Reproductive Sciences最新文献

Polycystic ovary syndrome (PCOS) is a ubiquitous reproductive condition with triggering hallmarks such as glucose intolerance, hyperandrogenism, and dyslipidemia. Despite the existence of various PCOS animal models, an ideal model which could encompass all PCOS-specific phenotype is of dire need. Dehydroepiandrosterone (DHEA) induced PCOS rats are frequently employed; though, determining the superior model among pubertal and prepubertal rats, incorporation of high fat diet (HFD), and their sustainability remains uncertain. This study aims to examine the age factor, impact of HFD, and DHEA regimen in model development. Prepubertal and pubertal Sprague-Dawley rats were subcutaneously injected with DHEA (6 mg/kg and 60 mg/kg/day, respectively) with and without HFD up to 21 days. Serum testosterone, glucose, lipid profile, ovary morphology, and estrous cycle were evaluated. Following 21 days of treatment with DHEA, pubertal PCOS rats exhibited better reproductive phenotype than prepubertal rats. However, there was no significant difference in the lipid profile. Accordingly, both the age-group rats were concomitantly treated with DHEA and HFD for additional 3 weeks on alternate day basis after model development. The persistence of reproductive and metabolic features on treatment withdrawal were also simultaneously investigated by alienating the rats into continuous and stop dosing groups. The DHEA + HFD and DHEA treated pubertal rats in continuous dosing group showed significant PCOS features (p < 0.05) compared to stop dosing, prepubertal, and control groups. To conclude, continual dosing with DHEA on alternate days for 3 weeks is necessary to sustain metabolic and reproductive phenotypes of PCOS.

Bromodomain (BRD)-containing proteins are evolutionarily conserved protein-protein interaction modules involved in many biological processes. BRDs selectively recognize and bind to acetylated lysine residues, particularly in histones, and thereby have a crucial role in the regulation of gene expression. BRD protein dysfunction has been linked to many diseases, including tumorigenesis. Previously, we reported the critical role of BRD-containing protein 9 (BRD9) in the pathogenesis of UFs. The present study aimed to extend our previous finding and further understand the role of the BRD9 in UFs. Our studies demonstrated that targeted inhibition of BRD9 with its potent inhibitor TP-472 inhibited the pathogenesis of UF through increased apoptosis and proliferation arrest and decreased extracellular matrix deposition in UF cells. High-throughput transcriptomic analysis further and extensively demonstrated that targeted inhibition of BRD9 by TP-472 impacted the biological pathways, including cell cycle progression, inflammatory response, E2F targets, ECM deposition, and m⁶A reprogramming. Compared with the previous study, we identified common enriched pathways induced by two BRD9 inhibitors, I-BRD9 and TP-472. Taken together, our studies further revealed the critical role of BRD9 in UF cells. We characterized the link between BRD9 and other vital pathways, as well as the connection between epigenetic and epitranscriptome involved in UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment strategy for this most common benign tumor in women of reproductive age.

Epigenetics impacts male fertility and reproductive disorders. RNA modifications, like m6A, influence RNA metabolism. Varicocele contributes to male infertility, and oxidative stress affects sperm function. This study investigates the expression of key RNA modification enzymes in a rat varicocele model, aiming to elucidate the relationship between varicocele, oxidative stress, and fertility. Fifteen male Wistar rats were divided into Control, Sham, and Varicocele induction groups. Varicocele was induced in the rats surgically. After 8 weeks, testicular tissues and sperm were collected for analysis, including histopathological assessment and evaluation of sperm parameters, functional tests, and gene expression of key RNA modification enzymes: METTL3 as a writer, ALKBH5 and FTO as erasers, and YTHDF2 as a reader involved in recognizing m6A-modified RNA using qRT-PCR. One-way ANOVA with post-hoc Tukey HSD was used for comparing tests within groups. Varicocele induction resulted in histological changes in testicular tissues, including irregularly variable-sized seminiferous tubules. Sperm parameters were significantly affected, with lower concentration, motility, and higher percentage of abnormal sperm in the varicocele group. Increased levels of oxidative stress markers (Sperm lipid peroxidation, and intracytoplasmic ROS) and sperm DNA damage were observed, indicating the presence of oxidative stress in varicocele. Moreover, the expression of key enzymes involved in RNA metabolism was downregulated in the varicocele group. These findings highlight the detrimental impact of varicocele on testicular health, sperm quality, and gene expression, providing insights into the underlying mechanisms of male infertility associated with varicocele.

