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 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 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 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 Perspectives of nanotechnology in male fertility and sperm function

2018 ◽  
Vol 6 (2) ◽  
pp. 265-269 ◽  
Author(s):  
Laura Falchi ◽  
Wael A. Khalil ◽  
Mahmoud Hassan ◽  
Waleed F.A. Marei
Keyword(s):  
Male Fertility ◽  
Sperm Function

scholarly journals The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta‐analysis

Andrology ◽  
2020 ◽  
Author(s):  
Linda Farahani ◽  
Tharu Tharakan ◽  
Tet Yap ◽  
Jonathan W. Ramsay ◽  
Channa N. Jayasena ◽  
...  
Keyword(s):  
Systematic Review ◽  
Male Fertility ◽  
Meta Analysis ◽  
Sperm Function

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.

146 Tributyltin chloride exposure alters ejaculated bull sperm function and embryo development

2020 ◽  
Vol 32 (2) ◽  
pp. 199
Author(s):  
B. W. Daigneault ◽  
K. E. Latham
Keyword(s):  
Embryo Development ◽  
Sperm Motility ◽  
Male Fertility ◽  
The United States ◽  
National Institutes Of Health ◽  
Sperm Function ◽  
Tributyltin Chloride ◽  
Bull Sperm ◽  
Chi Square Analysis ◽  
Motility Parameters

Male exposure to environmental toxicants can disrupt spermatogenesis and impair sperm function. However, the consequences of environmentally relevant levels of toxicants to ejaculated mammalian spermatozoa on sperm function and male fertility are not well studied. Tributyltin chloride (TBT) is an organotin with historical use as an antifouling agent in paints and is a contaminant of soil and groundwater in the United States. Tributyltin chloride is an endocrine disruptor, is detectable in human cord blood, and has negative effects on female reproduction. We hypothesised that TBT could affect sperm function and thereby affect male fertility. To test our hypothesis, we exposed frozen-thawed bull sperm to environmentally relevant doses of TBT (0, 0.1, 1.0, 10, and 100nM) for 90min and then measured sperm motility parameters, fertilisation, and embryo development by IVF. Briefly, frozen-thawed sperm from two bulls were isolated through a 45:90 Percoll gradient, pooled, and then maintained in noncapacitating conditions at 37°C in Tyrode's albumin lactate pyruvate medium devoid of bovine serum albumin and HCO3 − for 90min. Vehicle control (VC) samples consisted of 0.1% MeOH. Sperm motility kinematics were objectively measured after the addition of treatment and every 30min thereafter using computer-aided sperm analysis (IVOS System, Hamilton Thorne). Five replicates were evaluated, and differences in motility kinematics were analysed by analysis of variance using SAS statistical software (SAS Institute Inc.). Sperm treated with 100nM TBT displayed decreased total motility (88 vs. 79%), progressive motility (80 vs. 70%), curvilinear velocity (100 vs. 88 µ/s), and beat-cross frequency (38 vs. 34Hz) over 90min compared with the VC samples (P<0.05). No differences (P>0.05) were detected among any other treatments. Following 90min of exposure to TBT 100nM, sperm were washed twice by centrifugation and re-extended in fertilisation medium. Abattoir-derived bovine oocytes were fertilised with 100nM TBT and VC-exposed sperm. Embryo cleavage and 8- to 16-cell embryos were quantified at 48 and 72h, respectively, in three replicates, and results were assessed using chi-square analysis. Embryos fertilised by TBT-exposed sperm had reduced cleavage to 2-cell (80 vs. 62%) and 8- to 16-cell morulae stages (56 vs. 24%, respectively; P<0.05). In summary, although sperm kinematics were decreased in TBT-exposed sperm, gross motility parameters remained within acceptable ranges for IVF, suggesting that sperm motility alone is not a sufficient measure of sperm function or indicator of male fertility. In conclusion, ejaculated bull sperm exposed to environmentally relevant levels of TBT for 90min had reduced sperm motility parameters, impaired sperm function, and reduced embryo development potential. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number T32HD087166. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

scholarly journals Evolution of the Insulin-Like Growth Factor Binding Protein (IGFBP) Family

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2278-2289 ◽  
Author(s):  
Daniel Ocampo Daza ◽  
Görel Sundström ◽  
Christina A. Bergqvist ◽  
Cunming Duan ◽  
Dan Larhammar
Keyword(s):  
Growth Factor ◽  
Gene Family ◽  
Teleost Fish ◽  
Binding Protein ◽  
Gene Families ◽  
Large Degree ◽  
Sequence Comparisons ◽  
Igf Binding ◽  
Epidermal Growth ◽  
Igf Binding Protein

The evolution of the IGF binding protein (IGFBP) gene family has been difficult to resolve. Both chromosomal and serial duplications have been suggested as mechanisms for the expansion of this gene family. We have identified and annotated IGFBP sequences from a wide selection of vertebrate species as well as Branchiostoma floridae and Ciona intestinalis. By combining detailed sequence analysis with sequence-based phylogenies and chromosome information, we arrive at the following scenario: the ancestral chordate IGFBP gene underwent a local gene duplication, resulting in a gene pair adjacent to a HOX cluster. Subsequently, the gene family expanded in the two basal vertebrate tetraploidization (2R) resulting in the six IGFBP types that are presently found in placental mammals. The teleost fish ancestor underwent a third tetraploidization (3R) that further expanded the IGFBP repertoire. The five sequenced teleost fish genomes retain 9–11 of IGFBP genes. This scenario is supported by the phylogenies of three adjacent gene families in the HOX gene regions, namely the epidermal growth factor receptors (EGFR) and the Ikaros and distal-less (DLX) transcription factors. Our sequence comparisons show that several important structural components in the IGFBPs are ancestral vertebrate features that have been maintained in all orthologs, for instance the integrin interaction motif Arg-Gly-Asp in IGFBP-2. In contrast, the Arg-Gly-Asp motif in IGFBP-1 has arisen independently in mammals. The large degree of retention of IGFBP genes after the ancient expansion of the gene family strongly suggests that each gene evolved distinct and important functions early in vertebrate evolution.

scholarly journals Impact of obesity on male fertility, sperm function and molecular composition

2012 ◽  
Vol 2 (4) ◽  
pp. 253-263 ◽  
Author(s):  
Nicole O. Palmer ◽  
Hassan W. Bakos ◽  
Tod Fullston ◽  
Michelle Lane
Keyword(s):  
Male Fertility ◽  
Molecular Composition ◽  
Sperm Function
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