Nutrients

Editorial

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Open AccessEditorial

Impact of Nutrition on Female Reproductive Disorders

by Pasquapina Ciarmela and Stefania Greco

Nutrients 2023, 15(21), 4576; https://doi.org/10.3390/nu15214576 - 27 Oct 2023

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Abstract

The female reproductive system is a delicate and complex system in the body that can be affected by many disorders [...] Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

Research

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11 pages, 434 KiB

Open AccessArticle

Prevalence of Vitamin D Insufficiency and Its Determinants among Women Undergoing In Vitro Fertilization Treatment for Infertility in Sweden

by Paulina Maaherra Armstrong, Hanna Augustin, Linnea Bärebring, Amra Osmancevic, Maria Bullarbo, Ann Thurin-Kjellberg and Panagiotis Tsiartas

Nutrients 2023, 15(12), 2820; https://doi.org/10.3390/nu15122820 - 20 Jun 2023

Cited by 3 | Viewed by 2575

Abstract

There is a lack of research on women with infertility in the northern latitudes, where vitamin D insufficiency is high. Therefore, this study aimed to assess the prevalence and determinants of vitamin D insufficiency (serum 25(OH)D concentration < 50 nmol/L) among women undergoing [...] Read more.

There is a lack of research on women with infertility in the northern latitudes, where vitamin D insufficiency is high. Therefore, this study aimed to assess the prevalence and determinants of vitamin D insufficiency (serum 25(OH)D concentration < 50 nmol/L) among women undergoing in vitro fertilization (IVF) treatment. Thus, 265 women scheduled for IVF/intracytoplasmic sperm injection (ICSI) between September 2020 and August 2021 at Sahlgrenska University Hospital in Gothenburg, Sweden, were included. Data on serum 25(OH)D concentration, vitamin D intake, and sun exposure were collected via questionnaires and blood samples. Approximately 27% of the women had 25(OH)D insufficiency, which was associated with longer infertility duration. The likelihood of insufficiency was higher among women from non-Nordic European countries (OR 2.92, 95% CI 1.03–8.26, adjusted p = 0.043), the Middle East (OR 9.90, 95% CI 3.32–29.41, adjusted p < 0.001), and Asia (OR 5.49, 95% CI 1.30–23.25, adjusted p = 0.020) than among women from Nordic countries. Women who did not use vitamin D supplements were more likely to have insufficiency compared with supplement users (OR 3.32, 95% CI 1.55–7.10, adjusted p = 0.002), and those who avoided sun exposure had higher odds of insufficiency compared to those who stayed “in the sun all the time” (OR 3.24, 95% CI 1.22–8.62, adjusted p = 0.018). Women with infertility in northern latitudes and those from non-Nordic countries who avoid sun exposure and do not take vitamin supplements have a higher prevalence of 25(OH)D insufficiency and longer infertility duration. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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13 pages, 1989 KiB

Open AccessArticle

The In Vitro Effects of Romina Strawberry Extract on 3D Uterine Leiomyosarcoma Cells

by Stefania Greco, Pamela Pellegrino, Francesca Giampieri, Franco Capocasa, Giovanni Delli Carpini, Maurizio Battino, Bruno Mezzetti, Stefano Raffaele Giannubilo, Andrea Ciavattini and Pasquapina Ciarmela

Nutrients 2023, 15(11), 2557; https://doi.org/10.3390/nu15112557 - 30 May 2023

Cited by 3 | Viewed by 1822

Abstract

Leiomyosarcoma is an aggressive soft tissue sarcoma derived from the smooth muscle cells of the uterus. We tested the effect of Romina strawberry extract treatment on three-dimensional cultured uterine leiomyosarcoma cells. We established 3D cultures in agarose gel, where the cells seeded were [...] Read more.

