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 ◽  
...  

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.

2019 ◽  
Author(s):  
Jovino C. Cardoso ◽  
Jose M. C. Ribeiro ◽  
Daniela V. dos Santos ◽  
Marcos H. Pereira ◽  
Ricardo N. Araújo ◽  
...  

AbstractRhodnius prolixus is amongst the most important vectors of Trypanosoma cruzi in the Americas, putting thousands of people at risk of contracting Chagas Disease. This insect is also one of the most important models in insect physiology, especially regarding the blood-feeding process. However, studies on R. prolixus genetics lagged, and our understanding on the regulation of gene expression is incipient. Transcriptomes have the power to study the expression of thousands of genes in a single experiment. A comprehensive R. prolixus transcriptome was performed in 2014, sequencing RNA from different tissues (anterior gut, midgut, posterior gut, rectum, ovaries, fat body, maphigian tubules, and testicles). However, on that occasion, only the gut transcriptome was deeply analysed. Here we evaluated the results of the testicles transcriptome of R. prolixus with the objective to find and understand genes that could have an important role in male reproduction. We found, that from the 25,673 transcripts assembled in the whole transcriptome, 5,365 have a testicle specific expression pattern. As expected, amongst the most abundant families of transcripts, are those related to spermatogenesis and male fertility, such as myosins, actins, and dyneins. To our surprise, lipocalins, serine protease inhibitors (serpins), and lysozymes also were highly abundant in testicles. The role of these classes of genes are well known in other tissues, such as salivary glands and gut, but very little is known on their role in male reproduction (and we proposed here a few hypothesis that could be tested to address the role of these genes in male fertility). It would be interesting to study further the role of these genes on R. prolixus male fertility. Finally, as a reflection of the lack of knowledge on triatomine genetics, we found that almost half of the transcripts in R. prolixus testicles have no similarities to any other genes on reference databases. Our study shows that we still have a lot to know and to understand about reproduction in triatomine, especially in males. Besides the large number of genes without described function (possibly novel genes), there are those in which the function is known for other tissues, and we can only guess, at best, the role and importance of such genes for triatomine male fertility.Author SummaryThe understanding of the biology of insect’s vectors of parasitic diseases is key to the development of strategies of public health. For decades, the studies on the biology of male insects’ vectors of diseases was neglected, since in many cases female insects are those with relevant role in the spread of diseases. With the development of genomics, large scale studies to compare differential gene expression (transcriptomics) among different tissues, developmental stages, and sex became accessible. In this study, we looked at the physiology of the male reproductive organs of the vector of Chagas disease Rhodnius prolixus. This is a first glimpse, from a perspective of genes differentially expressed in male gonads, in such insects. We also performed an effort to link all identified genes with the insect genome published in 2015. We found ~14,000 genes expressed in the testicles, from which 5,635 genes are expressed exclusively in male reproductive organs. From the ~14,000 genes, we were able to attribute putative biological functions to 6,372 genes, which allowed us to draw a bigger picture on how these genes contribute to male fertility. This study now opens the door for further in-depth studies to find key genes for R. prolixus reproductive biology.


Development ◽  
2021 ◽  
Author(s):  
Na Liu ◽  
Fatimunnisa Qadri ◽  
Hauke Busch ◽  
Stefanie Huegel ◽  
Gabin Sihn ◽  
...  

Spermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear localization of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis including incomplete sperm maturation and massive loss of sperms that are accompanied by disturbed histone-protamine-exchange, differential localization of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.


2020 ◽  
Author(s):  
Na Liu ◽  
Fatimunnisa Qadri ◽  
Hauke Busch ◽  
Stefanie Huegel ◽  
Gabin Sihn ◽  
...  

AbstractSpermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin α7 in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin α7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by disturbed histone-protamine-exchange, absence of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes, resulting in incomplete sperm maturation and massive loss of sperms. Our work uncovers the essential role of importin α7 in spermatogenesis and hence in male fertility.


Author(s):  
Nabil A. Khouri ◽  
Haytham M. Daradka ◽  
Mohammed Z. Allouh ◽  
Ahmad S. Alkofahi

Abstract: The effects of: Both plants were administered orally to two separate mice groups at a dose of 800 mg/kg/day for 35 days and compared with control group. After treatment, 5 mice of each group were sacrificed and total mice weights, reproductive organs’ weights, spermatogenesis, and androgenic serum markers were investigated. The remaining mice from all groups were allowed to mate with virgin female mice to explore male fertility potential.: Results indicated that body and organs’ weights were increased significantly in mice treated with: We can conclude that


2009 ◽  
Vol 21 (9) ◽  
pp. 113
Author(s):  
A. Drummond ◽  
I. Kuyznierewicz ◽  
P. J. Fuller

