Reproduction & fertility最新文献

Abstract: The objective of the study was to i) characterize the aerobic and microaerophilic vaginal microbiota of collared peccaries (Pecari tajacu) across reproductive stages and ii) correlate microbiota findings with progesterone levels and vaginal cytology at each reproductive stage. Samples were collected for progesterone assessment (serum concentration), vaginal cytology, and microbial analysis (after isolation followed by MALDI-TOF identification) from four young pubescent, four non-pregnant, and three pregnant females. Microbial composition varied according to the reproductive stage: young pubescent females predominantly harbored Alcaligenes faecalis (Proteobacteria; 33.3%), non-pregnant females primarily hosted Bacillus badius and Staphylococcus microti (Firmicutes; 85.7%), and pregnant females had more Bacillus cereus and Mammaliicoccus sciuri (Firmicutes; 54.5%). No significant correlation (P > 0.05) was found between microbial proportions and progesterone levels or vaginal cytology. Although no differences were detected in the proportions of different vaginal bacterial populations, there was great qualitative diversity of species of microorganisms among females at different reproductive stages. While the small sample size may have limited our ability to detect more subtle quantitative differences, these findings provide foundational insights into the reproductive microbiota of collared peccaries, with potential implications for their conservation and management.

Lay summary: Despite the importance of reproductive microbiomes in animal conservation, there is still a lack of knowledge in many wild species. The present study characterized for the first time the composition of the aerobic and microaerophilic microbiota (bacteria that can survive in the presence of oxygen or in low-oxygen conditions, respectively) of the vaginal tract from collared peccaries (pig-like mammals from Central and South America commonly known as musk hogs) at different reproductive stages. Although no differences were detected in the proportions of different vaginal bacterial populations, there was great qualitative diversity of species of microorganisms among females at different reproductive stages. These findings provide foundational insights into the reproductive microbiota of collared peccaries, with potential implications for their conservation and management.

Abstract: Uterine rupture is a major complication of caesarean section (CS) associated with high fetal and maternal morbidity. The objective is to develop an in vivo model of uterine healing and rupture after CS in order to analyse histological phenomena controlling scarring tissue development and potential causes of defects. Eighteen pregnant primiparous female rabbits were bred naturally. At caesarean, after 28 days of gestation, foetuses were either extracted through a longitudinal incision in one of the uterine horns ('CS horn') or via a short incision at the tip of the contralateral horn ('control horn'). The uterine horns were sutured in a single layer, all by the same surgeon. They were mated again 14 days later and euthanised at G28. Genital tracts were collected for histological, biomechanical and polarimetric analyses. Macroscopically, 2/18 presented a dehiscence and 1/18 a spontaneous rupture. The mean thickness of the scarred area was significantly lower, 0.9 mm (0.7-1.4), than the non-scarred area on CS horns 2.2 (1.6-2.3) or control horns 2 (1.5-2.3) (P < 0.0001). The scar zone was statistically more fibrous (P < 0.0001), containing fewer vessels (P = 0.03), oestrogen receptors (P < 0.001) and progesterone receptors (P < 0.0001). After balloon inflation, rupture occurred in the scar zone in 8 out of 17 cases (47%). Polarimetry revealed that the scar zone was statistically inhomogeneous (73%). Multifactorial analysis identified groups with poor uterine healing and less resistance to rupture (balloon inflation), mostly in cases of thin myometrium in the scar, and a group with strong resistance to rupture and correct healing characteristics.

Lay summary: CS rates are rising across the world. When a CS is carried out, it can lead to scarring on the uterus that can affect its resistance to pressure. During the next pregnancy, the uterus can tear, increasing risks to the mother and baby. We carried out CSs in rabbits, allowing us to analyse the scar on the uterus, the healing and tissue resistance. The scarred part of the uterus was statistically thinner, more fibrous and contained fewer vessels and hormone receptors than the area without scarring. Under similar conditions, poor healing was observed in some animals, reducing resistance in following pregnancies. These results suggest that individual and genetic factors have an effect on healing after a CS. This study may improve our knowledge and management of care for patients who have a CS in order to reduce complications.