Leiomyosarcoma is an aggressive soft tissue sarcoma derived from the smooth muscle cells of the uterus. We tested the effect of Romina strawberry extract treatment on three-dimensional cultured uterine leiomyosarcoma cells. We established 3D cultures in agarose gel, where the cells seeded were able to form spheroids. We performed the observation and counting of the spheroids with a phase-contrast optical microscope, finding a decrease in the number of spheroids formed in the plates after 24 and 48 h treatment with 250 µg/mL of cultivar Romina strawberry extract. We also characterized the spheroids morphology by DNA binding fluorescent-stain observation, hematoxylin and eosin stain, and Masson’s trichrome stain. Finally, the real-time PCR showed a reduced expression of extracellular matrix genes after strawberry treatment. Overall, our data suggest that the fruit extract of this strawberry cultivar may be a useful therapeutic adjuvant for the management of uterine leiomyosarcoma. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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13 pages, 922 KiB

Open AccessArticle

Vitamin D Status in Women with a History of Infertility and Decreased Fecundability: A Population-Based Study

by Johanna Lumme, Laure Morin-Papunen, Paula Pesonen, Sylvain Sebert, Elina Hyppönen, Marjo-Riitta Järvelin, Karl-Heinz Herzig, Marja Ojaniemi and Maarit Niinimäki

Nutrients 2023, 15(11), 2522; https://doi.org/10.3390/nu15112522 - 29 May 2023

Cited by 5 | Viewed by 2342

Abstract

Background: Infertility and fecundability problems have been linked with lower 25-hydroxyvitamin D (25(OH)D) concentrations, but studies conducted with small, heterogenous or selected populations have shown inconsistent results. Methods: This study included women at age 31 from prospective population-based Northern Finland Birth Cohort 1966. [...] Read more.

Background: Infertility and fecundability problems have been linked with lower 25-hydroxyvitamin D (25(OH)D) concentrations, but studies conducted with small, heterogenous or selected populations have shown inconsistent results. Methods: This study included women at age 31 from prospective population-based Northern Finland Birth Cohort 1966. Serum 25(OH)D concentrations were evaluated between women with or without previous infertility examinations or treatments (infertility group, n = 375, reference group, n = 2051) and time to pregnancy (TTP) of over 12 months (decreased fecundability group, n = 338) with a wide range of confounders. Furthermore, 25(OH)D concentrations were also compared among reproductive outcomes. Results: The mean 25(OH)D concentration was lower and 25(OH)D < 30 nmol/L was more frequent in women with a history of infertility compared to reference group. Moreover, 25(OH)D > 75 nmol/L was more frequent in the reference group. The mean 25(OH)D concentration was lower in women who had had multiple miscarriages. Both history of infertility (β = −2.7, 95% confidence interval (CI) −4.6, −0.7) and decreased fecundability associated with lower 25(OH)D concentration (β = −4.1, 95% CI −7.4, −0.8) after adjustments. In conclusion, this population-based study demonstrated that previous infertility and decreased fecundability were associated with lower 25(OH)D. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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19 pages, 5117 KiB

Open AccessArticle

Colitis-Mediated Dysbiosis of the Intestinal Flora and Impaired Vitamin A Absorption Reduce Ovarian Function in Mice

by Ze Li, Chengzhen Chen, Wenjie Yu, Lingxia Xu, Haitao Jia, Chen Wang, Na Pei, Zibin Liu, Dan Luo, Jun Wang, Wenfa Lv, Bao Yuan, Jiabao Zhang and Hao Jiang

Nutrients 2023, 15(11), 2425; https://doi.org/10.3390/nu15112425 - 23 May 2023

Cited by 4 | Viewed by 2036

Abstract

Changes in the composition and ratio of the flora during colitis have been found to potentially affect ovarian function through nutrient absorption. However, the mechanisms have not been fully explored. To investigate whether colitis-induced dysbacteriosis of the intestinal flora affects ovarian function, mice [...] Read more.

