scholarly journals Functional similarity between TGF-beta type 2 and type 1 receptors in the female reproductive tract

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nan Ni ◽  
Xin Fang ◽  
Qinglei Li
Keyword(s):  
Reproductive Tract ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Female Reproductive Tract ◽  
Functional Similarity ◽  
Conditional Knockout ◽  
Receptor Type ◽  
Tgfβ Signaling ◽  
Conditional Deletion

AbstractTransforming growth factor β (TGFβ) signaling plays critical roles in reproductive development and function. TGFβ ligands signal through the TGFβ receptor type 2 (TGFBR2)/TGFBR1 complex. As TGFBR2 and TGFBR1 form a signaling complex upon ligand stimulation, they are expected to be equally important for propagating TGFβ signaling that elicits cellular responses. However, several genetic studies challenge this concept and indicate that disruption of TGFBR2 or TGFBR1 may lead to contrasting phenotypic outcomes. We have shown that conditional deletion of Tgfbr1 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre causes oviductal and myometrial defects. To determine the functional requirement of TGFBR2 in the female reproductive tract and the potential phenotypic divergence/similarity resulting from conditional ablation of either receptor, we generated mice harboring Tgfbr2 deletion using the same Cre driver that was previously employed to target Tgfbr1. Herein, we found that conditional deletion of Tgfbr2 led to a similar phenotype to that of Tgfbr1 deletion in the female reproductive tract. Furthermore, genetic removal of Tgfbr1 in the Tgfbr2-deleted uterus had minimal impact on the phenotype of Tgfbr2 conditional knockout mice. In summary, our results reveal the functional similarity between TGFBR2 and TGFBR1 in maintaining the structural integrity of the female reproductive tract.

scholarly journals Transforming growth factor beta signaling and decidual integrity in mice†

2020 ◽  
Vol 103 (6) ◽  
pp. 1186-1198
Author(s):  
Xin Fang ◽  
Nan Ni ◽  
Yang Gao ◽  
John P Lydon ◽  
Ivan Ivanov ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Female Reproductive Tract ◽  
Molecular Properties ◽  
Conditional Knockout ◽  
Decidual Cell ◽  
Tgfβ Signaling ◽  
Growth Factor Beta

Abstract Transforming growth factor beta (TGFβ) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFβ (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFβ signaling in decidual development and function remains poorly defined. Our objective is to determine the impact of uterine-specific deletion of Tgfbr1 on decidual integrity, with a focus on the cellular and molecular properties of the decidua during development. Our results show that the developmental dynamics of the decidua is altered in TGFBR1 conditionally depleted uteri from embryonic day (E) 5.5 to E8.5, substantiated by downregulation of genes associated with inflammatory responses and uterine natural killer cell abundance, reduced presence of nondecidualized fibroblasts in the antimesometrial region, and altered decidual cell development. Notably, conditional ablation of TGFBR1 results in the formation of decidua containing more abundant alpha smooth muscle actin (ACTA2)-positive cells at the peripheral region of the antimesometrial side versus controls at E6.5–E8.5. This finding is corroborated by upregulation of a subset of smooth muscle marker genes in Tgfbr1 conditionally deleted decidua at E6.5 and E8.5. Moreover, increased cell proliferation and enhanced decidual ERK1/2 signaling were found in Tgfbr1 conditional knockout mice upon decidual regression. In summary, conditional ablation of TGFBR1 in the uterus profoundly impacts the cellular and molecular properties of the decidua. Our results suggest that TGFBR1 in uterine epithelial and stromal compartments is important for the integrity of the decidua, a transient but crucial structure that supports embryo development.

scholarly journals Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility

2008 ◽  
Vol 22 (10) ◽  
pp. 2336-2352 ◽  
Author(s):  
Ankur K. Nagaraja ◽  
Claudia Andreu-Vieyra ◽  
Heather L. Franco ◽  
Lang Ma ◽  
Ruihong Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Reproductive Tract ◽  
Somatic Cells ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Conditional Knockout ◽  
Female Sterility ◽  
Small Interfering Rnas ◽  
Conditional Deletion ◽  
And Function

