Function and therapeutic potential of G protein‐coupled receptors in epididymis

Zhang, Dao Lai; Wang, Yanfei; Lin, Hui Ju; Sun, Yujing; Wang, Mingwei; Jia, Yingli; Yu, Xiao; Jiang, Hui; Xu, Wei; Sun, Junying; Xu, Zhigang

doi:10.1111/bph.15252

Cited by 17 publications

(10 citation statements)

References 203 publications

(430 reference statements)

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“…As the incidence of infertility has increased continuously in recent years, an increasing number of couples are turning to assisted reproductive technology for fertility treatment [ 1 , 2 ]. The goal of assisted reproductive technology is to select embryos with maximum potential for transfer and obtain a single healthy live pregnancy in the shortest time.…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles

Liu

Shen

Yang

et al. 2022

International Journal of Endocrinology

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Research Question. What is the incidence of de novo chromosome abnormalities (>4 Mb), and are they related to embryo parameters in preimplantation genetic testing for chromosome structural rearrangement (PGT-SR) cycles and preimplantation genetic testing for aneuploidy (PGT-A) cycles? Design. In total, 456 PGT cycles, including 283 PGT-SR cycles and 173 PGT-A cycles, were assessed through comprehensive chromosome screening (CCS) from January 2017 to June 2020 at the Department of Reproductive Medicine of the Third Affiliated Hospital of Zhengzhou University. Trophectoderm (TE) biopsies were sequenced using next-generation sequencing (NGS). The incidence of de novo chromosome abnormalities was calculated, and the relationships between de novo chromosome abnormality rates and maternal age, number of oocytes retrieved, and parameters of cleavage-stage embryos and blastocyst-stage embryos were investigated. Results. The incidence of de novo chromosome abnormalities was 28.0% (318/1,135) in the PGT-SR cycles and 36.3% (214/590) in the PGT-A cycles, which increased with maternal age in both PGT-SR cycles ( P = 0.018) and PGT-A cycles ( P < 0.001). The incidence of de novo chromosome abnormalities was related to TE grade ( P < 0.001), internal cell mass grade ( P = 0.002), and development speed (day 5 vs. day 7: P < 0.001) of blastocyst-stage embryos. The incidence of de novo chromosomal abnormalities was irrelevant to the number of oocytes retrieved and the parameters of the embryo at the cleavage stage. Conclusion. Blastocysts with higher morphology scores and faster progression had a lower incidence of de novo chromosome abnormalities, especially complex chromosome abnormalities. De novo chromosome abnormalities may negatively affect the morphological grading of blastocysts. Our findings will provide valuable information to the fertility doctor for embryo selection in non-PGT cycles.

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Section: Introductionmentioning

confidence: 99%

The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles

Liu

Shen

Yang

et al. 2022

International Journal of Endocrinology

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“…On the other hand, the increase of PEG2 caused by carbon monoxide in macrophages may activate downstream PKG to downregulate IL-1b (Lin et al, 2010). The latest research indicates that cGMP has the potential to treat infertility in the epididymis (Zhang et al, 2020). In this experiment, CNP could increase level of cGMP in RAW264.7 macrophages, and its effect on NF-kB signal pathway was inhibited by PKG inhibitor KT5823.…”

Section: Discussionmentioning

confidence: 77%

C-Type Natriuretic Peptide Plays an Anti-Inflammatory Role in Rat Epididymitis Induced by UPEC

Mei

Zhang

et al. 2021

Front. Cell. Infect. Microbiol.

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Human epididymitis is mainly caused by retrograde urinary tract infection with uropathogenic Escherichia coli (UPEC). This disease is an important factor (accounting for 20–30%) causing male infertility. C-type natriuretic peptide (CNP), a protein composed of 22 amino acids, is proved to play an immunoregulatory role in respiratory and cardiovascular systems. CNP is expressed extremely high in the epididymis, but whether CNP plays the same role in acute epididymitis is unclear. At first, we established an acute caput epididymitis model in rats with UPEC and treated them with CNP to measure inflammatory damage. Then RNA-seq transcriptome technology was used to reveal potential signal pathways. Secondly, the turbidity and activity of UPEC were assessed using a microplate reader and the amount of UPEC by agar plates after incubation with CNP. Thirdly, macrophages in caput epididymis were tested by immunohistochemistry (IHC). Meanwhile, lipopolysaccharide (LPS) with or without CNP was used to stimulate the macrophage (RAW264.7) in vitro and to detect the expression level of pro-inflammatory factors. Finally, the macrophage (RAW264.7) was treated with CNP, 8-Br-cGMP [cyclic guanosinc monophosphate (cGMP) analog] and KT5823 [protein kinase G (PKG) inhibitor], and the expression level of nuclear factor-k-gene binding (NF-kB) signal pathway was examined. The results showed that the damage of epididymis induced by UPEC as well as the pro-inflammatory factors could be alleviated significantly with CNP treatment. CNP could inhibit the activity and numbers of bacteria in both in vivo and in vitro experiments. Moreover, CNP repressed the invasion, and the expression of pro-inflammatory factors (such as NF-kB, IL-1β, IL-6, TNF-α) in macrophages and its effect could be inhibited by KT5823. Therefore, we drew a conclusion from the above experiments that CNP alleviates the acute epididymitis injury induced by UPEC. On one hand, CNP could inhibit the growth of UPEC. On the other hand, CNP could decrease invasion and inflammatory reaction of macrophages; the mechanism was involved in inhibiting NF-kB signal pathway through the cGMP/PKG in macrophages. This research would open up the possibility of using CNP as a potential treatment for epididymitis.

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“…GPCRs are the largest family of surface receptors widely expressed in the body and play a vital role in multiple biological processes [ 43 , 44 , 45 , 46 , 47 ]. ADRβ 3 is one of the members of this family and is highly expressed in adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of the Obesity-Linked Variant of the β3-Adrenergic Receptor

Haji

Mahri

Aloraij

et al. 2021

IJMS

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Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 is associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike adrenergic receptor β2 (ADRβ2), agonist-induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties, and there was no significant impact of the substitution of tryptophan with arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

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Function and therapeutic potential of G protein‐coupled receptors in epididymis

Cited by 17 publications

References 203 publications

The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles

The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles

C-Type Natriuretic Peptide Plays an Anti-Inflammatory Role in Rat Epididymitis Induced by UPEC

Functional Characterization of the Obesity-Linked Variant of the β3-Adrenergic Receptor

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