Changes in the composition and ratio of the flora during colitis have been found to potentially affect ovarian function through nutrient absorption. However, the mechanisms have not been fully explored. To investigate whether colitis-induced dysbacteriosis of the intestinal flora affects ovarian function, mice were given dextran sodium sulfate (DSS) through drinking water. High-throughput sequencing technology was used to clarify the composition and proportion of bacterial flora as well as gene expression changes in the colon. Changes in follicle type, number, and hormone secretion in the ovary were detected. The results showed that 2.5% DSS could induce severe colitis symptoms, including increased inflammatory cell infiltration, severe damage to the crypt, and high expression of inflammatory factors. Moreover, vitamin A synthesis metabolism-related genes Rdh10, Aldh1a1, Cyp26a1, Cyp26b1, and Rarβ were significantly decreased, as well as the levels of the steroid hormone synthase-related proteins STAR and CYP11A1. The levels of estradiol, progesterone, and Anti-Mullerian hormone as well as the quality of oocytes decreased significantly. The significantly changed abundances of Alistipes, Helicobacter, Bacteroides, and some other flora had potentially important roles. DSS-induced colitis and impaired vitamin A absorption reduced ovarian function. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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12 pages, 1463 KiB

Open AccessArticle

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study

by Xinrui Yao, Sitong Dong, Wenzheng Guan, Lingjie Fu, Gaoyu Li, Zhen Wang, Jiao Jiao and Xiuxia Wang

Nutrients 2023, 15(9), 2143; https://doi.org/10.3390/nu15092143 - 29 Apr 2023

Cited by 2 | Viewed by 1786

Abstract

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective [...] Read more.

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045–1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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13 pages, 2400 KiB

Open AccessArticle

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

by Woojin Kang, Eri Ishida, Mitsuyoshi Amita, Kuniko Tatsumi, Hitomi Yonezawa, Miku Yohtsu, Daiki Katano, Kae Onozawa, Erika Kaneko, Wakako Iwasaki, Natsuko Naito, Mitsutoshi Yamada, Natsuko Kawano, Mami Miyado, Ban Sato, Hidekazu Saito, Takakazu Saito and Kenji Miyado

Nutrients 2022, 14(10), 2156; https://doi.org/10.3390/nu14102156 - 22 May 2022

Cited by 3 | Viewed by 4108

Abstract

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for [...] Read more.

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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Review

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13 pages, 495 KiB

Open AccessReview

Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth?

by Alice Guarano, Anna Capozzi, Martina Cristodoro, Nicoletta Di Simone and Stefano Lello

Nutrients 2023, 15(14), 3209; https://doi.org/10.3390/nu15143209 - 19 Jul 2023

Cited by 4 | Viewed by 6610

Abstract

Polycystic ovary syndrome (PCOS) is among the most common female endocrinopathies, affecting about 4–25% of women of reproductive age. Women affected by PCOS have an increased risk of developing metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and endometrial cancer. Given the pivotal [...] Read more.

Polycystic ovary syndrome (PCOS) is among the most common female endocrinopathies, affecting about 4–25% of women of reproductive age. Women affected by PCOS have an increased risk of developing metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and endometrial cancer. Given the pivotal role of insulin resistance (IR) in the pathogenesis of PCOS, in the last years, many insulin-sensitizing factors have been proposed for PCOS treatment. The first insulin sensitizer recommended by evidence-based guidelines for the assessment and treatment of PCOS was metformin, but the burden of side effects is responsible for treatment discontinuation in many patients. Inositols have insulin-mimetic properties and contribute to decreasing postprandial blood glucose, acting by different pathways. ALA is a natural amphipathic compound with a very strong anti-inflammatory and antioxidant effect and a very noteworthy role in the improvement of insulin metabolic pathway. Given the multiple effects of ALA, a therapeutic strategy based on the synergy between inositols and ALA has been recently proposed by many groups with the aim of improving insulin resistance, reducing androgen levels, and ameliorating reproductive outcomes in PCOS patients. The purpose of this study is to review the existing literature and to evaluate the existing data showing the efficacy and the limitation of a treatment strategy based on this promising molecule. ALA is a valid therapeutic strategy applicable in the treatment of PCOS patients: Its multiple actions, including antinflammatory, antioxidant, and insulin-sensitizing, may be of utmost importance in the treatment of a very complex syndrome. Specifically, the combination of MYO plus ALA creates a synergistic effect that improves insulin resistance in PCOS patients, especially in obese/overweight patients with T2DM familiarity. Moreover, ALA treatment also exerts beneficial effects on endocrine patterns, especially if combined with MYO, improving menstrual regularity and ovulation rhythm. The purpose of our study is to review the existing literature and to evaluate the data showing the efficacy and the limitations of a treatment strategy based on this promising molecule. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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24 pages, 1371 KiB

