scholarly journals The Central Role of Cadherins in Gonad Development, Reproduction, and Fertility

2020 ◽  
Vol 21 (21) ◽  
pp. 8264
Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. Kubiak
Keyword(s):  
Germ Cells ◽  
Reproductive Tract ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Gonad Development ◽  
Female Reproductive Tract ◽  
Future Research ◽  
Corpora Lutea ◽  
Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood–testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.

scholarly journals The Central Role of Cadherins in Gonad Development, Reproduction and Fertility

2020 ◽  
Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. KUBIAK
Keyword(s):  
Germ Cells ◽  
Reproductive Tract ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Gonad Development ◽  
Female Reproductive Tract ◽  
Future Research ◽  
Corpora Lutea ◽  
Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.

Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies

2014 ◽  
Vol 128 (3) ◽  
pp. 153-180 ◽  
Author(s):  
Monica Logan ◽  
Shannon M. Hawkins
Keyword(s):  
Reproductive Tract ◽  
Chemotherapy Resistance ◽  
Clinical Information ◽  
Current Data ◽  
Female Reproductive Tract ◽  
Model Systems ◽  
Future Research ◽  
Cancer Type

microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using in vitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract.

scholarly journals Epididymal antimicrobial peptides: the role in sperm function (review)

2021 ◽  
pp. 4-12
Author(s):  
П.А. Шабанов ◽  
О.В. Шамова ◽  
Д.С. Орлов ◽  
А.Ю. Грязнов ◽  
Н.О. Янчук
Keyword(s):  
Antimicrobial Peptides ◽  
Germ Cells ◽  
Plasma Membranes ◽  
Reproductive Tract ◽  
Biological Effects ◽  
Physiological Activity ◽  
Female Reproductive Tract ◽  
Physiological Processes ◽  
Molecular Regulatory Mechanisms

Значительное снижение показателей мужской фертильности, наблюдаемое в последнее время во всем мире, ведёт к необходимости более глубокого изучения механизмов молекулярной регуляции гаметогенеза и посттестикулярной трансформации сперматозоидов. Совершенствование способов влияния на эти процессы, а также поиск веществ, повышающих устойчивость гамет к действию различных повреждающих факторов, открывают перспективы разработки новых подходов в лечении мужского бесплодия. В связи с этим актуальным направлением является исследование роли эндогенных антимикробных пептидов и их физиологической активности при созревании и функционировании мужских половых клеток. Антимикробные пептиды - это уникальные компоненты системы врожденного иммунитета. Они не только обеспечивают противоинфекционную защиту организма от бактерий, вирусов и грибов, но и проявляют достаточно разнообразные биологические эффекты, которые связаны, в том числе и со способностью этих молекул принимать непосредственное участие в физиологических процессах посттестикулярного созревания половых клеток, модификации цитоплазматических мембран сперматозоидов в эпидидимисе, а также капацитации в женском репродуктивном тракте. В настоящем обзоре рассмотрены современные представления о роли антимикробных пептидов придатков яичек с позиций их участия в функционировании сперматозоидов в норме и при патологии. The significant worldwide decline in male fertility requires a comprehensive study of molecular regulatory mechanisms of gametogenesis and post-testicular sperm maturation. Improving ways to influence these processes as well as searching for substances that increase the resistance of gametes to the action of various damaging factors open up prospects for development of new approaches to treat male infertility. In this regard, current emphasis is on the study of a role of endogenous antimicrobial peptides (AMPs) and their physiological activity during the maturation and functioning of male germ cells. AMPs are unique components of the innate immune system. They not only provide protection against bacteria, viruses, and fungi, but also have relatively diverse biological effects. These effects are closely related to the ability of AMPs to be directly involved in the physiological processes of post-testicular maturation of germ cells, in modification of the plasma membranes of sperms in the epididymis, and their capacitation in the female reproductive tract. This review focuses on the current understanding of the role of epididymal AMPs with regard to the functioning of sperm in normal and pathological conditions.

