Sperm Biology and Reproductive Health

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 20 July 2024 | Viewed by 8515

Special Issue Editors


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Guest Editor
State Key Laboratory of Stem Cell and Reproduction Biology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China
Interests: SSCs differentiation; mammalian oocytes; gonadal biology

E-Mail Website
Guest Editor
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100006, China
Interests: SSCs differentiation; mammalian oocytes; somatic cell clone; innate immunity
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Special Issue Information

Dear Colleagues,

According to the World Health Organization, the global fertility rate has continued to decline over the past 50 years. About 10% to 15% of couples of childbearing ages are infertile; half of them attribute this to "male factors", and 70–90% of male infertility is due to spermatogenic disorders. Endogenous damaging factors, environmental factors, bacteria and viruses, radiotherapy and chemotherapy, etc., will hinder spermatogenesis and prevent spermatogenesis in the body. Spermatogonial stem cells can self-renew and differentiate into sperm. An ideal solution is to use seed cells (SSC) to induce differentiation in vitro to obtain sperm, and then to obtain individual samples by single sperm injection. Scientists have obtained rat functional sperm by testicular tissue culture; however, the efficiency of differentiation in vitro is low, and the differentiation system is still imperfect. The main reason is that the differentiation mechanism of SSCs is still unclear. Spermatogenesis is a complex process that undergoes mitosis, meiosis and spermiogenesis. At present, the molecular and cellular mechanisms in spermatogenesis are not completely clear. Exploring the mechanism of spermatogenesis, optimizing the round sperm injection system and finally obtaining individuals can improve the assisted reproductive system based on round sperm.

This topic will discuss the mechanism of spermatogenesis, the treatment of male infertility (non-obstructive azoospermia (NOA)), and the preservation of male fertility (pre-adolescent cancer patients who are facing infertility due to cancer treatment, patients who have received radiotherapy and chemotherapy).

Prof. Yi-Xun Liu
Dr. Shou-Long Deng
Guest Editors

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Keywords

  • spermatogenesis
  • differentiation of spermatogonial stem cells in vitro
  • mitosis
  • meiosis
  • sperm formation

Published Papers (5 papers)