High intensity focused ultrasound (HIFU) is an effective and safe non-invasive treatment method, widely used in the treatment of uterine fibroids and adenomyosis in the field of gynecology. The side effects in HIFU is low in incidence and mild. HIFU can significantly alleviate the symptoms of patients, reduce lesion volumes, improve quality of life, and has good cost-effectiveness. HIFU can accurately ablate the uterine fibroids and adenomyosis lesions, without destroying normal myometrium and endometrium, and thus HIFU is a promising alternative to myomectomy in uterine fibroids patients with fertility desire. Several studies have shown that in terms of ovarian endocrine function protection, HIFU treatment is superior to uterine artery embolization, and similar to myomectomy. Existing limited researches show that patients with uterine fibroids have a favorable pregnancy rate and live birth rate, as well as a lower natural abortion rate after HIFU treatment. Pregnancy rate after HIFU treatment for uterine fibroids is not lower than myomectomy, and higher than uterine artery embolization. HIFU may have significant advantages in shortening pregnancy interval compared with myomectomy. However, the proportion of cesarean section delivery after HIFU treatment is relatively high, and gestational uterine rupture after HIFU treatment exist in literature. Higher quality clinical data is needed to confirm the pregnancy outcomes and safety after HIFU treatment in future.

Objective: Polycystic Ovary Syndrome (PCOS) is diagnosed by a combination of three features: hyperandrogenism (biochemical and/or clinical), ovulatory dysfunction, and polycystic ovarian morphology, usually detected by ultrasonography. Our study aimed to determine the need for androgen measurements by using hirsutism to establish hyperandrogenism for diagnosing PCOS in a medically unbiased population.

Materials and methods: We utilized a pre-existing cohort of unselected (medically unbiased) females aged 18-45 years. All underwent a history and physical, including a modified Ferriman-Gallwey (mFG) hirsutism score. Subjects were categorized clinically as eumenorrheic non-hirsute (CONTROLS), menstrual dysfunction only (OLIGO-ONLY), hirsutism only (HIRSUTE-ONLY), or menstrual dysfunction and hirsutism (OLIGO + HIRSUTE). All subjects underwent measurements of androgens using high-quality assays. CONTROLS established the upper normal limit for androgen levels. We defined PCOS using the NIH 1990 criteria.

Results: Of 462 individuals with complete evaluations, 311 (67.3%) were CONTROLS, 71 (15.4%) were OLIGO-ONLY, 64 (13.9%) were HIRSUTE-ONLY, and 16 (3.5%) were OLIGO + HIRSUTE. Neither HIRSUTE-ONLY nor OLIGO-HIRSUTE women required androgen measures to demonstrate hyperandrogenism. Among OLIGO-ONLY, 19 (26.8%) demonstrated hyperandrogenemia without hirsutism, with White women significantly more likely than Black women to demonstrate this.

Conclusions: In our study of medically unbiased reproductive-aged women using the NIH 1990 criteria for PCOS, only 15.4% of women evaluated (those with menstrual dysfunction only) required androgen measurements. In these women only one-quarter demonstrated hyperandrogenemia. These data provide a strategy to minimize the need for androgen assays, including firstly categorizing subjects by clinical presentation and then assessing circulating androgens in the subgroup with menstrual dysfunction only.

This study aimed to explore the different characteristics between early-onset severe preeclampsia (ESPE) and late-onset severe preeclampsia (LSPE) to improve pregnancy outcomes. We performed a retrospective cohort study between January 2016 and December 2021. Eligible hospitalized pregnant women with severe preeclampsia were assigned into the early-onset or late-onset group, depending on the gestational age at the time of severe preeclampsia onset (< or ≥ 34 gestational weeks, respectively). The clinical characteristics, laboratory results, maternal complications, and fetal and neonatal outcomes were recorded and compared between the two groups. A total of 1,238 pregnant women were included, with 525 in the early-onset group and 713 in the late-onset group. The late-onset group had more cases of gestational diabetes, whereas the early-onset group had a higher blood pressure, showed more proteinuria, had more liver and renal damage, exhibited more serious adverse maternal, fetal, and neonatal outcomes, was more likely to be admitted to the intensive care unit, and required longer hospital stays (all P < 0.05). In addition, the early-onset group had fewer prenatal care appointments and was more often transferred from a primary or secondary care hospital. The logistic regression analysis showed that a weekly weight gain of > 100 g was a risk factor for ESPE and that fewer prenatal care appointments were a risk factor for ESPE in pregnant women with female fetuses. Moreover, logistic regression analysis indicated that nulliparity and gestational diabetes during the current pregnancy were risk factors for LSPE. In conclusion, compared with the women with LSPE, those with ESPE usually had worse maternal, fetal, and neonatal outcomes. More frequent prenatal screening and care should be provided for pregnant women with high-risk factors.