Nuclear factor-κB (NF-κB) designates a family of transcription factors that have been shown to modulate antiviral, inflammatory and immune responses. Activation of NF-κB is dependent on IKKβ a component of the IκB kinase (IKK) complex which promotes degradation of IκB inhibitory proteins and allows nuclear translocation of NF-κB. Our studies in ovarian granulosa cell tumour cell lines (COV434 and KGN) indicate that NF-κB signalling is constitutively activated. FSH has been reported to increase XIAP expression through NFκB activity in granulosa cells, but beyond that the role of NFκB signalling in folliculogenesis has not been elucidated. To establish the significance of NF-κB signalling in the ovary (and testis), we have generated a gonadal specific IKKbeta conditional knockout mouse. A transgenic mouse line containing floxed IKKβ alleles (gift of M Karin, UCSD) was crossed with a cre mouse line (gift of M Matzuk, BCM) expressing the recombinase in anti-Müllerian hormone receptor expressing cells (granulosa cells or Sertoli cells). The resulting mice will not express IKKβ in granulosa cells or Sertoli cells and thus cannot activate the classical NFκB signalling pathway. On histological assessment, the ovaries and testes from flox x cre (heterogenous) mice appear normal with follicles of all developmental stages and corpora lutea. Preliminary data suggests that breeding with the heterogenous females resulted in increased litter sizes. The histology of the testes is also unremarkable. The mice homozygous for the deletion of IKKβ in the granulosa cells appear healthy and a preliminary assessment does not reveal gross morphological abnormalities of the ovaries. The results of detailed histological and overall assessment of these mice will be presented. These IKK conditional knockout mice should provide insights into the role of NFκB signalling in gonadal function.


Author(s):  
S. K. Bhure ◽  
P. Harikrishna ◽  
J. Usharani ◽  
A. M. Shende ◽  
S. Harikumar

Regucalcin is a multifunctional protein having an important role in calcium homeostasis, L-ascorbic acid biosynthesis, anti-prolific, anti-apoptotic functions as well as detoxification of chemical warfare nerve agents. Recently, it has been localized to male reproductive tract of rat and human, and identified as an androgen-target gene. The literature suggests a possible role of regucalcin in male fertility. However, no detailed studies have been conducted on its role in male reproductive organs of domestic animals. As an initial step, we had cloned and expressed regucalcin in Pichia pastoris. The sequence analysis showed 100% homology with regucalcin of Bos tours both at nucleotide and amino acid level. The SDS-PAGE and Western blot studies of recombinant protein probed with anti-regucalcin monoclonal antibody showed a higher molecular weight (56 kDa) than the expected (35.5 kDa) that could be due to hyperglycosylation. The recombinant regucalcin and its antibodies can be used to study the detailed role of the protein in male reproduction.


2010 ◽  
Vol 21 (5) ◽  
pp. 704-711 ◽  
Author(s):  
Elisa Ciraolo ◽  
Fulvio Morello ◽  
Robin M. Hobbs ◽  
Frieder Wolf ◽  
Romina Marone ◽  
...  

Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.


2018 ◽  
Vol 28 (1) ◽  
pp. 13
Author(s):  
Hasbi Hasbi ◽  
Sri Gustina

<p class="00-6Abstrak2Wtz">Male fertility is affected by quantity and quality of sperm which controlled by androgens (testosterone and 5α-dihydrotestosterone) mediated by androgen receptors (AR). Androgen receptors belong to receptor group of steroid hormone and a group of ligand-activated nuclear receptor superfamily. This paper explains androgen hormone and its regulation in spermatogenesis to increase male fertility. Regulation of androgen hormone in spermatogenesis include initiation of spermatogenesis, proliferation and maturation of Sertoli cells, germ cell development, spermatogonia, meiosis, and spermiogenesis. The role of androgen hormone in regulation of spermatogenesis is influenced by AR, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. Disruption of spermatogenesis will cause low male fertility. However, low concentrations of AR, LH and FSH could be enhanced by exogenous gonadotrophine releasing hormone (GnRH), LH, FSH, and testosterone to increase male fertility.</p>


2021 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  

AbstractThe sperm flagellum is essential for male fertility. Despite vigorous research progress towards understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. The disruption of Cfap53 decreased the expression level of these two proteins and disrupted their localization in spermatids. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with MMAF.


1991 ◽  
Vol 128 (3) ◽  
pp. 395-401 ◽  
Author(s):  
T. Iguchi ◽  
Y. Uesugi ◽  
N. Takasugi ◽  
V. Petrow

ABSTRACT The role of 5α-dihydrotestosterone (DHT) in the development of the genital organs and in the differentiation of the genital tract into prostate, coagulating gland (CG), bulbo-urethral gland (BUG) and seminal vesicle (SV) in male mice exposed prenatally to the 5α-reductase inhibitor 6-methylene-4-pregnene-3,20-dione (6-MP) has been examined quantitatively. Female ICR mice were given 7 daily s.c. injections of the inhibitor (400 mg/day) starting on day 12 of gestation and the experiment was terminated on day 19 when the fetuses were removed by Caesarian section. In the prenatally 6-MP-exposed male mice the anogenital distance was significantly shorter than in the controls. Feminization of the nipples and hypospadias of the phallic urethra were noted. Development of prostate, CG and BUG was significantly suppressed. SV and testis development were not affected. These results lend further support to the conclusion that DHT is necessary for the development of the urogenital sinus (prostate, CG and BUG) and penis, and for the regression of the nipples in male mice. Reproductive abnormalities were not found in 90-day-old mice of both sexes exposed to 6-MP in utero. The 6-MP-exposed male and female mice had a normal reproductive capacity when mated with normal mice. These results show that 6-MP-induced growth retardation of reproductive organs is evident on day 19 of gestation, but that such retardation is no longer apparent in the adult. Journal of Endocrinology (1991) 128, 395–401


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