Open AccessFeature PaperReview

Melatonin in Endometriosis: Mechanistic Understanding and Clinical Insight

by Yiran Li, Sze-Wan Hung, Ruizhe Zhang, Gene Chi-Wai Man, Tao Zhang, Jacqueline Pui-Wah Chung, Lanlan Fang and Chi-Chiu Wang

Nutrients 2022, 14(19), 4087; https://doi.org/10.3390/nu14194087 - 1 Oct 2022

Cited by 8 | Viewed by 6261

Abstract

Endometriosis is defined as the development of endometrial glands and stroma outside the uterine cavity. Pathophysiology of this disease includes abnormal hormone profiles, cell survival, migration, invasion, angiogenesis, oxidative stress, immunology, and inflammation. Melatonin is a neuroendocrine hormone that is synthesized and released [...] Read more.

Endometriosis is defined as the development of endometrial glands and stroma outside the uterine cavity. Pathophysiology of this disease includes abnormal hormone profiles, cell survival, migration, invasion, angiogenesis, oxidative stress, immunology, and inflammation. Melatonin is a neuroendocrine hormone that is synthesized and released primarily at night from the mammalian pineal gland. Increasing evidence has revealed that melatonin can be synthesized and secreted from multiple extra-pineal tissues where it regulates immune response, inflammation, and angiogenesis locally. Melatonin receptors are expressed in the uterus, and the therapeutic effects of melatonin on endometriosis and other reproductive disorders have been reported. In this review, key information related to the metabolism of melatonin and its biological effects is summarized. Furthermore, the latest in vitro and in vivo findings are highlighted to evaluate the pleiotropic functions of melatonin, as well as to summarize its physiological and pathological effects and treatment potential in endometriosis. Moreover, the pharmacological and therapeutic benefits derived from the administration of exogenous melatonin on reproductive system-related disease are discussed to support the potential of melatonin supplements toward the development of endometriosis. More clinical trials are needed to confirm its therapeutic effects and safety. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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10 pages, 1807 KiB

Open AccessOpinion

Therapeutic Carbohydrate Restriction as a Metabolic Modality for the Prevention and Treatment of Abnormal Uterine Bleeding

by Andrea C. Salcedo, Jane Yun, Cody Carter and Elaine Hart

Nutrients 2023, 15(17), 3760; https://doi.org/10.3390/nu15173760 - 28 Aug 2023

Cited by 1 | Viewed by 8540

Abstract

Therapeutic carbohydrate restriction diets have been becoming increasingly popular over the years, resulting in dramatic weight loss and an improvement in metabolic disorders. Obesity, insulin resistance, and diabetes are the risk factors for many gynecologic morbidities such as uterine leiomyoma, endometrial polyps, and [...] Read more.

Therapeutic carbohydrate restriction diets have been becoming increasingly popular over the years, resulting in dramatic weight loss and an improvement in metabolic disorders. Obesity, insulin resistance, and diabetes are the risk factors for many gynecologic morbidities such as uterine leiomyoma, endometrial polyps, and polycystic ovarian syndrome. There is evidence suggesting that the pathogenesis of cardiovascular disease is similar to that seen in many causes of abnormal uterine bleeding. We aim to explain how cardiovascular disease risk factor reduction with the use of therapeutic carbohydrate restriction may prevent and potentially treat these gynecologic disorders. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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15 pages, 1926 KiB