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Research

17 pages, 9202 KiB  
Article
TTC6-Mediated Stabilization of the Flagellum Annulus Ensures the Rapid and Directed Motion of Sperm
by Ziqi Wang, Kailun Fang, Yanling Wan, Yingying Yin, Mengjing Li, Ke Xu, Tongtong Li, Yongzhi Cao, Yue Lv, Gang Lu, Hongbin Liu and Tao Huang
Cells 2023, 12(16), 2091; https://doi.org/10.3390/cells12162091 - 18 Aug 2023
Viewed by 988
Abstract
Sperm motility and structural integrity are essential for successful fertilization in vivo, and any hindrance of the correct assembly of the axoneme and peri-axonemal structures in the sperm flagellum can lead to fertility problems. While there has been considerable advancement in studying diseases [...] Read more.
Sperm motility and structural integrity are essential for successful fertilization in vivo, and any hindrance of the correct assembly of the axoneme and peri-axonemal structures in the sperm flagellum can lead to fertility problems. While there has been considerable advancement in studying diseases related to the flagellum, the underlying mechanisms that control sperm movement are not yet fully understood. In this study, we reveal that the tetratricopeptide repeat protein 6 (Ttc6) gene, expressed mainly in the testes, plays a crucial role in maintaining male fertility in mice. We further demonstrate that the knockout of Ttc6 in mice results in decreased sperm motility and induces an abnormal circular swimming pattern, consequently leading to male subfertility. Morphological analysis showed an atypical hairpin-like appearance of the spermatozoa, and ultrastructural studies showed unsheathed flagella at the juncture between the midpiece and principal piece. Collectively, these findings suggest that TTC6 plays an essential role in maintaining the stability of the annulus region of the sperm flagellum, thus ensuring the swift and directed motion of sperm. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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15 pages, 2565 KiB  
Article
Deficiency of the Tmem232 Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice
by Xiuqing He, Wenyu Mu, Ziqi Wang, Ke Xu, Yingying Yin, Gang Lu, Wai-Yee Chan, Hongbin Liu, Yue Lv and Shangming Liu
Cells 2023, 12(12), 1614; https://doi.org/10.3390/cells12121614 - 13 Jun 2023
Cited by 2 | Viewed by 1278
Abstract
The axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched [...] Read more.
The axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched gene transmembrane protein 232 (Tmem232), which is essential for the structural integrity of the spermatozoa flagella axoneme. Tmem232 knockout mice were generated for in vivo analyses of its functions in spermatogenesis. Phenotypic analysis showed that deletion of Tmem232 in mice causes male-specific infertility. Transmission electron microscopy together with scanning electron microscopy were applied to analyze the spermatozoa flagella and it was observed that the lack of TMEM232 caused failure of the cytoplasm removal and the absence of the 7th outer microtubule doublet with its corresponding outer dense fiber (ODF). Co-IP assays further identified that TMEM232 interacts with ODF family protein ODF1, which is essential to maintain sperm motility. In conclusion, our findings indicate that TMEM232 is a critical protein for male fertility and sperm motility by regulating sperm cytoplasm removal and maintaining axoneme integrity. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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14 pages, 2457 KiB  
Article
Effect of Poria cocos Mushroom Polysaccharides (PCPs) on the Quality and DNA Methylation of Cryopreserved Shanghai White Pig Spermatozoa
by Jinyong Zhou, Keqin Zhang, Jun Gao, Jiehuan Xu, Caifeng Wu, Mengqian He, Shushan Zhang, Defu Zhang, Jianjun Dai and Lingwei Sun
Cells 2023, 12(11), 1456; https://doi.org/10.3390/cells12111456 - 24 May 2023
Cited by 2 | Viewed by 1374
Abstract
In this study, we explore the effects of Poria cocos mushroom polysaccharides (PCPs) on the quality and DNA methylation of the cryopreserved spermatozoa of Shanghai white pigs. A total of 24 ejaculates (three ejaculate samples per boar) from eight Shanghai white pigs were [...] Read more.
In this study, we explore the effects of Poria cocos mushroom polysaccharides (PCPs) on the quality and DNA methylation of the cryopreserved spermatozoa of Shanghai white pigs. A total of 24 ejaculates (three ejaculate samples per boar) from eight Shanghai white pigs were manually collected. The pooled semen was diluted with a based extender supplemented with different concentrations of PCPs (0, 300, 600, 900, 1200, and 1500 μg/mL). Once thawed, the quality of the spermatozoa and their antioxidant function were assessed. In the meantime, the effect of spermatozoa DNA methylation was also analyzed. The results show that compared with the control group, 600 μg/mL of PCPs significantly improves the spermatozoa viability (p < 0.05). The motility and plasma membrane integrity of the frozen–thawed spermatozoa are significantly higher after treatment with 600, 900, and 1200 μg/mL of PCPs compared with the control group (p < 0.05). In comparison with the control group, the percentages of acrosome integrity and mitochondrial activity are significantly enhanced after the application of 600 and 900 μg/mL PCPs (p < 0.05). The reactive oxygen species (ROS), the malondialdehyde (MDA) levels, and the glutathione peroxidase (GSH-Px) activity, in comparison with the control group, are significantly decreased in all groups with PCPs (all p < 0.05). The enzymatic activity of superoxide dismutase (SOD) in spermatozoa is significantly higher in the treatment with 600 μg/mL of PCPs than in the other groups (p < 0.05). As compared with the control group, a significant increase in the catalase (CAT) level is found in the groups with PCPs at 300, 600, 900, and 1200 μg/mL (all p < 0.05). In comparison with the control group, the 5-methylcytosine (5-mC) levels are significantly decreased in all groups with PCPs (all p < 0.05). As a result of these findings, a certain amount of PCPs (600–900 μg/mL) added to the cryodiluent can significantly improve the quality of Shanghai white pig spermatozoa and can also reduce the methylation of spermatozoa DNA caused by cryopreservation. This treatment strategy may establish a foundation for the cryopreservation of semen from pigs. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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15 pages, 2681 KiB  
Article
Zbtb40 Deficiency Leads to Morphological and Phenotypic Abnormalities of Spermatocytes and Spermatozoa and Causes Male Infertility
by Yinghong Cui, Mingqing Zhou, Quanyuan He and Zuping He
Cells 2023, 12(9), 1264; https://doi.org/10.3390/cells12091264 - 26 Apr 2023
Cited by 3 | Viewed by 1618
Abstract
Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of [...] Read more.
Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of mouse spermatocytes and spermatids as well as male infertility. We revealed that Zbtb40 was expressed in spermatocytes of mouse testes, and it was co-localized with γH2AX in mouse secondary spermatocytes. Interestingly, spermatocytes of Zbtb40 knockout mice had longer telomeres, compromised double-strand break (DSB) repair in the sex chromosome, and a higher apoptosis ratio compared to wild-type (WT) mice. The testis weight, testicular volume, and cauda epididymis body weight of the Zbtb40+/− male mice were significantly lower than in WT mice. Mating tests indicated that Zbtb40+/− male mice were able to mate normally, but they failed to produce any pups. Notably, sperm of Zbtb40+/− mice showed flagellum deformities and abnormal acrosome biogenesis. Furthermore, a ZBTB40 mutation was associated with non-obstructive azoospermia. Our results implicate that ZBTB40 deficiency leads to morphological and phenotypic abnormalities of spermatocytes and spermatids and causes male infertility. This study thus offers a new genetic mechanism regulating mammalian spermatogenesis and provides a novel target for gene therapy in male infertility. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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19 pages, 3960 KiB  
Article
Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments
by Lea Simone Becker, Mohammad A. Al Smadi, Markus Raeschle, Shusruto Rishik, Hashim Abdul-Khaliq, Eckart Meese and Masood Abu-Halima
Cells 2023, 12(7), 1017; https://doi.org/10.3390/cells12071017 - 26 Mar 2023
Cited by 4 | Viewed by 2129
Abstract
Although the proteome of sperm has been characterized, there is still a lack of high-throughput studies on dysregulated proteins in sperm from subfertile men, with only a few studies on the sperm proteome in asthenozoospermic and oligoasthenozoospermic men. Using liquid chromatography–mass spectrometry (LC-MS/MS) [...] Read more.
Although the proteome of sperm has been characterized, there is still a lack of high-throughput studies on dysregulated proteins in sperm from subfertile men, with only a few studies on the sperm proteome in asthenozoospermic and oligoasthenozoospermic men. Using liquid chromatography–mass spectrometry (LC-MS/MS) along with bioinformatics analyses, we investigated the proteomic landscape of sperm collected from subfertile men (n = 22), i.e., asthenozoospermic men (n = 13), oligoasthenozoospermic men (n = 9) and normozoospermic controls (n = 31). We identified 4412 proteins in human sperm. Out of these, 1336 differentially abundant proteins were identified in 70% of the samples. In subfertile men, 32 proteins showed a lower abundance level and 34 showed a higher abundance level when compared with normozoospermic men. Compared to normozoospermic controls, 95 and 8 proteins showed a lower abundance level, and 86 and 1 proteins showed a higher abundance level in asthenozoospermic and oligoasthenozoospermic men, respectively. Sperm motility and count were negatively correlated with 13 and 35 and positively correlated with 37 and 20 differentially abundant proteins in asthenozoospermic and oligoasthenozoospermic men, respectively. The combination of the proteins APCS, APOE, and FLOT1 discriminates subfertile males from normozoospermic controls with an AUC value of 0.95. Combined APOE and FN1 proteins discriminate asthenozoospermic men form controls with an AUC of 1, and combined RUVBL1 and TFKC oligoasthenozoospermic men with an AUC of 0.93. Using a proteomic approach, we revealed the proteomic landscape of sperm collected from asthenozoospermic or oligoasthenozoospermic men. Identified abundance changes of several specific proteins are likely to impact sperm function leading to subfertility. The data also provide evidence for the usefulness of specific proteins or protein combinations to support future diagnosis of male subfertility. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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