Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages

Rahman, Tanzil Ur; Ullah, Kalim; Guo, Mingxiao; Pan, Haitian; Liu, Juan; Ren, Jun; Jin, Long-Fei; Zhou, Yi‐Chao; Cheng, Yi; Sheng, Jian‐Zhong; Huang, He‐Feng

doi:10.18632/oncotarget.24821

Cited by 15 publications

(10 citation statements)

References 47 publications

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“…The proteins of the upstream regulators also play key roles in RM. Furthermore, p38 MAPK gene delays the implantation process by blocking these specific genes [19]. In the present study, proteomics analysis also showed that the p53 gene pathway was activated by increasing levels of A2, thereby downregulating NUCKS1.…”

Section: Discussionsupporting

confidence: 62%

High androgen level causes recurrent miscarriage and impairs endometrial receptivity

Su¹,

Shi²

2021

Trop. J. Pharm Res

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Purpose: To investigate the effect of androgen (A2) at different concentrations on human endometrial epithelial cancer cell line (HHUA) using iTRAQ and liquid chromatography–mass spectrometry (LCMS/MS) analysis. Methods: Human endometrial cells were cultured in Dulbecco Modified Eagle Medium. Total protein was isolated from human endometrial cells and HHUA cells were treated with A2 in three different concentrations (10-9 , 10-8 and 10-7 M). The proteins were digested using filter-aided sample preparation (FASP) method, and labeled using iTRAQ. The proteins were then subjected to LC-MS/MS. The resultant peptides were identified using Expasy tool, and the up-stream and down-stream proteins were confirmed. Moreover, the up-regulated proteins: isoform 2 of nuclear ubiquitous casein and cyclindependent kinase substrate 1 (NUCKS1), isoform 2 of endothelial differentiation-related factor 1 (EDF1), and acid phosphatase 1 (ACP1) were independently confirmed using western blotting and immunohistochemistry techniques. Results: Transforming growth factor (TGF), p38 mitogen-activated protein kinase (p38-MAPK), cyclindependent kinase (CDK), and tumor protein p53 (TP53) were the major regulators of the upstream process, and were upregulated RM-linked endometrial epithelial cells. Androgen-associated proteins NUCKS1, EDF1, and ACP1 were significantly responsible for miscarriage-related changes in endometrial tissues (p < 0.05). The results showed that a high level of androgen significantly (p < 0.05) distorts the expression levels of proteins associated with endometrium development, resulting in impaired endometrial accessibility which led to miscarriage. Conclusion: Androgen-associated proteins are responsible for changes in endometrial tissues which, in turn, lead to recurrent miscarriage.

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Section: Discussionsupporting

confidence: 62%

High androgen level causes recurrent miscarriage and impairs endometrial receptivity

Su¹,

Shi²

2021

Trop. J. Pharm Res

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“…In 1988, Sagle et al [ 92 ] reported a high prevalence of PCOM in women who had recurrent miscarriages, which was later confirmed by other authors [ 93 ]. Additionally, available data emphasize the impact of HA on miscarriages [ 94 , 95 , 96 , 97 ], but the role of adrenal androgens has not been studied widely [ 98 , 99 , 100 ]. Moreover, reports concerning the predictive value of LH on miscarriage are distinct [ 93 , 101 , 102 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Ageing on Clinical, Hormonal and Sonographic Features Associated with PCOS—A Long-Term Follow-Up Study