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Abstract: Intending parents on the African continent have limited access to quality services for infertility treatment. South Africa is the primary provider of fertility care on the continent, but because specialist training is only available in three public (teaching) hospitals, supported through partnerships with private institutions, there is a shortage of medical staff and waiting times for admission to training programmes can be years. We draw on data from our qualitative research study on assisted reproduction, generated from clinic visits, informal interviews, participation in science meetings, and formal interviews with 117 patients, gamete donors, clinicians, reproductive scientists and others to explore access to and motivation for training. Trainees' reasons for embarking on this specialisation included: concern with limited access to gynaecological and fertility care on the continent; lack of skilled fertility specialists and embryologists; and lack of options for assisted reproduction available to low-income intending parents. Trainee fellows expressed commitment to low-cost IVF models to address the lack of affordable and accessible reproductive health care. Fertility specialists often shared this concern and emphasised the need for trained professionals to expand services. In general, interviewees felt that infertility care and assisted reproduction were regarded as of lesser importance to other reproductive and health problems, despite the extent of infertility and the demand for assisted reproduction technology (ART) on the continent.

Lay summary: Countries across the African continent have the highest infertility rate in the world, yet access to diagnosis of cause, treatment and assisted reproductive technology is sparse. Assisted reproduction clinics now operate in several countries, particularly Ghana, Nigeria, Kenya and South Africa. Most support is in the private health system, and few women and men have access to low-cost assisted reproduction services at public hospitals. While clinics, biobanking services and laboratories are sparse, so too is training. We draw on data from a large study on assisted reproduction in South Africa to explore the provision of training. Most training is provided in South Africa, and people from other countries can access this. However, few teaching hospitals provide training, and people face long delays, sometimes years, before they can enrol. The limited opportunities for training seriously impact the capacity of countries to meet the health needs and support the reproductive hopes of many of their populations.

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Abstract: Delayed fecundability, defined as trying to conceive for ≥12 months without success, is a growing global concern due to the threat of fertility rates falling below the replacement level. This study aimed to predict delayed fecundability and identify influential predictors. Secondary data from recent Performance Monitoring for Action (PMA) surveys on fertility, contraception, and reproductive health in five sub-Saharan African countries were used. Preprocessing and feature engineering included imputation, encoding, and correlation filtering. Feature selection was done using the Boruta algorithm. Machine learning models, including random forest, XGBoost, and LightGBM, were developed and optimized via grid search with cross-validation. Models were compared using default hyperparameters. Interpretability was enhanced through SHapley Additive exPlanations (SHAP) plots, and heterogeneity was explored with subgroup SHAP analysis to identify context-specific predictor effects. Delayed fecundability was present in 31.01% of women. Grid search optimization improved model performance, with random forest achieving the highest accuracy (79.2%) and AUC (0.94). SHAP analysis identified key predictors, including age 36-49 (0.211), being married (0.208), ovulation-inducing treatment (0.173), and herbal remedy use (0.118). Subgroup SHAP analysis revealed heterogeneity: younger age reduced risk in 15-25-year-olds, fertility treatment history was the main risk driver in treated women, and marital status and childbirth had variable effects across subgroups. The random forest model best predicted delayed fecundability, with age, marital status, and treatment history as key predictors. Subgroup SHAP analysis revealed risk patterns across populations. Targeted screening and tailored fertility counseling, especially for couples with prior fertility treatments, are recommended to support timely conception.

Lay summary: Many women struggle to get pregnant even after trying for a year or more, a condition called delayed fecundability. This issue is becoming more common worldwide and can signal problems with fertility. We used data from surveys in five African countries to find out which factors may predict this delay. Using computer models that can learn from data, we found that age, marital status, and past use of fertility treatments were strong predictors. Our best model correctly identified nearly 80% of women with delayed fecundability. To make the findings easy to understand, we used a method that explains how each factor influences the result. We also found that the effects of these factors vary by age and treatment history. Our results can help health workers identify women at higher risk earlier, especially in places where fertility services are limited, and provide them with better, more personalized care.

