scholarly journals Molecular mechanisms of development of the human fetal female reproductive tract

2017 ◽  
Vol 97 ◽  
pp. 54-72 ◽  
Author(s):  
Gerald R. Cunha ◽  
Takeshi Kurita ◽  
Mei Cao ◽  
Joel Shen ◽  
Stanley Robboy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Mechanisms Of Development

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 Prostasomes: extracellular vesicles from the prostate

Reproduction ◽  
2014 ◽  
Vol 147 (1) ◽  
pp. R1-R14 ◽  
Author(s):  
Marian Aalberts ◽  
Tom A E Stout ◽  
Willem Stoorvogel
Keyword(s):  
Prostate Cancer ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Single Type ◽  
Prostatic Fluid ◽  
Prostate Epithelial Cells ◽  
Cancer Spread ◽  
Peripheral Blood Plasma

The term ‘prostasomes’ is generally used to classify the extracellular vesicles (EVs) released into prostatic fluid by prostate epithelial cells. However, other epithelia within the male reproductive tract also release EVs that mix with ‘true’ prostasomes during semen emission or ejaculation. Prostasomes have been proposed to regulate the timing of sperm cell capacitation and induction of the acrosome reaction, as well as to stimulate sperm motility where all three are prerequisite processes for spermatozoa to attain fertilising capacity. Other proposed functions of prostasomes include interfering with the destruction of spermatozoa by immune cells within the female reproductive tract. On the other hand, it is unclear whether the distinct presumed functions are performed collectively by a single type of prostasome or by separate distinct sub-populations of EVs. Moreover, the exact molecular mechanisms through which prostasomes exert their functions have not been fully resolved. Besides their physiological functions, prostasomes produced by prostate tumour cells have been suggested to support prostate cancer spread development, and prostasomes in peripheral blood plasma may prove to be valuable biomarkers for prostate cancer.

scholarly journals Major Critical Periods in Developmental Pathogenomics of Endometriosis

2019 ◽  
Vol 3 (1) ◽  
pp. 01-02
Author(s):  
Vladislav Baranov
Keyword(s):  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Benign Tumor ◽  
Reproductive Organs ◽  
Genetic Program ◽  
Female Reproductive Tract ◽  
Critical Periods ◽  
Uterine Endometrium ◽  
Common Benign Tumor ◽  
Major Genome

In spite on numerous experimental and clinical data molecular mechanisms of endometriosis (EM) - the most common benign tumor of the female reproductive tract still remains obscure . The deciphering enigmas of EM gave a birth to a number of hypothesis . System genetics approach used in our studies of common diseases support the existence of special genetic program of EM operative in its development. It is taken for granted that EM results from abnormal differentiation of stem cells (SC). Two major sources of EM SC are considered : SC disseminated throughout peritoneum during female reproductive organs embryogenesis , SC from junction zone the uterine endometrium (2) [6]. According to our reviewed hypothesis [7] the genetic program of EM consists of several critical periods (CP) [8] corresponding to three crucial events in EM development with each of them corresponding to major genome reprogramming in EM cells.

scholarly journals Structure and Function of Caltrin (Calcium Transport Inhibitor) Proteins

2017 ◽  
Vol 10 ◽  
pp. 117862641774582
Author(s):  
Ernesto Javier Grasso ◽  
Carlos Enrique Coronel
Keyword(s):  
Intracellular Signaling ◽  
Calcium Transport ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Structural Features ◽  
Female Reproductive Tract ◽  
Sperm Cells ◽  
Transport Inhibitor ◽  
Acrosomal Exocytosis ◽  
And Function

Caltrin (calcium transport inhibitor) is a family of small and basic proteins of the mammalian seminal plasma which bind to sperm cells during ejaculation and inhibit the extracellular Ca2+ uptake, preventing the premature acrosomal exocytosis and hyperactivation when sperm cells ascend through the female reproductive tract. The binding of caltrin proteins to specific areas of the sperm surface suggests the existence of caltrin receptors, or precise protein-phospholipid arrangements in the sperm membrane, distributed in the regions where Ca2+ influx may take place. However, the molecular mechanisms of recognition and interaction between caltrin and spermatozoa have not been elucidated. Therefore, the aim of this article is to describe in depth the known structural features and functional properties of caltrin proteins, to find out how they may possibly interact with the sperm membranes to control the intracellular signaling that trigger physiological events required for fertilization.

