Treatment with mifepristone in combination with misoprostol may be a safe and less expensive option compared with surgical management in missed miscarriage, but the efficacy of medication management varies in clinical practice. This study aims to identify the risk factors related to successful medical management using mifepristone and misoprostol for missed miscarriage. We carried out a retrospective case-control study in the First Affiliated Hospital with Nanjing Medical University from January 1, 2023 to December 31, 2023. Patients were recruited into this study if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 13 weeks of pregnancy (by last menstrual period), and chose to have medication management. Women who failed to spontaneously pass the gestational sac within 24 h of the oral misoprostol dose were included in the case group, while women who had complete gestational sac expulsion within 24 h of the oral misoprostol dose were defined as controls. The baseline characteristics of the patients were collected in the electronic medical record system and the meteorological data were obtained from the Nanjing Meteorological Observation Centre. Logistic regression analysis was used to identify the risk factors which affected medication management efficacy. A total of 163 patients met inclusion criteria, including 60 patients in the case group and 103 patients in the control group. Our results showed that the history of gravidity, history of parity, history of miscarriage, history of caesarean section, prior uterine surgery, and the use of supplemental vaginal misoprostol could be potential risk factors, while the remaining variables showed no significant differences between the two groups. The univariable logistic regression model demonstrated that the risk of unsuccessful medication management was increased 3.67-fold in patients who had been pregnant more than 3 times (95

Premature ovarian insufficiency (POI) is a condition identified by the decline in ovarian function before the age of 40. The treatment of POI patients deserves in-depth research. This study aimed to explore the impacts of probiotics on the gut and vaginal microbiota, ovarian function and metabolic indexes in a mouse model of POI. A mouse model of POI was successfully established by intraperitoneal injection of cyclophosphamide. Subsequently, the mice were divided into the control group, the POI group and the POI gavage group. Mice in the POI gavage group were gavaged for 28 consecutive days with a mixture of 12 probiotics. The anti-Müllerian hormone (AMH) and sex hormone levels, the number of follicles, the serum total cholesterol (TC) and triglycerides (TG) levels and the distributions of gut and vaginal microbiota of the mice were assessed and compared. Compared with the healthy control group, the level of AMH and the number of growing follicles significantly decreased in POI mice (P<0.05), whereas the number of atretic follicles increased significantly (P<0.05). Meanwhile, the gut and vaginal microbiotas were disturbed in the POI group. Bacterial genera such as Allobaculum, Prevotella and Bacteroides were enriched in the gut microbiota, while Proteus, Streptococcus and Rothia were enriched in the vaginal microbiota. However, these bacteria contributed no favorable effect on the host. Interestingly, the increases in these taxa were reversed in POI mice treated with probiotics. Additionally, although there were no significant differences in AMH, estradiol (E2), and follicle stimulating hormone (FSH) levels between POI group without probiotics and POI gavage group (P>0.05), the AMH and E2 levels tended to increase while the FSH level tended to decrease in the gavage group. Besides, the number of growing follicles in the gavage group exhibited a slight increase compared with the POI group without probiotics (P>0.05), whereas the number of atretic follicles in the gavage group showed a decrease (P>0.05). Moreover, the levels of TC and TG in POI group without probiotics were elevated compared with the control group, while this trend was reversed in the POI gavage group (TG: P<0.05, TC: P>0.05). Probiotics may mitigate vaginal microbiota disruption, alleviate lipid metabolism disorders and improve indicators related to ovarian function by modulating the dysbiosis of gut microbiota in POI mice. These results provide some new directions and theoretical foundations for future microecological treatment in POI patients in clinical practice.