Our primary aim was to investigate the reversibility of the negative impact of smoking on male fertility. Secondarily, we studied the effect of both time after smoking cessation as well as the smoking index on semen quality improvement. Our study included 60 participants who applied to a smoking cessation program. The volunteers started by completing a fertility background questionnaire. Two semen specimens, provided two weeks apart, were analyzed according to the WHO guidelines for each candidate on three different occasions. The first was right before smoking cessation followed by the 2nd and 3rd at three and six months after stopping smoking. Semen quality was compared between the three occasions. The degree of change was correlated with the level of smoking. The nicotine level in urine was used for smoking cessation compliance monitoring during the study. Comparing semen quality on the 3 different occasions respectively, we detected a significant improvement in semen volume (3.33 ml ± 1.07 vs. 3.88 ml ± 0.80 vs. 4.34 ml ± 0.67, P < 0.001), sperm concentration (14.77 million /ml ± 6.49 vs. 17.71 million/ml ± 6.41 vs. 19.27 million/ml ± 6.46, P < 0.001), total sperm count (49.33 million ± 25.31 vs. 70.16 million ± 30.85 vs. 84.01 million ± 31.00, P < 0.001), progressive motility (20.7% vs. 35.3% vs. 42.28%, P < 0.001), total motility (41.48% vs. 60.33% vs. 67.67%, P < 0.001) and abnormal morphology (69.32% Vs. 50.88% vs. 40.82%, P < 0.001). Improvement in all parameters was positively correlated to time after cessation. Higher smoking indices were related to higher levels of improvement in semen volume, sperm concentration, and total count (areas under the curve of 0.867, 0.852, and 0.863 respectively, P < 0.001 for each). Our conclusion was that the negative effect of smoking on semen quality is reversible. Smoking cessation has a time-dependent positive effect on main semen parameters, hence, positive potential for fecundity improvement in men. Extensive research efforts have always focused on the negative effects of smoking on male reproduction by comparing fertility in smokers versus non-smokers. There are very few studies looking at the effect of smoking cessation on male fertility. Our primary aim was to investigate the whether the negative impact of smoking on male fertility was reversible. Our study included 60 participants who applied to a smoking cessation program. The volunteers started by completing a fertility background questionnaire. Each candidate provided two semen specimens two weeks apart, on three occasions. The first was right before smoking cessation followed by the 2nd and 3rd at three and six months after stopping smoking. Semen quality was compared between three occasions. The degree of change was correlated with smoking levels. We found the negative effects of smoking on semen is reversible.

Abstract: Chronic endometritis, defined by chronic inflammation of the endometrium, remains a clinical and biologic challenge even using hysteroscopy allowing a direct vision of the uterine cavity without anesthesia, and conventional histology using Hematoxylin and Eosin staining. Our primary objectives were to evaluate the relevance of hysteroscopy and conventional histology compared to immunohistochemical expression of syndecan-1 (CD138, a marker of plasma cells), which is a heparan sulfate proteoglycan involved in inflammation and enables diagnosis of chronic endometritis. The second objective was to evaluate the impact of antibiotics on pregnancy rate. A retrospective study was conducted involving infertile women undergoing hysteroscopy and endometrial biopsy. Chronic endometritis was assessed using hysteroscopic findings and conventional histology compared to CD138 immunostaining. Effects of antibiotic therapy on CD138 expression on a second biopsy and on pregnancy rate were evaluated. Among the 661 infertile patients, 51 underwent hysteroscopy and endometrial biopsy. Twenty-three had a normal uterine cavity (45%) and among 28 patients with abnormal uterine cavity, ten (35.7%) had hysteroscopic findings of chronic endometritis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the hysteroscopy were 22, 100, 100, and 17%, with an infinite OR and an accuracy of 68.6, and 61.4, 100, 100%, 2.9%, and 66.7% respectively for conventional histology. The correlation coefficient between the first and second reading following CD138 immunostaining was moderate (Cohen's Kappa: 0.44 (95% CI: -0.059; 0.767) but good for plasma cell quantification (intraclass correlation coefficient 0.948). Plasma cell count was not predictive of pregnancy rate (P = 0.65) with an OR of 1.00. Pregnancy rate was significantly higher in treated patients (53%, 10/19) than in untreated patients (20%, 5/25) with an OR of 4.4 (95% CI: 1.17-16.8; P = 0.03).

Summary: Chronic endometritis is a reversible cause of infertility and remains a clinical and biologic challenge even using hysteroscopy and conventional histology and relies on the presence of plasma cells in immunohistochemistry. Our results underline the low accuracy of hysteroscopy and conventional histology to assess chronic endometritis, thus supporting the systematic use of CD138 immunostaining in infertile women even in the case of normal endometrium. Moreover, pregnancy rate seems enhanced by antibiotic therapy.

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Lay summary: Creatine is a nutrient that helps provide energy to different parts of the body, including the testes. Since making sperm takes a lot of energy, creatine might play a role in supporting sperm health. Some studies suggest it could help, while others raise concerns. However, it is still unclear what effect, if any, creatine from food has on sperm. To learn more, we looked at data from over 1,300 males in the US, aged 12 and older. We compared how much creatine they got from their diet with levels of two hormones in the blood that are related to sperm production. We found no strong link between dietary creatine and these hormone levels. This suggests that creatine from food probably does not have a major effect - good or bad - on male reproductive health. Since this study used existing data and did not test creatine directly in an experiment, we cannot say for sure if creatine causes any changes. More research, especially studies that look directly at sperm, is needed to better understand how creatine might affect fertility.

