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Molecular Biology of Human Fertility—2nd Edition
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Molecular Biology of Human Fertility—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 11806

Special Issue Editors

Dr. Antonio Simone Laganà

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, 21100 Varese, VA, Italy
Interests: women’s health; minimally invasive procedures; up-to-date management; gynecology; reproductive health; surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Simone Garzon

E-Mail Website1 Website2
Guest Editor
Department of Surgery, Dentistry, Pediatrics, and Gynecology, AOUI Verona, University of Verona, 37126 Verona, Italy
Interests: infertility; fertility preservation; endometriosis; polycystic ovary syndrome; assisted reproduction technology; gynecologic surgical procedures; endometrial cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The inspiration behind this Special Issue titled "Molecular Biology of Human Fertility" stemmed from the desire to create a collection of manuscripts providing new evidence or summarizing the most recent available pieces of evidence on the molecular aspects of the complex mechanisms underlining human fertility. Live birth and before a clinical pregnancy result from a complex interaction of molecular pathways at the level of female and male gametes, their interaction during fecundation, and the development of the embryo before, during, and after implantation. All these mechanisms interact with the surrounding environment present at the level of gonads and male and female bodies, and later at the female genital tract level, from tubes to the endometrium and uterus. Knowledge of this molecular biology underlining human fertility is paramount to understand physiology and pathology, with the ultimate objective of successfully understanding and treating female and male infertility.

This Special Issue aims to publish groundbreaking research and review articles on basic and translational science (immunology, cell biology, genetics, and epigenetics) that may create new scenarios and change our perspective of the topic.

Dr. Antonio Simone Laganà
Dr. Simone Garzon
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • infertility
  • gametes
  • embryo
  • implantation
  • placenta
  • endometrium
  • gynecological endocrinology
  • assisted reproduction technology
  • ovaries
  • inflammation
  • endometriosis

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Published Papers (5 papers)

