understanding the role of selective autophagy during spermatogenesis will promote the recognition of genetic regulation in male infertility, and shed light on therapies of infertile patients.

scholarly journals Endocrine regulation of circadian physiology

2016 ◽  
Vol 230 (1) ◽  
pp. R1-R11 ◽  
Author(s):  
Anthony H Tsang ◽  
Mariana Astiz ◽  
Maureen Friedrichs ◽  
Henrik Oster
Keyword(s):  
Potential Role ◽  
Current Knowledge ◽  
Endocrine System ◽  
Endocrine Regulation ◽  
Biological Processes ◽  
Endogenous Rhythmicity ◽  
Circadian Physiology ◽  
External Time ◽  
High Calorie

Endogenous circadian clocks regulate 24-h rhythms of behavior and physiology to align with external time. The endocrine system serves as a major clock output to regulate various biological processes. Recent findings suggest that some of the rhythmic hormones can also provide feedback to the circadian system at various levels, thus contributing to maintaining the robustness of endogenous rhythmicity. This delicate balance of clock–hormone interaction is vulnerable to modern lifestyle factors such as shiftwork or high-calorie diets, altering physiological set points. In this review, we summarize the current knowledge on the communication between the circadian timing and endocrine systems, with a focus on adrenal glucocorticoids and metabolic peptide hormones. We explore the potential role of hormones as systemic feedback signals to adjust clock function and their relevance for the maintenance of physiological and metabolic circadian homeostasis.

scholarly journals Aromatase, oestrogens and human male reproduction

2010 ◽  
Vol 365 (1546) ◽  
pp. 1571-1579 ◽  
Author(s):  
Serge Carreau ◽  
Slaweck Wolczynski ◽  
Isabelle Galeraud-Denis
Keyword(s):  
Leydig Cells ◽  
Single Gene ◽  
Mammalian Species ◽  
Male Reproduction ◽  
Biologically Active ◽  
Human Male ◽  
Final Maturation ◽  
Polymerase Chain ◽  
High Degree

In most mammalian species aromatase is encoded by a single gene ( Cyp19 ), which contains 18 exons, nine of them being translated. In man, the presence of a biologically active aromatase and oestrogen receptors (ERα and ERβ) has been reported in Leydig cells, and also in immature germ cells and ejaculated spermatozoa. Concerning aromatase, the amount of transcript and enzymatic activity are decreased in immotile compared with motile sperm. We have amplified aromatase mRNA by real-time polymerase chain reaction in spermatozoa from asthenospermic, teratospermic and asthenoteratospermic men and recorded, respectively, 44, 52 and 67 per cent decreases of the amount of transcripts compared with fertile donors. A high degree of correlation ( r = −0.64) between the abnormal spermatozoa (especially microcephaly and acrosome malformations) and aromatase/GAPDH transcript ratio has been observed. Idiopathic infertility is a wide health problem and no treatment is currently available. In humans, even if the role of oestrogens in spermatogenesis is still a matter of debate, the observations of decreased sperm number and motility in men genetically deficient in aromatase, together with our data and those reported in the literature, may suggest a role for aromatase/oestrogens not only during the development and maintenance of spermatogenesis but also in the final maturation of spermatozoa.

Ablation of adipose-HO-1 expression increases white fat over beige fat through inhibition of mitochondrial fusion and of PGC1α in female mice

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Shailendra P. Singh ◽  
Ilana Grant ◽  
Aliza Meissner ◽  
Attallah Kappas ◽  
Nader G. Abraham
Keyword(s):  
Adipose Tissue ◽  
Knockout Mouse ◽  
Potential Role ◽  
Mitochondrial Quality Control ◽  
Knockout Mouse Model ◽  
Genetic Ablation ◽  
Beige Fat ◽  
And Function ◽  
White Fat

AbstractBackgroundHmox1 plays an important role in the regulation of mitochondrial bioenergetics and function by regulating cellular heme-derived CO and bilirubin. Previous studies have demonstrated that global disruption of HO-1 in humans and mice resulted in severe organ dysfunction.MethodsWe investigated the potential role of adipose-specific-HO-1 genetic ablation on adipose tissue function, mitochondrial quality control and energy expenditure by generating an adipo-HO-1 knockout mouse model (Adipo-HO-1ResultsAdipo-HO-1ConclusionAblation of adipose tissue-HO-1 abridged PGC1 expression promoted mitochondrial dysfunction and contributed to an increase of pro-inflammatory visceral fat and abrogated beige-cell like phenotype.

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