The widespread contamination of polystyrene nanoparticles (PS-NPs) has emerged as a significant global concern due to its potential threats to human and animal health. Although the toxicity of PS-NPs to ovarian function has been established, how to relieve the damage of PS-NPs to oocyte maturation remains elusive. Since melatonin (MLT) plays an essential role in regulating ovarian function. This study is the first attempt to explore the protective roles of melatonin in counteracting the maturation defects of oocytes caused by PS-NPs exposure. In this investigation, the reproductive toxicity of PS-NPs was evaluated after continued exposure for 35 days. After exposure, cumulus oocyte complexes (COCs) obtained from PS-NPs exposed-mice were cultured in vitro, meanwhile the various concentration MLT were supplemented into the culture medium to determine the beneficial roles. The results revealed that PS-NPs exposure could impede the meiotic progression, fertilization competence and subsequent embryonic development of oocytes. These impairments are likely mediated through multiple mechanisms, including excessive ROS generation, reduced ATP contents, mitochondrial dysfunction and subsequent induction of early apoptosis. Besides, PS-NPs exposure was found to compromise the architecture of spindle and the alignment of chromosome via altering the key epigenetic markers (tubulin-ace and H4K12ac). Notably, these adverse effects could be alleviated after MLT administration. Further analysis demonstrated that MLT supplementation significantly enhanced antioxidant capacity and mitochondrial dynamics, which indicated by enlarged the mRNA expression levels of anti-oxidative enzyme and mitochondrial dynamics-related genes. In conclusion, MLT could rescue PS-NPs-induced oocyte quality decline by ameliorating oxidative stress, restoring mitochondrial function, and normalizing epigenetic modifications.

Background:Primary ovarian insufficiency (POI), a cause of female infertility, is characterized by elevated gonadotropin levels and fluctuating estrogen reductions, accompanied by irregular menstruation, osteoporosis, cardiovascular disease, and genitourinary syndrome of menopause. Previous studies have shown an association between POI and immune cells, but the causal relationship remains unclear. Sex hormones play a crucial role in immune regulation by influencing the function and levels of immune cells, suggesting they may be key mediators between POI and immune cells. Methods:Utilizing genome-wide association studies (GWAS), we conducted a comprehensive bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationship between 731 immune cell traits and POI. Furthermore, a two-step MR analysis was employed to examine the potential mediating effects of sex hormones between these two systems. To ensure the robustness of our findings, we performed extensive sensitivity analyses, evaluating heterogeneity and horizontal pleiotropy. Results:After FDR adjustment (PFDR < 0.05), ten immune cell phenotypes were significantly correlated with the risk of POI. Among these, one immune cell phenotype was identified as a risk factor for POI (OR > 1), while the other nine immune cell phenotypes were protective factors (OR < 1). In the reverse MR analysis, POI was positively correlated with seven immunocyte phenotypes (OR > 1) and negatively correlated with eleven immunocyte phenotypes (OR < 1). No potential mediating effects of ten sex hormones were found between POI and immune cell traits. Conclusions:Our study comprehensively assessed the correlation between immune cell phenotypes and POI in the European population, excluding the mediating role of sex hormones, thus providing valuable insights into the biological mechanisms of POI and informing early prevention and treatment strategies.

系统性红斑狼疮是一种致病性自身抗体和免疫复合物形成并介导器官、组织损伤的慢性自身免疫病。狼疮累及心脏瓣膜可产生非感染性疣状赘生物，称为Libman-Sacks心内膜炎。Libman-Sacks心内膜炎的诊断及治疗方案目前尚无指南推荐。该文报道狼疮肾炎合并Libman-Sacks心内膜炎1例，为Libman-Sacks的诊治提供一定的经验及依据。.

The reproductive lifespan of female mammals is determined by the size of the primordial follicle pool, which comprises oocytes enclosed by a layer of flattened pre-granulosa cells. Oocyte differentiation needs acquiring organelles and cytoplasm from sister germ cells in cysts, but the mechanisms regulating this process remain unknown. Previously helicase for meiosis 1 (HFM1) is reported to be related to the development of premature ovarian insufficiency. Here, it is found that HFM1 is involved in oocyte differentiation through organelle enrichment from sister germ cells. Further study indicates that HFM1 is involved in intercellular directional transport through intercellular bridges via the RAC1/ANLN/E-cad signaling pathway, which is indispensable for oocyte differentiation and primordial follicle formation. These findings shed light on the critical role of HFM1 in intercellular bridge transport, which is essential for the establishment of the primordial follicle pool and presenting new horizons for female fertility protection.

BACKGROUND:Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.RESULTS:The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.CONCLUSIONS:These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.