On the role of germ cells in planarian regeneration

Development ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 53-63
Author(s):  
V. Gremigni ◽  
C. Miceli ◽  
I. Puccinelli
Keyword(s):  
Chromosome Number ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Karyological Analysis ◽  
Blastema Formation ◽  
Planarian Regeneration ◽  
Somatic Tissues ◽  
Caudal Area ◽  
Complete Regeneration

Specimens from a polyploid biotype of Dugesia lugubris s.l. were used to clarify the role and fate of germ cells during planarian regeneration. These specimens provide a useful karyological marker because embryonic and somatic cells (3n = 12) can be easily distinguished from male (2n = 8) and female (6n = 24) germ cells by their chromosome number. We succeed in demonstrating how primordial germ cells participate in blastema formation and take part in rebuilding somatic tissues. This evidence was obtained by cutting each planarian specimen twice at appropriate levels. The first aimed to induce primordial germ cells to migrate to the wound. The second cut was performed after complete regeneration and aimed to obtain a blastema from a cephalic or caudal area devoid of gonads. A karyological analysis of mitotic cells present in each blastema obtained after the second cut provided evidence that cells, originally belonging to the germ lines, are still present in somatic tissues even months after complete regeneration. The role of primordial germ cells in planarian regeneration was finally discussed in relation to the phenomenon of metaplasia or transdifferentiation.

Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Development ◽  
2022 ◽  
Author(s):  
Yuki Naitou ◽  
Go Nagamatsu ◽  
Nobuhiko Hamazaki ◽  
Kenjiro Shirane ◽  
Masafumi Hayashi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Splice Variant ◽  
Epithelial To Mesenchymal Transition ◽  
Functional Relationship ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Cell Lineage ◽  
Animal Kingdom ◽  
Mesenchymal Transition

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

scholarly journals The Mammalian Ovary from Genesis to Revelation

2009 ◽  
Vol 30 (6) ◽  
pp. 624-712 ◽  
Author(s):  
Mark A. Edson ◽  
Ankur K. Nagaraja ◽  
Martin M. Matzuk
Keyword(s):  
Germ Cells ◽  
Ovarian Function ◽  
Primordial Germ Cells ◽  
Bioactive Molecules ◽  
Sex Characteristics ◽  
Germline Development ◽  
Peptide Growth Factors ◽  
Development And Differentiation ◽  
Common Destiny ◽  
Female Germline

Abstract Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago.

PIWIs maintain testis apoptosis to remove abnormal germ cells in Eriocheir sinensis

Reproduction ◽  
2021 ◽  
Author(s):  
Bang-Hong Wei ◽  
Jia-Hao Ni ◽  
Tong Yang ◽  
Shuang-Li Hao ◽  
Wan-Xi Yang
Keyword(s):  
B Cell ◽  
Germ Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Eriocheir Sinensis ◽  
Germline Development ◽  
P53 Pathway ◽  
Apoptosis Pathway ◽  
Encoded Proteins

PIWI proteins play important roles in germline development in the mammals. However, the functions of PIWIs in crustaceans remain unknown. In the present study, we identified three Piwis from the testis of Eriocheir sinensis (E. sinensis). Three Piwi genes encoded proteins with typical features of PIWI subfamilies and were highly expressed in the testis. Three PIWIs could be detected in the cytoplasm of spermatocytes and spermatids, while in spermatozoa, we could only detect PIWI1 and PIWI3 in the nucleus. The knockdown of PIWIs by dsRNA significantly affected the formation of the nuclei in spermatozoa, which resulted in deviant and irregular nuclei. PIWI defects significantly inhibited the apoptosis of abnormal germ cells through the caspase-dependent apoptosis pathway and p53 pathway. Knockdown of PIWIs inhibited the expression of caspase3, 7, 8, and p53 without affecting Bcl2 (B-cell lymphoma gene 2), Bax (B-cell lymphoma-2-associated X) and BaxI (B-cell lymphoma-2-associated X inhibitor), which further significantly increased abnormal spermatozoa in the knockdown-group crabs. These results show a new role of PIWI proteins in crustaceans that is different from that in mammals. In summary, PIWIs play roles in the formation of the germline nucleus and can maintain apoptosis in abnormal germ cells to remove abnormal germ cells in E. sinensis.

