scholarly journals Biomechanics of Early Life in the Female Reproductive Tract

Physiology ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 134-143 ◽  
Author(s):  
David Elad ◽  
Ariel J. Jaffa ◽  
Dan Grisaru
Keyword(s):  
Early Life ◽  
Reproductive Tract ◽  
Human Life ◽  
Uterine Wall ◽  
Female Reproductive Tract ◽  
In Vivo Studies ◽  
Successful Pregnancy ◽  
Early Human

Early human life that starts at the onset of fertilization and ends with implantation of the embryo in the uterine wall is the foundation for a successful pregnancy. The different stages during this period require biomechanical mechanisms, which are mostly unknown due to difficulties to conduct in vivo studies in humans.

scholarly journals Vitamin D3 Controls TLR4- and TLR2-Mediated Inflammatory Responses of Endometrial Cells

2021 ◽  
pp. 1-10
Author(s):  
Alireza Ghanavatinejad ◽  
Nesa Rashidi ◽  
Mahroo Mirahmadian ◽  
Simin Rezania ◽  
Mahdokht Mosalaei ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Female Reproductive Tract ◽  
In Vivo Studies ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Tnf Α ◽  
Tract Infections

<b><i>Objectives:</i></b> Vitamin D has potent immunoregulatory features and modulates innate and adaptive immune responses. There is a significant association between intrauterine infection-associated inflammatory responses and pregnancy complications such as abortion and preterm labor. Here, we investigated how 1,25 (OH)2 D3 could modulate inflammatory responses of endometrial cells. <b><i>Design:</i></b> This is an in vitro experimental study. Endometrial stromal cells (ESCs) and whole endometrial cells (WECs) were collected from 15 apparently normal women, and the immunomodulatory effects of 1,25 (OH)2 D3 on lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated ESCs and WECs were investigated. <b><i>Participants/Materials, Setting, and Methods:</i></b> Women with no history of abortion, infertility, endometriosis, or sign of vaginal infection were enrolled in this study. Endometrial samples were collected by gynecologists using a Pipelle pipette in the proliferative phase of the menstrual cycle. WECs and ESCs were collected and treated with either LPS or LTA. The levels of IL-6, IL-8, and TNF-α in culture supernatants were quantified using the ELISA technique. TLR2, TLR4, and MyD88 expressions were assessed by RT-qPCR. TLR4 expression at the protein level was studied by the Western blot technique. <b><i>Results:</i></b> 1,25 Dihydroxycholecalciferol (1,25 (OH)2 D3) significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pretreatment increased the production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pretreatment markedly reduced LPS-induced TLR4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pretreated with 1,25 (OH)2 D3 before stimulation with LPS. <b><i>Limitations:</i></b> Because of the small size of samples, doing experiments all together on some samples was not feasible. Confirmation of the results obtained here needs well-designed in vivo studies. <b><i>Conclusions:</i></b> 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintaining endometrial immune homeostasis by controlling potentially harmful inflammatory responses associated with female reproductive tract infections.

scholarly journals Exosomes Transport Anti-Human Immunodeficiency Virus Factors from Human Cervical Epithelial Cells to Macrophages

2021 ◽  
pp. 1-11
Author(s):  
Xi-Qiu Xu ◽  
Biao Zhang ◽  
Le Guo ◽  
Yu Liu ◽  
Feng-Zhen Meng ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Hiv Infection ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Female Reproductive Tract ◽  
In Vivo Studies ◽  
Cervical Epithelial Cells ◽  
Anti Hiv

