Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC)

Wu, Yihan; Zhang, Xiao; Fu, Yong; Liu, Jing; Xue, Yangfei; Li, Qun

doi:10.3390/ijms23073843

Cited by 8 publications

(8 citation statements)

References 31 publications

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“…The TgPGRMC gene motif contained a conserved hormone-binding site, six Casein Kinase II (CK2) phosphorylation sites, three Protein kinase C (PKC, EC 2.7. 11.13) phosphorylation sites, and four myristyl sites [30] . T. gondii alters the expression of hormonal receptors, by decreasing prolactin receptor (PRLR), estrogen receptor beta (Erβ), and progesterone receptor (PR), which leads to increased circulating levels of PRL, estrogen, and progesterone [27] .…”

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

“…The infectivity and pathogenicity or virulence potential of T.gondii in humans could be influenced by the host's progesterone levels [27,30] . This was demonstrated in a recent in vitro study by Wu et al (2022), where T. gondii treated with progesterone resulted in the inhibition of the invasion and proliferation level of otherwise, a rapidly growing life stage of T. gondii [27,30] . When cultured for 48 h with different concentrations of progesterone in vitro, T. gondii's daughter cells exhibited altered morphology (cytoskeleton) and budding patterns (an abnormal division of the apicoplast) and enhanced autophagy in a concentration-dependent manner [30] .…”

Section: Resultsmentioning

confidence: 99%

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The Relationship Between Toxoplasmosis and Concentration of Prolactin and Progesterone in Pregnant Women

Alshammary,

Alanazi,

Alghamdi

et al. 2024

ijirms

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Toxoplasma gondii (T.gondii) is an intracellular protozoon that causes toxoplasmosis in one-third of the world's population. During pregnancy, the prevalence of toxoplasmosis rises during the second and third trimesters causing abortion and a mild mononucleosis-like syndrome. Normally, progesterone rises during pregnancy, but in the case of toxoplasmosis, the body raises prolactin to inhibit T. gondii. The present study investigated the relationship between Toxoplasma gondii infection (toxoplasmosis) and the concentration of both prolactin and progesterone in infected pregnant women. A systematic review approach was conducted to research the aim of this study. PubMed, Scopus, Web of Science, and Google Scholar were searched using the following keywords “Toxoplasma gondii” or “T.gondii” AND “protozoon” OR “toxoplasmosis” OR “animals” OR “prolactin” OR “progesterone.” Only primary studies were included, whereas reviews and non-experimental studies were excluded. Six studies met the inclusion criteria and were, therefore, reviewed in the present study. The six studies showed a reverse relationship between prolactin and progesterone, such that if one increases the other drops. Furthermore, Toxoplasmosis increased progesterone levels, which results in the suppression of prolactin levels. Thus, toxoplasmosis-induced progesterone secretion has an antagonistic effect on prolactin levels. Since prolactin strongly elicits innate and adaptive immune responses, toxoplasmosis-induced progesterone release dampens the immune response of the host and enhances susceptibility to severe toxoplasmosis.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Relationship Between Toxoplasmosis and Concentration of Prolactin and Progesterone in Pregnant Women

Alshammary,

Alanazi,

Alghamdi

et al. 2024

ijirms

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show abstract

“…A review of eight studies in humans and 22 in animals and cell cultures tried to evaluate the relationship between hormones and infection caused by T. gondii but did not find comparable data [ 62 ]. It was recently shown that progesterone, a critical hormone that supports pregnancy, significantly inhibited the invasion and proliferation of tachyzoites and identified a T. gondii progesterone membrane receptor protein that proves to be an essential link between T. gondii and progesterone [ 63 ]. Still, further studies are required to determine the mechanism of hormone action in the T. gondii infectious process.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasmosis Screening during Pregnancy in a Romanian Infectious Diseases Tertiary Center: Results of a 15 Years Follow-Up Program