scholarly journals Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression

2020 ◽  
Vol 12 (7) ◽  
pp. 515-529 ◽  
Author(s):  
Yue Liu ◽  
Chujun Zhang ◽  
Shiyao Wang ◽  
Yanqin Hu ◽  
Jia Jing ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Critical Role ◽  
Dynamic Control ◽  
Female Reproductive Tract ◽  
Sperm Maturation ◽  
Regulatory Subunit ◽  
Membrane Remodeling ◽  
Membrane Diffusion

Abstract After leaving the testis, mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract. These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling, which is requisite for sperm to acquire forward motility and induce fertilization. However, the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood. Herein, we show that PPP3R2, a testis-specific regulatory subunit of protein phosphatase 3 (an isoform of calcineurin in the testis), is essential for sperm maturation and capacitation. Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects. One very noteworthy change includes increases in sperm membrane stiffness. Moreover, PPP3R2 regulates sperm maturation and capacitation via (i) modulation of membrane diffusion barrier function at the annulus and (ii) facilitation of cholesterol efflux during sperm capacitation. Taken together, PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation.

scholarly journals The Krüppel-like factors in female reproductive system pathologies

2015 ◽  
Vol 54 (2) ◽  
pp. R89-R101 ◽  
Author(s):  
Rosalia C M Simmen ◽  
Melissa E Heard ◽  
Angela M Simmen ◽  
Maria Theresa M Montales ◽  
Meera Marji ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Steroid Hormone ◽  
Female Reproductive Tract ◽  
Nuclear Proteins ◽  
Female Reproductive System ◽  
Binding Partners ◽  
Regulatory Circuits ◽  
Estrogen And Progesterone Receptor

Female reproductive tract pathologies arise largely from dysregulation of estrogen and progesterone receptor signaling, leading to aberrant cell proliferation, survival, and differentiation. The signaling pathways orchestrated by these nuclear receptors are complex, require the participation of many nuclear proteins serving as key binding partners or targets, and involve a range of paracrine and autocrine regulatory circuits. The members of the Krüppel-like factor (KLF) family of transcription factors are ubiquitously expressed in reproductive tissues and have been increasingly implicated as critical co-regulators and integrators of steroid hormone actions. Herein, we explore the involvement of KLF family members in uterine pathology, describe their currently known molecular mechanisms, and discuss their potential as targets for therapeutic intervention.

scholarly journals Swine sperm induces neutrophil extracellular traps that entangle sperm and embryos

Reproduction ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 217-225
Author(s):  
Zhengkai Wei ◽  
Tingting Yu ◽  
Jingjing Wang ◽  
Chaoqun Wang ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Sperm Motility ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Embryo Implantation ◽  
Neutrophil Extracellular Traps ◽  
Mapk Signaling ◽  
Female Reproductive Tract ◽  
Extracellular Traps

Sperm motility, fertilization and embryo implantation are several important factors in reproduction. Except healthy state of sperm and embryo themselves, successful pregnancy is closely related to the status of female reproductive tract immune system. Increased immune cells in reproductive tract often leads to low sperm motility and low chance of embryo implantation, but the mechanisms remain not well clarified. The aim of this study is to investigate the direct effects of swine polymorphonuclear neutrophils (PMNs) on sperm or embryo in vitro and then try to clarify the molecular mechanisms undergoing the phenomenon. Swine sperm-triggered neutrophil extracellular traps (NETs) were observed by scanning electron microscopy (SEM). PMNs phagocytosis of sperms was examined by transmission electron microscopy (TEM). Sperm-triggered NETs were quantitated by Pico Green®. Vital staining of the interaction between PMNs and embryo were observed by using confocal microscope. It was showed that PMNs were directly activated by sperm in the form of phagocytosis or casting NETs and that sperm-triggered-NETs formation was made up with DNA co-located with citrullinated histone 3 (citH3) and myeloperoxidase (MPO). In addition, the potential mechanism of NETs release was relevant to NADPH oxidase, ERK1/2 or p38 MAPK signaling pathways. Of great interest was that swine embryo was first found entangled in NETs in vitro, but the function and mechanism of this action in vivo fertilization still needed further investigation. In conclusion, this is the first report about swine sperm-induced NETs that entangle sperm and embryo, which might provide an entirely understanding of swine reproductive physiology and immunology.

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