Premature ovarian insufficiency (POI) is defined as the depletion of ovarian function before the age of 40 years. The global prevalence of POI is 3.5%. To date, genetic factors account for 23.5% of the etiology of POI. Herein, a previously uncharacterized pathogenic homozygous variant of the chromosome segregation-1-like gene (CSE1L) was identified in POI patients via targeted panel sequencing. It is reported that dysregulated iron metabolism is involved in many reproductive endocrine disorders; however, its precise role in POI remains obscure. In this study, we identified CSE1L as a potential candidate gene that plays an important role in maintaining iron homeostasis. Deficiency of CSE1L led to ferroptosis in human granulosa cells, which was confirmed by transmission electron microscopy. Mechanistically, coimmunoprecipitation identified the direct interaction between CSE1L and FoxO1. Inhibition of CSE1L led to the excessive accumulation of FoxO1 in the nucleus via nucleocytoplasmic transport. Then, FoxO1 bound to the promoter region of NCOA4 and promoted its transcription, which was verified by a chromatin immunoprecipitation assay. Moreover, inhibition of CSE1L in cumulus cell monolayer could impede oocyte maturation, which might be associated with oxidative stress. Consequently, our study first revealed that CSE1L participated in ferroptosis in human ovarian granulosa cells via nucleocytoplasmic transportation, which might be helpful in revealing the molecular mechanism of CSE1L in the development of POI. Importantly, these findings might provide new insights into the application of ferroptosis inhibitors in the treatment of POI.

BACKGROUND:Postpartum psychiatric disorders (PPDs) have been deemed as a significant public health concern, affecting both maternal health and family dynamics. This study aimed to examine the current status of PPDs, identify the potential risk factors of PPDs, and further develop a clinical nomogram model for predicting PPDs in Chinese women. METHOD:In this retrospective cohort study, 1418 postpartum women attending the routine postpartum examination at the 42nd day after delivery in Jiangsu Women and Children Health Hospital were recruited as participants from December 2020 to December 2022. The Symptom Checklist-90 (SCL-90) was utilized to assess the status of postpartum psychiatric disorders. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The relationships between predictive factors of PPDs and SCL-90 were also evaluated using Pearson correlation analysis. The relationships between predictive factors of PPDs and SCL-90 were evaluated using Pearson correlation analysis. RESULTS:With the SCL-90 cutoff value of 160, the incidence of postpartum psychiatric disorders was 9.17% among Chinese urban women. The univariate and multivariate logistic regression analyses indicated that age ≤ 25 years old (OR = 10.07, 95%CI = 1.83-55.33), prenatal mood disorder (OR = 4.12, 95%CI = 1.99-8.53), invasive prenatal diagnostic procedures (OR = 4.39, 95%CI = 1.16-16.56), poor relationship with husband (OR = 2.86, 95%CI = 1.58-5.16) and poor relationship with mother-in-law (OR = 5.10, 95%CI = 2.70-9.64) were significantly associated with PPDs. A nomogram prediction model for PPDs was further constructed based on these five independent risk factors, and the area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.823 (95% CI = 0.781-0.865). The calibration curves showed remarkable accuracy of the nomogram and the DCA exhibited high clinical net benefit of the nomogram. Besides, we also explored the relationships between the five risk factors and different symptom dimensions of PPDs and found that the five risk factors were almost associated with increased levels of all symptom dimensions. CONCLUSIONS:Five psychosocial risk factors for PPDs were identified in Chinese women and the nomogram prediction model constructed based on these five risk factors could predict the risk of PPDs intuitively and individually. Systematic screening these risk factors and further conducting psychosocial interventions earlier during the pregnancy period are crucial to prevent PPDs. For future research, we intend to incorporate additional risk factors, including blood biomarkers and facial expression indicators, to refine our risk model.