The female reproductive tract (FRT) is a major site of HIV sexual transmission. As the outermost layer of cells in the FRT, the human cervical epithelial cells (HCEs) have direct contact with HIV or infected cells. Our early work showed that supernatant (SN) from TLR3-activated HCEs contain the antiviral factors that could potently inhibit HIV replication in macrophages. However, it remains to be determined how HCEs transport the anti-HIV factors to macrophages. This follow-up study examined the role of exosomes in HCE-mediated anti-HIV activity. We found that TLR3 activation of HCEs resulted in the release of exosomes that contained multiple IFN-stimulated genes (ISGs: <i>ISG56</i>, <i>OAS1</i>, <i>MxA,</i> and <i>Mx2</i>) and the HIV restriction microRNAs (miR-28, miR-29 family members, miR-125b, miR-150, miR-382, miR-223, miR-20a, and miR-198). The depletion of exosomes from SN of TLR3-activated HCEs diminished HCE-mediated anti-HIV activity in macrophages, indicating that HCE-derived exosomes are responsible for transporting the antiviral molecules to macrophages. These in vitro findings suggest a novel antiviral mechanism by which HCEs participate in the FRT innate immunity against HIV infection. Further in vivo studies are necessary in order to develop an exosome-based delivery system for prevention and treatment of HIV infection through sexual transmission.

scholarly journals Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm capacitation

Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Naoya Araki ◽  
Natsuko Kawano ◽  
Woojin Kang ◽  
Kenji Miyado ◽  
Kaoru Yoshida ◽  
...  
Keyword(s):  
Seminal Vesicle ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
The Other ◽  
Sperm Capacitation ◽  
Other Hand ◽  
Sperm Membrane ◽  
Vesicle Secretion ◽  
Mammalian Spermatozoa

Mammalian spermatozoa acquire their fertilizing ability in the female reproductive tract (sperm capacitation). On the other hand, seminal vesicle secretion, which is a major component of seminal plasma, inhibits the initiation of sperm capacitation (capacitation inhibition) and reduces the fertility of the capacitated spermatozoa (decapacitation). There are seven major proteins involved in murine seminal vesicle secretion (SVS1-7), and we have previously shown that SVS2 acts as both a capacitation inhibitor and a decapacitation factor, and is indispensable forin vivofertilization. However, the effects of SVSs other than SVS2 on the sperm have not been elucidated. Since mouseSvs2–Svs6genes evolved by gene duplication belong to the same gene family, it is possible that SVSs other than SVS2 also have some effects on sperm capacitation. In this study, we examined the effects of SVS3 and SVS4 on sperm capacitation. Our results showed that both SVS3 and SVS4 are able to bind to spermatozoa, but SVS3 alone showed no effects on sperm capacitation. On the other hand, SVS4 acted as a capacitation inhibitor, although it did not show decapacitation abilities. Interestingly, SVS3 showed an affinity for SVS2 and it facilitated the effects of SVS2. Interaction of SVS2 and spermatozoa is mediated by the ganglioside GM1 in the sperm membrane; however, both SVS3 and SVS4 had weaker affinities for GM1 than SVS2. Therefore, we suggest that separate processes may cause capacitation inhibition and decapacitation, and SVS3 and SVS4 act on sperm capacitation cooperatively with SVS2.

scholarly journals Opening the black box: Stem cell–based modeling of human post-implantation development

2018 ◽  
Vol 218 (2) ◽  
pp. 410-421 ◽  
Author(s):  
Kenichiro Taniguchi ◽  
Idse Heemskerk ◽  
Deborah L. Gumucio
Keyword(s):  
Stem Cell ◽  
Human Development ◽  
Experimental Models ◽  
Uterine Wall ◽  
Black Box ◽  
Cellular Mechanisms ◽  
Early Human Development ◽  
Post Implantation ◽  
Early Human

Proper development of the human embryo following its implantation into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)–based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development.

scholarly journals RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qin Yu ◽  
Jianzhang Wang ◽  
Tiantian Li ◽  
Xinxin Xu ◽  
Xinyue Guo ◽  
...  
Keyword(s):  
Nude Mice ◽  
Reproductive Tract ◽  
Epithelial Mesenchymal Transition ◽  
Endometrial Adenocarcinoma ◽  
Female Reproductive Tract ◽  
Migration And Invasion ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d’origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

scholarly journals Proteomics and metabolomics in cow fertility: a systematic review