The implementation of non-invasive PGT-A offers a new strategy to genetically assess the preimplantation embryo and to enhance IVF results. The extraction of DNA from the embryo culture medium has been sufficiently demonstrated, and the ability to obtain chromosomal information as a result is particularly interesting. As morphological criteria have proven to have a weak correlation with embryo ploidy status, this technique emerges as a promising alternative for embryo selection. It also appears reasonable that avoiding biopsy may enhance further embryo development. However, there are growing concerns regarding several aspects of this technique, such as the origin of this cell free DNA, the degree of representativeness of the whole embryo, the need for extended culture or the absence of standardized protocols. Despite the published data on good prognosis couples are promising, niPGT-A is yet to be considered a substitute for trophectoderm biopsy. The current SWOT analysis aims to summarize both resolved and unresolved issues, as well as limiting aspects of niPGT-A.

The menstrual cycle is an intricate biological process governed by hormonal changes that affect different facets of a woman's reproductive system. This review provides an overview of neurotransmitter alterations during different menstrual cycle phases and their effects on physiology and psychology. During the follicular phase, rising estrogen levels increase serotonin synthesis, enhancing mood, cognition, and pain tolerance. Estrogen may also influence dopamine levels, promoting motivation and reward sensitivity. GABA, involved in anxiety regulation, may be modulated by estrogen, inducing relaxation. Ovulation involves fluctuating dopamine and serotonin levels, potentially affecting motivation and positive mood. In the luteal phase, rising estrogen and progesterone may reduce serotonin availability, contributing to mood dysregulation, while enhanced GABAergic neurotransmission promotes sedation. Menstruation is characterized by declining estrogen and progesterone, potentially leading to mood disturbances, fluctuating GABAergic and dopaminergic neurotransmitter systems, relaxation, fatigue, motivation, and pleasure variations. Understanding neurotransmitter alterations during the menstrual cycle unveils the neurobiological mechanisms behind menstrual-related symptoms and disorders, facilitating targeted interventions. Pharmacological approaches targeting neurotransmitter systems, nutritional interventions, and lifestyle modifications show promise in managing menstrual symptoms. Future research should focus on further understanding neurotransmitter dynamics, personalized medicine, unexplored neurotransmitter roles, and integrating psychosocial factors. This knowledge will enhance well-being and quality of life for individuals experiencing menstrual-related challenges.

Endometrial elasticity is a potential new marker for assessing endometrial receptivity and pregnancy outcomes based on endometrial thickness and type. Currently, little research has been conducted on the elasticity of the endometrium using shear wave elasticity imaging (SWEI). This study aimed to explore whether endometrial elasticity is an ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer. A total of 245 infertile women underwent ultrasonography before embryo transfer at the Peking University Third Hospital. We compared the endometrial elasticity and sub-endometrial blood flow rate using SWEI in the groups with different pregnancy outcomes. Trends in clinical pregnancy outcomes across the quartiles of endometrial elasticity in the fundus of the uterus (E1) were assessed. Logistic regression analysis was performed to obtain odds ratios for clinical pregnancy outcomes based on the quartiles of E1, with or without adjusting for potential confounding variables. Women in the clinical pregnancy group had higher E1 values and sub-endometrial blood flow rates in the uterine fundus than those in the non-pregnancy group. Women in the highest quartile of E1 had the most favorable clinical pregnancy rates. Endometrial elasticity measured using SWEI is a promising ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer.

The decline in sperm parameters among obese males has attracted significant scholarly interest. The intestinal microbiota plays a crucial role in obesity, and investigating the intestinal-reproductive axis may offer a novel molecular approach to addressing the decline in male sperm parameters caused by obesity. To clarify whether probiotics, either alone or in conjunction with metformin, can enhance sperm parameters in obese male mice and assess the underlying mechanisms involved. 6-week-old male mice were constructed as obese models. Probiotics and metformin were used as intervention conditions. Changes in inflammatory factors and ROS content were detected by ELISA, morphological changes in testicular and colon tissues were observed by H&E staining, changes in intestinal microbiota abundance were detected by 16SrRNA gene sequencing, and changes in metabolites such as blood glucose, blood lipids, and lipopolysaccharide were detected by biochemical testing to investigate the mechanism of probiotics, metformin, and their combination to ameliorate reproductive impairment in obese male mice. Our results revealed that high-fat diet would result in reduced testicular spermatogenic tubule hierarchy, decreased spermatogenic cell counts, decreased sperm concentration and motility, and altered abundance of intestinal microbiota, whereas the combination of probiotics and metformin could restore high-fat-mediated pathophysiological alterations thereby ameliorating spermatogenic disorders in mice. The combination of probiotics and metformin can attenuate inflammation and oxidative stress, while enhancing androgen production to improve testicular spermatogenic function by re-construction intestinal microbiota equilibrium in HFD mice.