目的 探讨江苏地区孕妇全孕期增补叶酸对妊娠期糖尿病(GDM)的影响.方法 选取2017年1月至2018年12月间在江苏省分娩的胎龄≥28周的产妇.根据是否服用叶酸分为未服叶酸组和服用叶酸组.根据服用叶酸的剂量和时间分为六组:早孕期单纯0.4 mg/d叶酸(0.4 mg叶酸)组、早孕期含叶酸0.4 mg/d的复合维生素(MV+0.4 mg叶酸)组、早孕期含叶酸0.8 mg/d的复合维生素(MV+0.8 mg叶酸)组、全孕期单纯0.4 mg/d叶酸(0.4 mg叶酸)组、全孕期含叶酸0.4 mg/d的复合维生素(MV+0.4 mg叶酸)组、全孕期含叶酸0.8 mg/d的复合维生素(MV+0.8 mg叶酸)组.通过问卷调查表,由培训专员收集并记录产妇的一般情况、叶酸增补情况、孕产史、职业和环境因素及GDM等信息.应用logistic回归及χ2检验等方法对全孕期叶酸增补情况与GDM的相关性进行统计分析.结果 共纳入10662例产妇,未服叶酸组与服用叶酸组GDM的发生率分别为9.7％(100/1028)、10.5％(1014/9634),差异无统计学意义.与未服叶酸组相比,无论是否校正协变量,全孕期增补叶酸的女性发生GDM的风险显著增加,尤其是年龄小于35岁、孕前体质量指数(BMI)在正常范围及有分娩史的女性.结论 孕期叶酸增补应适量,全孕期增补叶酸的女性发生GDM风险增加.

Objective:To evaluate the correlation between the percentage of body fat（PBF） and the triglyceride（TG）level of pregnant women and their gestational diabetes mellitus(GDM.Methods:81 pregnant women with GDM who received prenatal care in hospital were included in study group,and 162 healthy pregnant women matching as 1:2 in age and weight were recruited in control group from January to October 2021.The PBF during the first trimester of pregnancy and the TG level during the second trimester of pregnancy of the women were compared between the two groups.The influencing factors of GDM of the women were analyzed.The predictive values of the PBF and TG level of the pregnant women for their GDM were evaluated.Results:The PBF（34.9±5.2 %） and the TG level（2.4±0.8）mmol/L of the women in the study group were significantly higher than those（30.0±4.8% and 1.9±0.6 mmol/L） of the women in the control group（P＜0.05）.The ratios of the women with PBF＞33.6%（48.1 %） and with the TG level ＞2.3 mmol/L（49.4%） in the study group were significantly higher than those（21.6% and 20.4%） in the control group（P＜0.05）.Multivariate logistic regression analysis showed that the PBF＞33.6% and the TG level＞2.30mmol/L of the women were the independent risk factors of their GDM occurrence（P＜0.05）.The risk of GDM occurrence of the women with the PBF＞33.6% and the TG level ＞2.30 mmol/L was 8.005 times of the women with the PBF≤33.6% and the TG level≤2.30 mmol/L（95%CI 3.006-18.662）.The interaction attribution percentage（AP） of the PBF and the TG level for GDM was 0.632（95 % CI 0.224-1.039）.The area under the curve,the sensitivity,the specificity,and Yoden index of the PBF and the TG level combined with the conventional risk factors for predicting GDM were 0.791（95%CI 0.734-0.849）,80.9%,60.5%,and 0.414,respectively.Conclusion:The high PBF and the high TG level of the women during pregnancy are relevant to the increased risk of their GDM occurrence.The PBF and the TG level may have synergistic effect on the development of GDM,and which combined with the conventional risk factors has certain predictive value for the occurrence of GDM.