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. 639-658
Author(s):  
Nicolas Aranciaga ◽  
James D Morton ◽  
Debra K Berg ◽  
Jessica L Gathercole
Keyword(s):  
Oxidative Stress ◽  
Systematic Review ◽  
Large Scale ◽  
Reproductive Tract ◽  
Early Embryo ◽  
Female Reproductive Tract ◽  
Full Potential ◽  
Technical Standards ◽  
The Impact

Cow subfertility is a multi-factorial problem in many countries which is only starting to be unravelled. Molecular biology can provide a substantial source of insight into its causes and potential solutions, particularly through large scale, untargeted omics approaches. In this systematic review, we set out to compile, assess and integrate the latest proteomic and metabolomic research on cow reproduction, specifically that on the female reproductive tract and early embryo. We herein report a general improvement in technical standards throughout the temporal span examined; however, significant methodological limitations are also identified. We propose easily actionable avenues for ameliorating these shortcomings and enhancing the reach of this field. Text mining and pathway analysis corroborate the relevance of proteins and metabolites related to the triad oxidative stress-inflammation-disease on reproductive function. We envisage a breakthrough in cattle reproductive molecular research within the next few years as in vivo sample techniques are improved, omics analysis equipment becomes more affordable and widespread, and software tools for single- and multi-omics data processing are further developed. Additional investigation of the impact of local oxidative stress and inflammation on fertility, both at the local and systemic levels, is key towards realising the full potential of this field.

scholarly journals CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jean-Ju Chung ◽  
Kiyoshi Miki ◽  
Doory Kim ◽  
Sang-Hee Shim ◽  
Huanan F Shi ◽  
...  
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Targeted Disruption ◽  
Vitro Fertilization ◽  
Male Subfertility ◽  
Epididymal Spermatozoa ◽  
Mammalian Female ◽  
Signaling Domains

We report that the Gm7068 (CatSpere) and Tex40 (CatSperz) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of CatSperz reduces CatSper current and sperm rheotactic efficiency in mice, resulting in severe male subfertility. Normally distributed in linear quadrilateral nanodomains along the flagellum, the complex lacking CatSperζ is disrupted at ~0.8 μm intervals along the flagellum. This disruption renders the proximal flagellum inflexible and alters the 3D flagellar envelope, thus preventing sperm from reorienting against fluid flow in vitro and efficiently migrating in vivo. Ejaculated CatSperz-null sperm cells retrieved from the mated female uterus partially rescue in vitro fertilization (IVF) that failed with epididymal spermatozoa alone. Human CatSperε is quadrilaterally arranged along the flagella, similar to the CatSper complex in mouse sperm. We speculate that the newly identified CatSperζ subunit is a late evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract.

301 THE EFFECT OF EQUINE FOLICULLAR FLUID ON IN VITRO INDUCTION OF THE ACROSOME REACTION IN FROZEN - THAWED STALLION SPERMATOZOA

2010 ◽  
Vol 22 (1) ◽  
pp. 307
Author(s):  
D. S. Silva ◽  
P. Rodriguez ◽  
N. S. Arruda ◽  
R. Rodrigues ◽  
J. L. Rodrigues
Keyword(s):  
Contact Area ◽  
Follicular Fluid ◽  
Acrosome Reaction ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Heparin Group ◽  
Fluorescent Stain ◽  
In Vitro Induction