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Abstract: Current treatments for endometriosis are unsuitable for women who wish to conceive. To verify the supposed beneficial effects of Graptophyllum pictum (G. pictum) on reproductive diseases and inflammation, endometriosis was induced in female Wistar rats using a slightly modified protocol. After verification of successful transplantation (42 days), the animals were co-treated for 7 days with estradiol valerate (E2V; 0.5 mg/kg and the aqueous (GPC) or methanolic (GPM) extracts of G. pictum at doses of 50 and 275 mg/kg. Positive controls received aspirin (3 mg/kg) or letrozole (10 mg/kg). Normal and negative controls received vehicle (distilled water, 10 mL/kg). On day 7, animals were injected with oxytocin 30 min before sacrifice to evaluate some dysmenorrhea-like model parameters. Five animals per group were then sacrificed, and the remaining five animals were mated with males of proven fertility for 25 days. G. pictum extracts at all doses significantly (P < 0.001) increased the time of writhing latency and decreased its frequency and the volume of implant (P < 0.05) at the GPM 50 mg/kg dose. Levels of interleukin-6, tumor necrosis factor-alpha, and vascular angiogenic growth factor were reduced (P < 0.001) with all treatments. They also increased (P < 0.05) the serum superoxide dismutase and glutathione levels and decreased serum nitrite and malondialdehyde levels. In addition, the number of Graafian follicles (P < 0.05), fertility, and pregnancy rates were increased with the treatments. G. pictum extracts showed anti-inflammatory, antioxidant, and fertilizing effects in Wistar rats with endometriosis.

Lay summary: Asymptomatic in some individuals, endometriosis is an estrogen-dependent disease that causes infertility and severe pelvic pain, especially during menstrual periods and sexual intercourse. Higher cesarean rates worldwide have led to more cases of endometriosis (scar endometriosis). The delay of diagnosis (between 2 and 13 years) leads to increased misdiagnosis among patients and healthcare costs. There is no cure, but current treatments aim to alleviate spasms and pain by inhibiting estrogen production, and they are therefore unsuitable for women wishing to conceive, since they affect ovulation. Hence, there is a need to seek medical treatments that do not prevent pregnancy. Apart from its ornamental worth, Graptophyllum pictum, also called caricature plant, is traditionally used to relieve pain and treat reproductive disorders. After abdominal auto-transplantation of uterine fragments in rats, water-based and alcohol-based extracts of G. pictum promoted fertility by improving menstrual pain, egg development, and reducing cell damage and inflammation, which contribute to the progression of endometriosis.

Abstract: Filamin A (FLNA) regulates the mechanical properties and shape of cells by cross-linking actin filaments orthogonally. It also serves as a scaffold for numerous interacting proteins, thereby coordinating cell differentiation and morphogenesis. The role of FLNA in the human ovary is unknown. Immunohistochemistry indicated its expression in granulosa cells (GC) and oocytes in human and nonhuman primate ovaries. Studies in cultured human GC and KGN granulosa tumor cells showed that FLNA colocalizes with actin filaments, as expected. Forskolin decreased FLNA transcript and protein levels and caused a loss of filamentous FLNA and actin staining. In GC, this was accompanied by a pronounced change in cell shape and a massive increase in steroidogenic enzyme transcript levels. Further putative interaction partners of FLNA were identified upon immunoprecipitation followed by mass spectrometry. Cytoskeleton-associated proteins (e.g. FLNB and plectin), but also unexpected proteins (e.g. major vault protein and mitochondrial stress-70 protein), were found in both cellular models, while, e.g. cholesterol monooxygenase and gap junction α-1 were exclusively enriched in GC. Immunofluorescence revealed that plectin, one of the interaction partners identified in KGN cells, colocalized with FLNA. A siRNA-mediated knockdown of FLNA in KGN cells led to an increase in cell size, supporting a role in the regulation of the cytoskeleton. These studies demonstrate the widespread expression of FLNA in human ovarian cells in situ, provide insight into its regulation, and identify its potential interaction partners. Our data indicate that FLNA has specific roles in GC in regulating cytoskeletal activities, including cell size and steroidogenic competence.

Lay summary: The ovary produces hormones and egg cells. Eggs are enclosed in cellular spheres, called follicles, and are nursed by the granulosa cells (GC). Follicles increase in size and then acquire the ability to produce hormones. How this is regulated in an orderly way in women is not fully known. It involves the interaction of many players. We describe an as yet unknown player, filamin A. While many roles for filamin A have been described in other organs, such roles in the ovary were unknown. We therefore studied isolated human GC and granulosa tumor cells. We examined how filamin A is regulated and found that filamin A has specific roles in GC maturation and initiation of their hormone-producing function.