Objective:To explore the effects of long-term and low-dose cypermethrin（CYP） exposure on ovarian function in mice.Methods:Fifteen 17-19 g, 3-week old ICR female mice were randomly assigned into three groups with 5 mice for each group: the very low-dose group, the low-dose group and the control group, and the mice were exposed to 0.02 mg·kg -1 ·d -1 CYP,0.2 mg·kg -1 ·d -1 CYP and 0.01% absolute ethanol respectively for six months. At the 6 th month, the estrous cycle, serum levels of FSH and anti-Mullerian hormone（AMH） in mice were observed, and unilateral ovaries were isolated for follicles counting. Moreover, the immature cumulus oocyte complexes（COCs） were extracted after intraperitoneal injection of 10 U of pregnant horse serum gonadotropin（PMSG） into 3-week old ICR female mice for 46 to 48 hours. Then, the COCs were randomly divided into three groups, the COCs in the control group, very low-dose group and low-dose group were exposed to CYP at doses of 0 μmol/L,100 μmol/L and 200 μmol/L. After 16-18 hours, the number of MⅡ oocytes was counted, and the expulsion rate of the first polar body（PB1）,reactive oxygen species（ROS） and mitochondrial membrane potential of each group were analyzed.Results:The results of in vivo experiments showed that the body weight and uterine coefficient of mice in the very low dose group and the low dose group did not significantly change, while the ovarian coefficient slightly decreased, but the difference was not significant（P＞0.05）. Compared with the control group, the estrous cycle of mice in the low dose group was disordered, serum FSH levels [（17.53±4.04） U/L vs.（5.67±0.52） U/L,P＜0.05] were significantly increased, AMH levels [（0.47±0.15）ng/ml vs.（1.41±0.24）ng/ml, P＜0.05] were significantly decreased, and the number of antral follicles [（22.80±4.49） vs.（84.00±14.98）,P＜0.05] were significantly decreased, but there was no significant difference in number of follicles at other stages（P＞0.05）. The results of in vitro experiments showed that compared with the control group, the PB1 expulsion rate and mitochondrial membrane potential were significantly decreased, and the level of ROS in oocytes was significantly increased in the low-dose group（P＜0.05）.Conclusions:Long-term and low-dose cypermethrin(0.2 mg·kg -1 ·d -1 ) exposure may leads to diminished ovarian reserve by affecting the development of oocyte.

目的:分析功能性下丘脑性闭经(FHA)患者的体成分特点.方法:选择2016年6月-2022年6月本院确诊的101例FHA患者为观察组,并选择同期进行健康体检、月经正常的101例年龄匹配的女性为对照组.记录研究对象的年龄、身高、体重,应用人体成分分析仪对其进行人体成分检测,比较两组各项指标的差异,并根据身体质量指数(BMI)进一步分层分析.结果:两组的年龄比较无统计学差异,但FHA组的身高高于对照组,体重低于对照组(P＜0.05).FHA 组 BMI[(19.53±2.95)kg/m2 比(22.14±4.55)kg/m2]、腹围[70.2(65.9,74.4)cm 比 76.6(73.3,83.7)cm]、全身脂肪含量[11.5(8.4,15.3)kg 比 15.9(13.0,21.2)kg]、内脏脂肪面积[47.5(34.8,64.3)cm2 比 65.8(54.9,84.8)cm2]、体脂率[(23.18±7.80)％比(30.87±7.39)％]均显著低于对照组(均P＜0.05),但两组对象的骨骼肌含量、基础代谢率、蛋白质含量无明显差异.FHA组中体重过低(BMI＜18.5 kg/m2)女性所占比例显著高于对照组(34.6％比17.8％),超重/肥胖女性(BMI≥24 kg/m2)占比低于对照组(9.9％比23.76％)(均P＜0.01),而体重正常女性(18.5 kg/m2≤BMI＜24.0 kg/m2)在两组中占比相似(55.4％比58.4％).进一步按BMI分层分析发现,FHA组中各亚组全身脂肪含量、内脏脂肪面积、体脂率仍显著低于对照组(均P＜0.05).结论:FHA患者中体重过低女性占比较高,且其体脂率在不同BMI组别中明显低于月经正常女性.建议对FHA患者进行体成分分析,更全面地评估营养状况,进而为她们提供个体化营养膳食指导,科学增加体重及体脂率,促进月经恢复.