The capacitation process occurs in vivo upon exposure of the spermatozoa through the female reproductive tract, but can be induced in vitro in the presence of several compounds. This study was conducted to assess the effect of heparin or equine follicular fluid on hyperactivated motility and in vitro induction acrosome reaction swim-up method with frozen-thawed stallion semen. Two hundred microliters of frozen-thawed equine semen was placed in a tube (45°C) to increase contact area and incubated at 37°C for 1 h. After incubation 800 μL of the supernatant was collected by centrifugation (500 × g, 10 min) to collect spermatozoa. The resulting pellet was resuspended in capacitation medium Fert-TALP supplemented with 5.0 μg mL-1 heparin or 100% follicular fluid and incubated for different times (1, 2, 3, 4, and 5 h) at 37°C. After incubation the hyperactivated motility and acrosome-reacted spermatozoa were evaluated. Hoechst stain was used to differentiate live and dead spermatozoa, and chlortetracycline (CTC) fluorescent stain was used to assess the capacitation response of sperm; data were analyzed by ANOVA. The effect of equine follicular fluid resulted in improved percentage of spermatozoa with acrosome reaction at all times of incubation (60, 63, 57, 52, and 58%) but immediately after 3 h of incubation, the hyperactivated motility decreased in heparin group and follicular fluid (42 and 30%, respectively).

scholarly journals ESR1 Mutations Associated With Estrogen Insensitivity Syndrome Change Conformation of Ligand-Receptor Complex and Altered Transcriptome Profile

Endocrinology ◽  
2020 ◽  
Vol 161 (6) ◽  
Author(s):  
Yin Li ◽  
Katherine J Hamilton ◽  
Lalith Perera ◽  
Tianyuan Wang ◽  
Artiom Gruzdev ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Biological Effects ◽  
Estrogen Receptor Α ◽  
Female Reproductive Tract ◽  
Receptor Complexes ◽  
Esr1 Gene ◽  
Esr1 Mutations

Abstract Estrogen insensitivity syndrome (EIS) arises from rare mutations in estrogen receptor-α (ERα, encoded by ESR1 gene) resulting in the inability of estrogen to exert its biological effects. Due to its rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. Here, we investigate known ESR1 mutants, Q375H and R394H, associated with EIS patients using in vitro and in vivo systems. Comparison of the transcriptome and deoxyribonucleic acid methylome from stable cell lines of both Q375H and R394H clinical mutants shows a differential profile compared with wild-type ERα, resulting in loss of estrogen responsiveness. Molecular dynamic simulation shows that both ESR1 mutations change the ERα conformation of the ligand-receptor complexes. Furthermore, we generated a mouse model Esr1-Q harboring the human mutation using CRISPR/Cas9 genome editing. Female and male Esr1-Q mice are infertile and have similar phenotypes to αERKO mice. Overall phenotypes of the Esr1-Q mice correspond to those observed in the patient with Q375H. Finally, we explore the effects of a synthetic progestogen and a gonadotropin-releasing hormone inhibitor in the Esr1-Q mice for potentially reversing the impaired female reproductive tract function. These findings provide an important basis for understanding the molecular mechanistic consequences associated with EIS.

scholarly journals Practical Applications of Sperm Selection Techniques as a Tool for Improving Reproductive Efficiency

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
J. M. Morrell ◽  
H. Rodriguez-Martinez
Keyword(s):  
Hyaluronic Acid ◽  
Reproductive Tract ◽  
Sex Selection ◽  
Female Reproductive Tract ◽  
Sperm Selection ◽  
Domestic Species ◽  
Practical Applications ◽  
Selection For ◽  
Hyaluronic Acid Binding

Modern biotechnologies are used extensively in the animal breeding industry today. Therefore, it is essential that sperm handling procedures do not modulate the normal physiological mechanisms occurring in the female reproductive tract. In this paper, the different selection mechanisms occurringin vivoare described briefly, together with their relevance to artificial insemination, followed by a detailed description of the different selection processes used in reproductive biotechnologies. These selection methods included fractionated semen collection, cryopreservation, biomimetic sperm selection, selection based on hyaluronic acid binding, and last, but not least, sperm sex selection. Biomimetic sperm selection for AI or for cryopreservation could improve pregnancy rates and help to reverse the decline in fertility seen in several domestic species over the recent decades. Similarly, selection for hyaluronic acid binding sites may enable the most mature spermatozoa to be selected for IVF or ICSI.

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