iScience
·
2023
·
IF 5.8
Yating Xie,Wenya Guo,Xi Shen,Weina Yu,Yanping Kuang,Qiuju Chen,Hui Long,Qifeng Lyu,Li Wang
Summary Progestin-primed ovarian stimulation (PPOS) is a new ovulation stimulation protocol, and its role in ovulation and regulatory mechanism is unclear. The clinical PPOS protocol was simulated in mice. The ovulated oocytes, estradiol, progesterone, and luteinizing hormone (LH) levels were analyzed at different hours after trigger. mRNA extraction and real-time PCR, hematoxylin and eosin staining, and immunofluorescence of ovaries were used to explore the involved signaling pathways. The PPOS group had a delayed ovulation at 12.5 h after trigger. Its suppressed LH level reduced the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) on the preovulatory follicles before trigger and significantly decreased the following progesterone synthesis, blood progesterone level, and progesterone receptor (PGR) expression within 4–6 h after trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS-1, VEGF-A, and EDN2 were downregulated, ultimately delaying the ovulation. PPOS suppresses the LH level before trigger and decreases the synthesis of progesterone after trigger, thus delaying the ovulation by downregulating the LHCGR-PGR pathway.
研究领域:
生殖生物学
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内分泌学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 7
·5081
·
IF 1.6
Pengyu Huang,Suhua Jiang,Beihong Zheng,Yun Fu,Wenqiang You,Haiyan Li
Objective: To evaluate the therapeutic outcomes of combining ethinylestradiol-cyproterone acetate (EE-CPA) with raloxifene in the management of polycystic ovary syndrome (PCOS)-associated infertility. Methods: The study included 115 women diagnosed with PCOS-associated infertility, admitted between January 2021 and January 2025. The participants were divided into two groups: 55 women receiving raloxifene monotherapy (control group) and 60 treated with EE-CPA plus raloxifene (observation group). The following were assessed: therapeutic effectiveness, adverse drug reactions (abdominal/pelvic pain, nausea/vomiting, body weight fluctuations, and breast tenderness), metabolic markers (fasting plasma glucose [FPG], fasting serum insulin [FINS], and homeostasis model assessment of insulin resistance [HOMA-IR]), sex hormones (estradiol [E2], follicle-stimulating hormone [FSH], and luteinizing hormone [LH]), ovarian function (ovarian volume and endometrial thickness), endometrial receptivity (resistance index [RI] and pulsatility index [PI]), and pregnancy outcomes (ovulation, miscarriage, and clinical pregnancy). Results: The combination therapy showed superior outcomes, including enhanced overall effectiveness, increased ovulation and pregnancy rates, and a reduced miscarriage rate (all P>0.05). No significant differences in adverse drug reactions were found between the two groups (P>0.05). After treatment, the observation group showed greater improvements in metabolic markers, FSH, LH, ovarian volume, RI, and PI (all P>0.05). Additionally, E2 levels and endometrial thickness were more significantly enhanced in the observation group compared to the control group (all P>0.05). Conclusions: The combination of EE-CPA and raloxifene is highly effective in managing PCOS-associated infertility, improving therapeutic outcomes without significantly increasing adverse effects. It also leads to notable improvements in metabolism, sex hormones, ovarian function, and endometrial receptivity, ultimately enhancing pregnancy outcomes.
研究领域:
妇产科学
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内分泌学
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生殖医学
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药理学
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临床研究
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产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2025
·Vol. 18
·期 1
·1-14
·
IF 4.2
Zheng Xiufen,Chen Zikai,Liang Miao,Zhou Liting,Wang Miaoru,Zhang Silin,Zhang Shuyun,Ma Lei,Yi Wei,Liu Xiawen
Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects. This study investigates the role of UGT2B15, an essential enzyme for androgen metabolism, in PCOS pathogenesis and its potential as a therapeutic target.Methods We used RNA sequencing to examine the effects of UGT2B15 knockdown in KGN cells. To modulate UGT2B15 expression, we employed siRNA and (R)/(S)-NAF (naftopidil), a chemical inducer of UGT2B15 identified in our previous studies on a prostate hyperplasia model. The effects of siRNA and (R)/(S)-NAF on dihydrotestosterone (DHT) levels, cell apoptosis, and the expression of apoptosis-related proteins in KGN cells were evaluated. In a PCOS mouse model, we assessed the effects of (R)-NAF and (S)-NAF on serum androgen levels, menstrual cycles, ovarian morphology, and UGT2Bs expression. Additionally, luciferase reporter and ChIP assays were utilized to study UGT2B15 regulation by NR1H4.Results Elevated androgens were found to suppress UGT2B15 expression in ovarian granulosa cells, leading to DHT accumulation and apoptosis. (R)-NAF and (S)-NAF treatments reversed these effects, alleviating PCOS symptoms in mice such as hyperandrogenism, irregular menstrual cycles, and the presence of ovarian cysts. NR1H4 negatively regulated the transcription of UGT2B15 in KGN cells. (R)-NAF and (S)-NAF disrupted NR1H4 binding to the UGT2B15 promoter without affecting its protein levels, indicating direct interference with its regulation.Conclusion sUGT2B15 represents a promising target for novel PCOS therapies by modulating androgen metabolism and protecting ovarian granulosa cells from apoptosis. (R)-NAF and (S)-NAF regulate UGT2B15 by disrupting NR1H4's binding to its promoter, implying potential therapeutic compounds for PCOS treatment.
研究领域:
内分泌学
·
生殖医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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