Briciu,

Ionică,

Flonta

et al. 2023

Microorganisms

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Maternal infection with Toxoplasma gondii during pregnancy may have serious consequences for the fetus. In Romania, screening for toxoplasmosis is included in the first antenatal visit. A retrospective study was performed on all toxoplasmosis antenatal screening patients between May 2008 and February 2023. Twenty-seven thousand one hundred sixty-nine (27,169) pregnant women presented for prenatal screening once (22,858) or several times: during the same pregnancy (209) or during multiple pregnancies (4102). Thirty-one thousand six hundred fifty-eight (31,658) tests for IgM and IgG antibodies were performed. Nine thousand eighty-three (9083) tests (28.69%), corresponding to 7911 women (29.12%), were positive for IgG antibodies. The seroprevalence increased with patients’ age, decreased in time intervals, and was more frequently associated with rural residence. At risk for acquiring the infection during the pregnancy were women with negative anti-Toxoplasma IgG antibodies (70.88%), but only 0.9% of them presented for rescreening during the same pregnancy. Acute Toxoplasma infection (ATI) was suspected in 44 patients (0.16%) due to IgG seroconversion and/or low or borderline IgG avidity. A questionnaire follow-up interview was performed, and no congenital toxoplasmosis was identified in children born from mothers with probable ATI. Our study demonstrates poor compliance with the screening program in the Romanian population.

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“…As to progesterone, which failed to promote the invasion of T. gondii , it inhibited the growth of parasites and their pathogenicity in mice because of the reduced secretion of TgMIC2 and reduced gliding ability. Meanwhile, parasites cultured with progesterone resulted in abnormal division and disordered formation of the inner membrane complex [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of different drugs and hormone treatment on Toxoplasma gondii glutathione S-transferase 2

Zhu

Xue

et al. 2022

Parasites Vectors

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Background Glutathione S-transferase (GST) in eukaryotic organisms has multiple functions such as detoxifying endogenous/exogenous harmful substances to protect cells from oxidative damage, participating in sterol synthesis and metabolism, and regulating signaling pathways. Our previous work identified an important GST protein in Toxoplasma that contributes to vesicle trafficking called TgGST2, the deletion of which significantly reduces the virulence of the parasite. Meanwhile, we considered that TgGST2 may also play a role in other pathways of parasite life activities. Methods The tertiary structures of TgGST2 as well as estradiol (E2) and progesterone (P4) were predicted by trRosetta and Autodock Vina software, the binding sites were analyzed by PyMol's GetBox Plugin, and the binding capacity was evaluated using Discovery Studio plots software. We examined the influence of E2 and P4 on TgGST2 via glutathione S-transferase enzyme activity and indirect immunofluorescence assay (IFA) and through the localization observation of TgGST2 to evaluate its response ability in different drugs. Results TgGST2 could bind to exogenous E2 and P4, and that enzymatic activity was inhibited by the hormones in a concentration-dependent manner. Upon P4 treatment, the localization of TgGST2 changed from Golgi and vesicles to hollow circles, leading to abnormal localization of the molecular transporter Sortilin (VPS10) and microneme proteins (M2AP and MIC2), which ultimately affect the parasite life activities, but E2 had no significant effect. Moreover, diverse types of drugs had divergent effects on TgGST2, among which treatment with antifungal agents (voriconazole and clarithromycin), anticarcinogens (KU-60019, WYE-132 and SH5-07) and coccidiostats (dinitolmide and diclazuril) made the localization of TgGST2 appear in different forms, including dots, circles and rod shaped. Conclusions Our study shows that TgGST2 plays a role in sterol treatment and can be affected by P4, which leads to deficient parasite motility. TgGST2 exerts divergent effects in response to the different properties of the drugs themselves. Its responsiveness to diverse drugs implies a viable target for the development of drugs directed against Toxoplasma and related pathogenic parasites. Graphical Abstract

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Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC)

Cited by 8 publications

References 31 publications

The Relationship Between Toxoplasmosis and Concentration of Prolactin and Progesterone in Pregnant Women

The Relationship Between Toxoplasmosis and Concentration of Prolactin and Progesterone in Pregnant Women

Toxoplasmosis Screening during Pregnancy in a Romanian Infectious Diseases Tertiary Center: Results of a 15 Years Follow-Up Program

Effects of different drugs and hormone treatment on Toxoplasma gondii glutathione S-transferase 2

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