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Biomolecules
Special Issues
Molecular Aspects of Female Infertility
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Molecular Aspects of Female Infertility

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 4600

Special Issue Editor

Dr. Mara Marongiu

E-Mail Website
Guest Editor
The National Research Council (CNR), Institute for Genetic and Biomedical Research (IRGB), Lanusei, OG, Italy
Interests: genetics; infertility; rare diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to the Special Issue entitled “Molecular Aspects of Female Infertility.”

Female infertility represents a growing health problem, especially in industrialized countries, where the ongoing trend of delaying pregnancy beyond the age of 35 results in a significant reduction in fertility rates. Worldwide, infertility affects between 8 and 12% of reproductive-aged couples. Hormone conditions, medical conditions, age, lifestyle, and environmental factors can be predisposing factors for infertility in women.

The comprehension of the molecular mechanisms and genetic factors underlying female infertility, including reproductive aging and menopause, is fundamental to finding ways to preserve fertility and protect women from menopause-related pathologies.

With this research topic, we aim to provide an overview of the genetic and molecular causes of female infertility and highlight the molecular mechanisms underlying ovarian function, infertility, and reproductive aging. This would help to identify therapeutic approaches to preserve female fertility by providing potential targets of intervention (e.g., genes/proteins/molecules) that could be exploited for clinical use.

To achieve this, authors are invited to submit original research articles and reviews covering the following topics:

- Genetic mechanisms leading to ovarian aging and female infertility.
- Molecular mechanisms, genetic factors, and pathways regulating ovarian development, function, and aging.
- Female infertility rates worldwide and how they are affected by genetic factors and lifestyle.

Dr. Mara Marongiu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • female infertility
  • reproduction
  • ovary
  • reproductive aging
  • genetic disorders

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Published Papers (3 papers)