Jacewicz-Święcka

Wołczyński

Kowalska

2021

JCM

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The knowledge of polycystic ovary syndrome (PCOS) natural history is limited. Our objective was to assess the effect of aging on clinical, hormonal and sonographic ovarian PCOS features and additionally to identify parameters that impact the course of PCOS. A secondary aim was to supply additional information on the reproductive outcome in women with previously diagnosed PCOS. A longitudinal cohort study with a median follow-up of 120.9 months was conducted, and 31 Caucasian women previously diagnosed with PCOS according to the Rotterdam criteria were re-examined at a median age of 35. Clinical examinations; transvaginal ultrasound scans; and lipid, E-selectin and sex hormone assessments were performed at the beginning and at the end of the follow-up. It was observed that menstrual cycles became regular and sonographic morphology of ovaries was normalized in 55% and 49% of the participants, respectively (all p < 0.05). At the final assessment, 55% of the women no longer met the criteria for PCOS (p < 0.05). The age, follicle-stimulating hormone (FSH) and E-selectin assessed at the baseline were the most important predictors of the PCOS persistence into later years (respectively, OR = 0.84, OR = 0.39, OR = 1.08, all p < 0.05). Ninety-five percent of the patients who had ever been trying to conceive became pregnant a minimum of once. The women with persistent PCOS had worse metabolic and reproductive parameters compared to the women with resolved PCOS. Positive correlations were found between the number of miscarriages and ovarian volume, LH, androstenedione, 17-hydroxyprogesterone and an increase in E-selectin during the follow-up (R = 0.46, R = 0.59, R = 0.54, R = 0.49, R = 0.47, all p < 0.05). In conclusion, progressing from the third to the fourth decade is connected with a reduction in PCOS features, which seems to have a great impact on fertility of women with a previous diagnosis of PCOS. FSH and E-selectin, as determined at the initial PCOS diagnosis, had an impact on the disappearance of the syndrome years after.

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“…The retrospective nature of our study could be a limitation. Besides, the previous studies showed that excess androgen could also cause adverse effects on the reproductive outcome of IVF‐ET 23,24 . These paradoxical phenomena reveal that endometrial development and embryonic implantation of patients with severe endometriosis may require appropriate basal serum androgen concentration which needs further investigation.…”

Section: Discussionmentioning

confidence: 98%

Low basal serum testosterone level is detrimental to the embryo implantation in the patients with severe endometriosis

Huang

Chen

Long

et al. 2021

J of Obstet and Gynaecol

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Aim Androgens have been reported to be associated with female fertility. The mean serum testosterone concentration in the patients with endometriosis was reported to be significantly lower than that without endometriosis. Our study was designed to investigate the influence of basal serum testosterone levels on the clinical outcome of in vitro fertilization (IVF) in the patients with III‐IV stage endometriosis. Methods This retrospective cohort study included 407 patients with III‐IV stage endometriosis diagnosed by laparoscopic surgery. We studied the association of the basal serum testosterone level and the reproductive outcome of IVF. Results The basal serum testosterone concentration was significantly higher in the pregnant group of patients with III‐IV stage endometriosis. The further analyses demonstrated that the implantation rate of the basal serum testosterone concentration < 0.305 ng/mL group was significantly lower than the testosterone ≥ 0.305 ng/mL group (24.1% vs. 32.7%, p = 0.007). The clinical pregnancy and live birth rate of the basal serum testosterone < 0.305 ng/mL group were also lower than that of the testosterone ≥ 0.305 ng/mL group. Both initial and total dose of gonadotropins in the testosterone <0.305 ng/mL group are significantly higher than that of the testosterone ≥0.305 ng/mL group. Conclusions Our study demonstrated, for the first time, that the basal serum testosterone <0.305 ng/mL had an adverse impact on pregnancy outcomes of IVF‐embryo transfer in the patients with III‐IV stage endometriosis. Besides, the basal serum testosterone is also helpful in making individual stimulation protocol for the patients with advanced endometriosis before entering IVF cycles.

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Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages

Cited by 15 publications

References 47 publications

High androgen level causes recurrent miscarriage and impairs endometrial receptivity

High androgen level causes recurrent miscarriage and impairs endometrial receptivity

The Effect of Ageing on Clinical, Hormonal and Sonographic Features Associated with PCOS—A Long-Term Follow-Up Study

Low basal serum testosterone level is detrimental to the embryo implantation in the patients with severe endometriosis

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