Background. Currently, exploring effective agents is urgently required for polycystic ovary syndrome (PCOS) treatment. Although nourishing kidney promoting ovulation decoction (NKPOD) as a traditional Chinese medicine decoction is widely employed to increase pregnancy rates, whether NKPOD attenuates ovulation disorders in PCOS patients remains unknown. Here, we aim to explore the clinical significance and the underlying mechanisms of NKPOD in ovulation disorders. Methods. PCOS patients were recruited to confirm the clinical significance of NKPOD in attenuating ovulation disorder. Subsequently, regulation targets of NKPOD were identified through network pharmacology analysis. Additionally, a series of experiments were performed to observe the impacts of NKPOD on miRNA-224 transcription through transcription factor AR. Results. In this study, NKPOD administration improved hormone dysregulation and reproductive outcomes in PCOS patients. Interestingly, 100 potential targets related to NKPOD and PCOS were screened, and transcription regulation was observed to be the most enriched function. Mechanistically, NKPOD inhibited miRNA-224 transcription through reducing AR expression, in which AR as a transcription factor directly regulated miRNA-224 transcription. Conclusions. Collectively, these findings highlight the therapeutic effect of NKPOD on PCOS, which could provide promising therapeutic agents for PCOS.
Background
Low fertility and adverse pregnancy outcomes are commonly observed in women with chronic kidney disease (CKD). However, a causal relationship between low fertility and adverse pregnancy outcomes with CKD remains unclear. Besides, whether mild kidney dysfunction can affect fertility and pregnancy still needs exploration. Hence, this study aimed to investigate the causal effect of kidney damage on fertility and pregnancy using Mendelian randomization (MR).
Methods
We first used two-sample MR to examine the effects of kidney damage on fertility and pregnancy. Next, we introduced the Bayesian model averaging MR analysis to detect major causal relationships and render the results robust. The genetic instruments and outcome data were derived from various large genome-wide association studies.
Results
Adverse pregnancy outcomes: Our analyses supported a suggestive causal effect of CKD and estimated glomerular filtration rate (eGFR) rapid on stillbirth, with CKD having an odds ratio (OR) of 1.020 [95% confidence interval (CI) 1.002 to 1.038] and eGFR rapid having an OR of 1.026 (95% CI 1.004–1.048). We also discovered a suggestive causal effect of eGFR on spontaneous abortion, with an OR of 2.63 (95% CI 1.269 to 5.450). Moreover, increased urinary albumin-to-creatinine ratio (UACR) was regarded as a potential risk factor for pre-eclampsia (OR = 1.936; 95% CI 1.065 to 3.517) and gestational hypertension (OR = 1.700; 95% CI 1.002 to 2.886). Fertility assessment: The results indicated that eGFR and UACR had a suggestive causal relationship with the anti-Müllerian hormone level (eGFR beta: 1.004; UACR beta: 0.405).
Conclusions
Our study used MR to demonstrate a suggestive causal relationship between kidney damage and fertility and pregnancy. We reported that mild kidney dysfunction might be a risk factor for reduced fertility and adverse pregnancy outcomes. Dynamic renal detection may help preserve fertility and reduce the risk of pregnancy loss.
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