Open AccessSystematic Review

Lower Fiber Consumption in Women with Polycystic Ovary Syndrome: A Meta-Analysis of Observational Studies

by Wing Ting Leung, Zhijing Tang, Yuanyuan Feng, Haiyun Guan, Zengshu Huang and Wei Zhang

Nutrients 2022, 14(24), 5285; https://doi.org/10.3390/nu14245285 - 12 Dec 2022

Cited by 4 | Viewed by 3548

Abstract

Polycystic ovary syndrome is a common endocrine disorder associated with metabolic abnormalities and gut microbiota dysbiosis. The deficiency of dietary fiber, a crucial nutrient in the daily diet, is also associated with a wide range of metabolic and reproductive abnormalities, as well as [...] Read more.

Polycystic ovary syndrome is a common endocrine disorder associated with metabolic abnormalities and gut microbiota dysbiosis. The deficiency of dietary fiber, a crucial nutrient in the daily diet, is also associated with a wide range of metabolic and reproductive abnormalities, as well as an altered gut microbial ecosystem. This study is a meta-analysis to summarize the available evidence on the dietary fiber intake level in PCOS patients. Databases of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched for observational studies, and 13 studies were finally included. The pooled standardized mean difference (SMD) with the 95% confidence interval (CI) of daily dietary fiber intake and total energy intake were calculated using the random-effects model. The pooled result (12 studies) on absolute dietary fiber intake showed that while there was no significant difference in the total energy intake [−0.17 (−0.44, 0.09), p = 0.208], the dietary fiber intake was significantly lower in PCOS women than those of controls [−0.32 (−0.50, −0.14), p < 0.001]. However, significant heterogeneity was detected across the studies (I² = 65.6%, p = 0.001). Meta-regression suggested that geographic region and dietary assessment method may confer borderline significance of influence on the heterogeneity. The pooled result (two studies) on dietary fiber intake which adjusted for total energy intake, however, showed no significant difference [−2.11 (−4.77, 0.56), p = 0.122]. In subgroup analyses based on absolute dietary fiber intake, a lower dietary fiber intake in PCOS was observed in studies conducted in Asia, adopted food diary or records or food recall as the dietary assessment method, had a case–control study design, or used Rotterdam criteria for PCOS diagnosis. The difference in SMD was still significant in the adult subgroup or in studies matched or unmatched for age. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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8 pages, 913 KiB

Open AccessCommentary

Relevance of Vitamin D and Its Deficiency for the Ovarian Follicle and the Oocyte: An Update

by Arkadiusz Grzeczka, Szymon Graczyk, Agnieszka Skowronska, Mariusz T. Skowronski and Paweł Kordowitzki

Nutrients 2022, 14(18), 3712; https://doi.org/10.3390/nu14183712 - 9 Sep 2022

Cited by 13 | Viewed by 2942

Abstract

For many years, vitamin D (VD) has been known to be an essential micronutrient with important relevance not only for the skeletal system, but also for numerous other mammalian organ systems. Low levels of VD result in a VD deficiency, which is a [...] Read more.

For many years, vitamin D (VD) has been known to be an essential micronutrient with important relevance not only for the skeletal system, but also for numerous other mammalian organ systems. Low levels of VD result in a VD deficiency, which is a global health problem. Moreover, VD deficiencies are linked to several pathologies, for instance, diseases of the cardiovascular system, diabetes mellitus, or sub- and infertility. In the past two decades, an increasing body of evidence has shown that adequate physiological levels of VD are crucial for the female gamete and its microenvironment, and VD deficiency has been associated with decreased live birth rates among women undergoing in vitro fertilization (IVF). With regard to the female reproductive tract, VD receptors (VDRs) have been detected in the ovary, endometrium, and the placenta. Although it has been reported that VD seems to be relevant for both calcium-dependent and independent pathways, its relevance for the oocyte’s developmental competence and life span remains elusive. Therefore, herein, we aim to provide an update on the importance of VD and VD deficiency for the oocyte and the follicular microenvironment. Full article

(This article belongs to the Special Issue Impact of Nutrition on Female Reproductive Disorders)

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