Abstract Dicer is an evolutionarily conserved ribonuclease III that is necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown that Dicer plays important roles in the mammalian germline and early embryogenesis, the functions of Dicer-dependent pathways in the somatic cells of the female reproductive tract are unknown. Using a transgenic line in which Cre recombinase is driven by the anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1 in the mesenchyme of the developing Müllerian ducts and postnatally in ovarian granulosa cells and mesenchyme-derived cells of the oviducts and uterus. Deletion of Dicer in these cell types results in female sterility and multiple reproductive defects including decreased ovulation rates, compromised oocyte and embryo integrity, prominent bilateral paratubal (oviductal) cysts, and shorter uterine horns. The paratubal cysts act as a reservoir for spermatozoa and oocytes and prevent embryos from transiting the oviductal isthmus and passing the uterotubal junction to enter the uterus for implantation. Deep sequencing of small RNAs in oviduct revealed down-regulation of specific miRNAs in Dicer conditional knockout females compared with wild type. The majority of these differentially expressed miRNAs are predicted to regulate genes important for Müllerian duct differentiation and mesenchyme-derived structures, and several of these putative target genes were significantly up-regulated upon conditional deletion of Dicer1. Thus, our findings reveal diverse and critical roles for Dicer and its miRNA products in the development and function of the female reproductive tract.

scholarly journals Transforming Growth Factor β Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function

PLoS Genetics ◽  
2011 ◽  
Vol 7 (10) ◽  
pp. e1002320 ◽  
Author(s):  
Qinglei Li ◽  
Julio E. Agno ◽  
Mark A. Edson ◽  
Ankur K. Nagaraja ◽  
Takashi Nagashima ◽  
...  
Keyword(s):  
Growth Factor ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Female Reproductive Tract ◽  
Receptor Type ◽  
Β Receptor ◽  
And Function

Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract

2014 ◽  
Vol 307 (3) ◽  
pp. E345-E354 ◽  
Author(s):  
Jose Barrera ◽  
Ken L. Chambliss ◽  
Mohamed Ahmed ◽  
Keiji Tanigaki ◽  
Bonne Thompson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Composition ◽  
Hepatic Steatosis ◽  
Glucose Homeostasis ◽  
Reproductive Tract ◽  
Body Weight Gain ◽  
Female Reproductive Tract ◽  
Minimal Impact ◽  
Conjugated Estrogen

Despite the capacity of estrogens to favorably regulate body composition and glucose homeostasis, their use to combat obesity and type 2 diabetes is not feasible, because they promote sex steroid-responsive cancers. The novel selective estrogen receptor modulator (SERM) bazedoxifene acetate (BZA) uniquely antagonizes both breast cancer development and estrogen-related changes in the female reproductive tract. How BZA administered with conjugated estrogen (CE) or alone impacts metabolism is unknown. The effects of BZA or CE + BZA on body composition and glucose homeostasis were determined in ovariectomized female mice fed a Western diet for 10–12 wk. In contrast to vehicle, estradiol (E2), CE, BZA, and CE + BZA equally prevented body weight gain by 50%. In parallel, all treatments caused equal attenuation of the increase in body fat mass invoked by the diet as well as the increases in subcutaneous and visceral white adipose tissue. Diet-induced hepatic steatosis was attenuated by E2 or CE, and BZA alone or with CE provided even greater steatosis prevention; all interventions improved pyruvate tolerance tests. Glucose tolerance tests and HOMA-IR were improved by E2, CE, and CE + BZA. Whereas E2 or CE alone invoked a uterotrophic response, BZA alone or CE + BZA had negligible impact on the uterus. Thus, CE + BZA affords protection from diet-induced adiposity, hepatic steatosis, and insulin resistance with minimal impact on the female reproductive tract in mice. These combined agents may provide a valuable new means to favorably regulate body composition and glucose homeostasis and combat fatty liver.

Angiotensin II induces apoptosis in rat glomerular epithelial cells

2002 ◽  
Vol 283 (1) ◽  
pp. F173-F180 ◽  
Author(s):  
Guohua Ding ◽  
Krishna Reddy ◽  
Aditi A. Kapasi ◽  
Nicholas Franki ◽  
Nora Gibbons ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Time Dependent ◽  
Receptor Type ◽  
Dependent Manner ◽  
Ang Ii ◽  
Glomerular Epithelial Cells ◽  
Induced Apoptosis ◽  
Tgf Β1