The aim of this systematic review and meta-analysis is to evaluate the efficacy of stem cell therapy in mouse models of POI and patients with POI. The PubMed, Web of Science, and Embase databases were searched from inception to February 2022 for relevant animal and clinical studies. The reference lists of the included reviews were manually searched to identify additional eligible studies. Data were independently extracted by two investigators, and disagreements were resolved by discussion. SYRCLE’s risk of bias tool and the MINORS tool were used to assess the quality of animal and clinical studies by two independent investigators. All statistical analyses were conducted using Review Manager 5.3 software. A total of twenty animal studies and six clinical studies were included in this meta-analysis. In animal studies, the results showed that stem cells could improve hormone levels, follicle count, estrous cycle and pregnancy outcome. For hormone levels, stem cells increased serum E2 and AMH levels and decreased serum FSH and LH levels compared with the control group (serum E2 level: SMD: 5.05, 95% CI 4.21–5.90, P < 0.00001; serum AMH level: SMD: 4.42, 95% CI 3.06–5.79, P < 0.00001; serum FSH level: SMD: − 3.79, 95% CI − 4.87 to –  2.70, P < 0.00001; serum LH level: SMD: − 1.31, 95% CI − 1.65 to − 0.96, P < 0.00001). All follicle counts, except for the antral follicle count, were significantly changed compared with the control group. (primordial follicle count: SMD: 4.61, 95% CI 3.65–5.56, P < 0.00001; primary follicle count: SMD: 3.35, 95% CI 1.08–5.63, P = 0.004; secondary follicle count: SMD: 3.23, 95% CI 1.92–4.55, P < 0.00001; total follicle count: SMD: 4.84, 95% CI 2.86–6.83, P < 0.00001; oocyte count: SMD: 7.56, 95% CI 5.92–9.20, P < 0.00001; atretic follicle count: SMD: − 1.79, 95% CI − 2.59 to − 1.00, P < 0.00001). For the estrous cycle, stem cell therapy increased the number of estrous cycles (WMD: 2.72, 95% CI 2.07–3.37, P < 0.00001) and decreased the duration of the estrous cycle (WMD: − 1.26, 95% CI − 1.84 to − 0.69, P < 0.0001) compared with the control group. For pregnancy outcomes, stem cell therapy increased the fertility rate (RR: 3.00, 95% CI 1.74–5.17, P < 0.0001) and litter size (WMD: 3.82, 95% CI 0.36–7.28, P = 0.03) compared with the control group. In animal studies, the asymmetric funnel plot of serum E2 and FSH levels indicated the possibility of publication bias. Unpublished and negative studies may be the source of publication bias. In clinical studies, the results showed that stem cell therapy could decrease serum FSH level (MD: − 30.32, 95% CI − 59.03 to − 1.01, P = 0.04) and increase AFC (MD: 1.07, 95% CI 0.70–1.43, P < 0.00001), pregnancy rate (RD: 0.19, 95% CI 0.04–0.34, P = 0.01) and live birth rate (RD: 0.19, 95% CI 0.07–0.31, P = 0.001) in POI patients. In addition, there was no significant difference in menstrual function regained (RD: 0.22, 95% CI − 0.03–0.46, P = 0.09), oocytes retrieved (MD: 1.00, 95% CI − 0.64–2.64, P = 0.23) and embryos (MD: 0.80, 95% CI − 0.15–1.76, P = 0.10) between different groups. This meta-analysis suggested that stem cell therapy might be effective in POI mouse models and patients and could be considered a potential treatment to restore fertility capability in POI patients.

Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function before the age of 40 years. It is confirmed to have a strong and indispensable genetic component. Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a key inducer of mitochondrial protein quality control for the clearance of misfolded or damaged proteins, which is necessary to maintain mitochondrial function. Previous findings have shown that the variation in CLPP is closely related to the occurrence of POI, which is consistent with our findings. This study identified a novel CLPP missense variant (c.628G > A) in a woman with POI who presented with secondary amenorrhea, ovarian dysfunction, and primary infertility. The variant was located in exon 5 and resulted in a change from alanine to threonine (p.Ala210Thr). Importantly, Clpp was mainly localized in the cytoplasm of mouse ovarian granulosa cells and oocytes, and was relatively highly expressed in granulosa cells. Moreover, the overexpression of c.628G > A variant in human ovarian granulosa cells decreased the proliferative capacity. Functional experiments revealed that the inhibition of CLPP decreased the content and activity of oxidative respiratory chain complex IV by affecting the degradation of aggregated or misfolded COX5A, leading to the accumulation of reactive oxygen species and reduction of mitochondrial membrane potential, ultimately activating the intrinsic apoptotic pathways. The present study demonstrated that CLPP affected the apoptosis of granulosa cells, which might be one of the mechanisms by which CLPP aberrations led to the development of POI.