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Research

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21 pages, 25152 KiB  
Article
Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis
by Siyu Lin, Yushan Li, Wei Liu, Yanzhi Du and Tao Tao
Biomolecules 2025, 15(4), 572; https://doi.org/10.3390/biom15040572 - 12 Apr 2025
Viewed by 476
Abstract
Background: Polycystic ovary syndrome (PCOS) is a leading cause of infertility but also a metabolic disorder, frequently associated with obesity, insulin resistance, and diabetes. However, its etiology remains inadequately understood. Recent studies have increasingly implicated neutrophil extracellular traps (NETs) in the pathogenesis of [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is a leading cause of infertility but also a metabolic disorder, frequently associated with obesity, insulin resistance, and diabetes. However, its etiology remains inadequately understood. Recent studies have increasingly implicated neutrophil extracellular traps (NETs) in the pathogenesis of metabolic diseases. Methods: Serum and follicular fluid samples were collected from patients with PCOS and control populations to assess NETs levels. The effects of NETs were investigated using DNase I to reduce NETs in dehydroepiandrosterone sulfate (DHEAS)-induced PCOS rats. Metabolic differences were further analyzed by untargeted metabolomics, and in vitro studies were conducted using primary bone marrow-derived neutrophils and normal mouse liver cell lines. Results: Markers of NETs in both the serum and follicular fluid of patients with PCOS were significantly higher than those in the control group. PCOS rats treated with DNase I exhibited significant improvements in glucose metabolism. Untargeted metabolomics analysis of liver tissue from these rats revealed alterations in the glycolysis pathway. Subsequent in vitro experiments demonstrated that treatment with NETs-conditioned medium (NETs CM) led to reduced insulin sensitivity, glucose uptake, and glucose utilization in liver cells, accompanied by varying degrees of decline in the transcription, translation, and function of glycolysis pathway proteins. Conclusions: NETs may be involved in the regulation of insulin resistance pathogenesis in PCOS by downregulating glycolytic pathways in the liver. Our study offers a novel strategy for insulin resistance intervention in PCOS. Full article
(This article belongs to the Special Issue Molecular Aspects of Female Infertility)
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10 pages, 1292 KiB  
Article
Endometrial Dysbiosis: A Possible Association with Estrobolome Alteration
by Giorgia Scarfò, Simona Daniele, Elisa Chelucci, Francesca Papini, Francesco Epifani, Maria Ruggiero, Vito Cela, Ferdinando Franzoni and Paolo Giovanni Artini
Biomolecules 2024, 14(10), 1325; https://doi.org/10.3390/biom14101325 - 18 Oct 2024
Cited by 2 | Viewed by 1353
Abstract
Background/Objectives: Microbiota modification at the endometrial level can favor gynecological diseases and impair women’s fertility. The overgrowth of pathogen microorganisms is related to the contemporary alteration of estrogen-metabolizing bacteria, including β-glucuronidase, thereby enhancing estrogen-related inflammatory states and decreasing anti-inflammatory cells. The possible connection [...] Read more.
Background/Objectives: Microbiota modification at the endometrial level can favor gynecological diseases and impair women’s fertility. The overgrowth of pathogen microorganisms is related to the contemporary alteration of estrogen-metabolizing bacteria, including β-glucuronidase, thereby enhancing estrogen-related inflammatory states and decreasing anti-inflammatory cells. The possible connection between estrobolome impairment and gynecological diseases has been suggested in animal models. Nevertheless, in humans, coherent evidence on the estrobolome alteration and functionality of the female reproductive tract is still lacking. The objective of this study was to explore alterations in estrogen-related signaling and the putative link with endometrial dysbiosis. Methods: Women with infertility and repeated implantation failure (RIF, N = 40) were enrolled in order to explore the putative link between estrogen metabolism and endometrial dysbiosis. Endometrial biopsies were used to measure inflammatory and growth factor molecules. β-glucuronidase enzyme activity and estrogen receptor (ER) expression were also assessed. Results: Herein, increased levels of inflammatory molecules (i.e., IL-1β and HIF-1α) and decreased levels of the growth factor IGF-1 were found in the endometrial biopsies of patients presenting dysbiosis compared to eubiotic ones. β-glucuronidase activity and the expression of ERβ were significantly enhanced in patients in the dysbiosis group. Interestingly, Lactobacilli abundance was inversely related to β-glucuronidase activity and to ERβ expression, thus suggesting that an alteration of the estrogen-activating enzyme may affect the expression of ERs as well. Conclusions. Overall, these preliminary data suggested a link between endometrial dysbiosis and estrobolome impairment as possible synergistic contributing factors to women infertility and RIF. Full article
(This article belongs to the Special Issue Molecular Aspects of Female Infertility)
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Review

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21 pages, 4092 KiB  
Review
Irisin in Reproduction: Its Roles and Therapeutic Potential in Male and Female Fertility Disorders
by Muhammad Ibrahim Khan, Muhammad Imran Khan and Fazal Wahab
Biomolecules 2024, 14(10), 1222; https://doi.org/10.3390/biom14101222 - 27 Sep 2024
Viewed by 2096
Abstract
The current study focused on identifying the potential of irisin in mammalian reproduction. The established role of irisin, a proteolytic product of FNDC5, in adipose tissue browning, energy metabolism, and thermogenesis suggests its role in reproductive health, often disturbed by metabolic imbalances. Various [...] Read more.
The current study focused on identifying the potential of irisin in mammalian reproduction. The established role of irisin, a proteolytic product of FNDC5, in adipose tissue browning, energy metabolism, and thermogenesis suggests its role in reproductive health, often disturbed by metabolic imbalances. Various studies on mice demonstrated irisin′s role in improving spermatogenesis, sperm count, and testosterone levels by influencing the hypothalamus–pituitary–gonadal axis. Moreover, in females, there is a fluctuation in levels of irisin during critical reproductive stages, including menstrual cycles, puberty, and pregnancy. Conditions like pregnancy complications, precocious puberty, and polycystic ovary syndrome (PCOS) are found to have an association with abnormal irisin levels. The potential role of irisin in endometrial receptivity and preventing endometritis is also discussed in this review. Overall, the influence of irisin on female and male reproduction is evident from various studies. However, further research is needed to elucidate irisin mechanism in reproduction and its potential as a therapeutic or diagnostic tool for reproductive dysfunctions and infertility. Full article
(This article belongs to the Special Issue Molecular Aspects of Female Infertility)
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