ANG II has been shown to modulate kidney cell growth and contribute to the pathobiology of glomerulosclerosis. Glomerular visceral epithelial cell (GEC) injury or loss is considered to play a pivotal role in the initiation and progression of glomerulosclerosis. In the present study, we investigated the effect of ANG II on GEC apoptosis. Rat GECs were incubated with increasing doses of ANG II for variable time periods. Apoptosis was evaluated by cell nucleus staining and DNA fragmentation assay. ANG II induced GEC apoptosis in a dose- and time-dependent manner. The proapoptotic effect was attenuated by the ANG II receptor type 1 antagonist losartan or the ANG II receptor type 2 antagonist PD-123319 and was completely blocked by incubation with the combined antagonists. Moreover, ANG II stimulated transforming growth factor (TGF)-β1 production as measured by ELISA. GECs exposed to TGF-β1 demonstrated a dose- and time-dependent increase in apoptosis. ANG II-induced apoptosis was significantly inhibited by addition of anti-TGF-β1 antibody. ANG II also upregulated the expression of Fas, FasL, and Bax and downregulated the expression of Bcl-2 in GECs. These studies suggest that ANG II induces GEC apoptosis by a mechanism involving TGF-β1 expression that may, importantly, contribute to the pathogenesis of glomerulosclerosis.

Transforming growth factor-? (TGF?) in porcine seminal plasma

2011 ◽  
Vol 23 (6) ◽  
pp. 748 ◽  
Author(s):  
Sean O'Leary ◽  
David T. Armstrong ◽  
Sarah A. Robertson
Keyword(s):  
Growth Factor ◽  
Seminal Plasma ◽  
Reproductive Tract ◽  
Transforming Growth Factor ◽  
Seminal Fluid ◽  
Transforming Growth Factor Β ◽  
Interferon Γ ◽  
Female Reproductive Tract ◽  
Active Constituent ◽  
Sperm Density

Bioactive factors in seminal plasma induce cellular and molecular changes in the female reproductive tract after coitus. An active constituent of seminal plasma in mice and humans is the potent immune-modulating cytokine transforming growth factor-β (TGFβ). To investigate whether TGFβ is present in boar seminal plasma, TGFβ1 and TGFβ2 were measured by immunoassay. High levels of TGFβ1 and TGFβ2 were detected in 100% of seminal fluid samples from 73 boars. Both were predominantly in the active, not latent form. Interferon-γ (IFNγ) and lipopolysaccharide (LPS), agents that interact with TGFβ signalling, were detectable in 5% and 100% of samples, respectively. TGFβ1 and TGFβ2 concentrations varied widely between boars, but correlated with each other and with sperm density, and remained relatively constant within individual boars over a 6-month period. Frequent semen collection substantially diminished the concentration of both TGFβ isoforms. Using retrospective breeding data for 44 boars, no correlation between TGFβ content and boar reproductive performance by artificial insemination (AI) with diluted semen was found. It is concluded that TGFβ is abundant in boar seminal plasma, leading to the speculation that, in pigs, TGFβ may be a male–female signalling agent involved in immune changes in the female reproductive tract elicited by seminal fluid.

scholarly journals Primary Amenorrhea Due to Anatomical Abnormalities of the Reproductive Tract: Molecular Insight

2021 ◽  
Vol 22 (21) ◽  
pp. 11495
Author(s):  
Karina Kapczuk ◽  
Witold Kędzia
Keyword(s):  
Reproductive Tract ◽  
Androgen Insensitivity Syndrome ◽  
Female Reproductive Tract ◽  
Unknown Primary ◽  
Primary Amenorrhea ◽  
Complete Androgen Insensitivity Syndrome ◽  
Associated Malformations ◽  
Type 3

Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS), and cervical and vaginal anomalies that completely obstruct the reproductive tract. Karyotype abnormalities do not exclude the diagnosis of MRKHS. Familial cases of Müllerian anomalies and associated malformations of the urinary and skeletal systems strongly suggest a complex genetic etiology, but so far, the molecular mechanism in the vast majority of cases remains unknown. Primary amenorrhea may also be the first presentation of complete androgen insensitivity syndrome, steroid 5α-reductase type 2 deficiency, 17β-hydroxysteroid dehydrogenase type 3 deficiency, and Leydig cells hypoplasia type 1; therefore, these disorders should be considered in the differential diagnosis of the congenital absence of the uterus and vagina. The molecular diagnosis in the majority of these cases can be established.

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