Functional requirement of gp130-mediated signaling for growth and survival of mouse primordial germ cells in vitro and derivation of embryonic germ (EG) cells

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1235-1242 ◽  
Author(s):  
U. Koshimizu ◽  
T. Taga ◽  
M. Watanabe ◽  
M. Saito ◽  
Y. Shirayoshi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Intracellular Signaling ◽  
Primordial Germ Cells ◽  
Cell Formation ◽  
Embryonic Stem ◽  
Oncostatin M ◽  
Receptor Complexes ◽  
Binding Subunit

Leukemia inhibitory factor (LIF) is a cytokine known to influence proliferation and/or survival of mouse primordial germ cells (PGC) in culture. The receptor complex for LIF comprises LIF-binding subunit and non-binding signal transducer, gp130. The gp130 was originally identified as a signal-transducing subunit of interleukin (IL)-6 and later also found to be a functional component of receptor complexes for other LIF-related cytokines (oncostatin M [OSM], ciliary neurotrophic factor [CNTF] and IL-11). In this study, we have analyzed the functional role of gp130-mediated signaling in PGC growth in vitro. OSM was able to fully substitute for LIF; both cytokines promoted the proliferation of migratory PGC (mPGC) and enhanced the viability of postmigratory (colonizing) PGC (cPGC) when cultured on SI/SI4-m220 cells. Interestingly, IL-11 stimulated mPGC growth comparable to LIF and OSM, but did not affect cPGC survival. IL-6 and CNTF did not affect PGC. In addition, a combination of IL-6 and soluble IL-6 binding subunit (sIL-6R), which is known to activate intracellular signaling via gp130, fully reproduced the LIF action of PGC. Both in the presence and absence of LIF, addition of neutralizing antibody against gp130 in culture remarkably blocked cPGC survival. These results suggest a pivotal role of gp130 in PGC development, especially that it is indispensable for cPGC survival as comparable to the c-KIT-mediated action. We have further demonstrated that a combination of LIF with forskolin or retinoic acid, a potent mitogen for PGC, supported the proliferation of PGC, leading to propagation of the embryonic stem cell-like cells, termed embryonic germ (EG) cells. Since EG cells were also obtained by using OSM or the IL-6/sIL-6R complex in place of LIF, a significant contribution of gp130-mediated signaling in EG cell formation was further suggested.

scholarly journals Vitamin D Status Impacts Genital Mucosal Immunity and Markers of HIV-1 Susceptibility in Women

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3176
Author(s):  
Sharon M. Anderson ◽  
Andrea R. Thurman ◽  
Neelima Chandra ◽  
Suzanne S. Jackson ◽  
Susana Asin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Reproductive Tract ◽  
Serum Vitamin ◽  
Female Reproductive Tract ◽  
High Dose ◽  
Vitamin D Status ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Hiv 1

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

scholarly journals N-Cadherin Is Critical for the Survival of Germ Cells, the Formation of Steroidogenic Cells, and the Architecture of Developing Mouse Gonads

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1610 ◽  
Author(s):  
Rafal P. Piprek ◽  
Michal Kolasa ◽  
Dagmara Podkowa ◽  
Malgorzata Kloc ◽  
Jacek Z. Kubiak
Keyword(s):  
Germ Cells ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Somatic Cells ◽  
Gonad Development ◽  
Knock Out ◽  
Gonad Differentiation ◽  
Steroidogenic Cells ◽  
The Individual ◽  
And Function

Normal gonad development assures the fertility of the individual. The properly functioning gonads must contain a sufficient number of the viable germ cells, possess a correct architecture and tissue structure, and assure the proper hormonal regulation. This is achieved by the interplay between the germ cells and different types of somatic cells. N-cadherin coded by the Cdh2 gene plays a critical role in this interplay. To gain an insight into the role of N-cadherin in the development of mouse gonads, we used the Cre-loxP system to knock out N-cadherin separately in two cell lines: the SF1+ somatic cells and the OCT4+ germ cells. We observed that N-cadherin plays a key role in the survival of both female and male germ cells. However, the N-cadherin is not necessary for the differentiation of the Sertoli cells or the initiation of the formation of testis cords or ovigerous cords. In the later stages of gonad development, N-cadherin is important for the maintenance of testis cord structure and is required for the formation of steroidogenic cells. In the ovaries, N-cadherin is necessary for the formation of the ovarian follicles. These results indicate that N-cadherin plays a major role in gonad differentiation, structuralization, and function.

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