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Research

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14 pages, 1937 KiB  
Article
Transcriptomic Analysis Reveals Intrinsic Abnormalities in Endometrial Polyps
by Christine Shan-Chi Chiu, Ling-Yu Yeh, Szu-Hua Pan and Sheng-Hsiang Li
Int. J. Mol. Sci. 2024, 25(5), 2557; https://doi.org/10.3390/ijms25052557 - 22 Feb 2024
Cited by 1 | Viewed by 1664
Abstract
Endometrial polyps (EPs) are benign overgrowths of the endometrial tissue lining the uterus, often causing abnormal bleeding or infertility. This study analyzed gene expression differences between EPs and adjacent endometrial tissue to elucidate intrinsic abnormalities promoting pathological overgrowth. RNA sequencing of 12 pairs [...] Read more.
Endometrial polyps (EPs) are benign overgrowths of the endometrial tissue lining the uterus, often causing abnormal bleeding or infertility. This study analyzed gene expression differences between EPs and adjacent endometrial tissue to elucidate intrinsic abnormalities promoting pathological overgrowth. RNA sequencing of 12 pairs of EPs and the surrounding endometrial tissue from infertile women revealed 322 differentially expressed genes. Protein–protein interaction network analysis revealed significant alterations in specific signaling pathways, notably Wnt signaling and vascular smooth muscle regulation, suggesting these pathways play critical roles in the pathophysiology of EPs. Wnt-related genes DKK1 and DKKL1 were upregulated, while GPC3, GREM1, RSPO3, SFRP5, and WNT10B were downregulated. Relevant genes for vascular smooth muscle contraction were nearly all downregulated in EPs, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN. Overall, the results indicate fundamental gene expression changes promote EP formation through unrestrained growth signaling and vascular defects. The intrinsic signaling abnormalities likely contribute to clinical symptoms of abnormal uterine bleeding and infertility common in EP patients. This analysis provides molecular insights into abnormal endometrial overgrowth to guide improved diagnostic and therapeutic approaches for this troublesome women’s health condition. Confirmation of expanded cohorts and further investigations into implicated regulatory relationships are warranted. Full article
(This article belongs to the Special Issue Molecular Biology of Human Fertility—2nd Edition)
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11 pages, 4680 KiB  
Article
Human Sperm Head Vacuoles Are Related to Nuclear-Envelope Invaginations
by María José Gómez-Torres, Javier Luna-Romero, Pedro José Fernández-Colom, Jon Aizpurua, Manuel Avilés and Alejandro Romero
Int. J. Mol. Sci. 2023, 24(12), 10027; https://doi.org/10.3390/ijms241210027 - 12 Jun 2023
Cited by 3 | Viewed by 3059
Abstract
Nuclear vacuoles are specific structures present on the head of the human sperm of fertile and non-fertile men. Human sperm head vacuoles have been previously studied using motile sperm organelle morphology examination (MSOME) and their origin related to abnormal morphology, abnormal chromatin condensation [...] Read more.
Nuclear vacuoles are specific structures present on the head of the human sperm of fertile and non-fertile men. Human sperm head vacuoles have been previously studied using motile sperm organelle morphology examination (MSOME) and their origin related to abnormal morphology, abnormal chromatin condensation and DNA fragmentation. However, other studies argued that human sperm vacuoles are physiological structures and consequently, to date, the nature and origin of the nuclear vacuoles remains to be elucidated. Here, we aim to define the incidence, position, morphology and molecular content of the human sperm vacuoles using transmission electron microscopy (TEM) and immunocytochemistry techniques. The results showed that ~50% of the analyzed human sperm cells (n = 1908; 17 normozoospermic human donors) contained vacuoles mainly located (80%) in the tip head region. A significant positive correlation was found between the sperm vacuole and nucleus areas. Furthermore, it was confirmed that nuclear vacuoles were invaginations of the nuclear envelope from the perinuclear theca and containing cytoskeletal proteins and cytoplasmic enzyme, discarding a nuclear or acrosomal origin. According to our findings, these human sperm head vacuoles are cellular structures originating from nuclear invaginations and contain perinuclear theca (PT) components, allowing us to define a new term of ‘nuclear invaginations’ rather than ‘nuclear vacuoles’. Full article
(This article belongs to the Special Issue Molecular Biology of Human Fertility—2nd Edition)
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9 pages, 3816 KiB  
Communication
Isolation of Vaginal Epithelial Cells: In Preparation of Autologous Vaginal Tissue Lining for Congenital Absence of Vagina Patients
by Too Lih Yuan, Nadiah Sulaiman, Abdul Ghani Nur Azurah, Manira Maarof, Rabiatul Adawiyah Razali, Benson Koh, Roszita Ibrahim, Ani Amelia Zainuddin and Muhammad Dain Yazid
Int. J. Mol. Sci. 2023, 24(10), 8798; https://doi.org/10.3390/ijms24108798 - 15 May 2023
Viewed by 2140
Abstract
Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The [...] Read more.
Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility. Full article
(This article belongs to the Special Issue Molecular Biology of Human Fertility—2nd Edition)
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17 pages, 3419 KiB  
Article
Expression of Gal-9 on Dendritic Cells and Soluble Forms of TIM-3/Gal-9 in Patients Suffering from Endometriosis
by Dorota Suszczyk, Wiktoria Skiba, Anna Pawłowska, Grzegorz Polak, Rafał Tarkowski and Iwona Wertel
Int. J. Mol. Sci. 2023, 24(6), 5948; https://doi.org/10.3390/ijms24065948 - 21 Mar 2023
Cited by 4 | Viewed by 2167
Abstract
Immune system dysregulation is clinically evident in the pathogenesis of endometriosis (EMS). Changes in the dendritic cells (DCs) activity or phenotype may be involved in the implantation and growth of endometrial tissue outside the uterus in the disease. The TIM-3/Gal-9 axis is implicated [...] Read more.
Immune system dysregulation is clinically evident in the pathogenesis of endometriosis (EMS). Changes in the dendritic cells (DCs) activity or phenotype may be involved in the implantation and growth of endometrial tissue outside the uterus in the disease. The TIM-3/Gal-9 axis is implicated in the development of immune tolerance. However, the knowledge about the exact role of this pathway in the EMS is extremely poor. In the present study, we evaluated the expression of Gal-9 on myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the peripheral blood (PB) and peritoneal fluid (PF) of both EMS patients (n = 82) and healthy subjects (n = 10) via flow cytometry. We also investigated the concentrations of soluble Gal-9 and TIM-3 in the plasma and PF of EMS patients and the control group using ELISA. We showed significantly elevated percentages of mDCs-Gal-9+ and pDCs-Gal-9+, and significantly higher concentrations of the soluble form of Gal-9 and TIM-3 in the PF of EMS patients than in circulation. Our results led us to conclude that the accumulation of Gal-9 expressing mDCs and pDCs in the PF and high sTIM-3/Gal-9 production in the peritoneal cavity could represent the hallmark of immune regulation in EMS patients, which may augment the inflammatory process and development/maintenance of local immunosuppression. Full article
(This article belongs to the Special Issue Molecular Biology of Human Fertility—2nd Edition)
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Review

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15 pages, 935 KiB  
Review
The Molecular Link between Obesity and the Endometrial Environment: A Starting Point for Female Infertility
by Francesca Gonnella, Fani Konstantinidou, Marisa Donato, Daniela Maria Pia Gatta, Alessia Peserico, Barbara Barboni, Liborio Stuppia, Warren B. Nothnick and Valentina Gatta
Int. J. Mol. Sci. 2024, 25(13), 6855; https://doi.org/10.3390/ijms25136855 - 22 Jun 2024
Cited by 1 | Viewed by 1816
Abstract
Female infertility constitutes a growing health problem in developing countries and could be associated with several possible causes including reproductive disorders, congenital malformations, infections and hormonal dysfunction. Nonetheless, a series of additional factors can also negatively impact female fertility and are represented by [...] Read more.
Female infertility constitutes a growing health problem in developing countries and could be associated with several possible causes including reproductive disorders, congenital malformations, infections and hormonal dysfunction. Nonetheless, a series of additional factors can also negatively impact female fertility and are represented by chronic exposure to environmental pollutants, stress, unhealthy lifestyle choices such as cigarette smoking and, among others, obesity. Excess weight is associated with several chronic diseases, and growing evidence demonstrates that it can compromise reproductive physiology due to its influence on endometrial gene expression and receptivity. Thus, the current review of the literature mainly focused on how obesity can impair uterine receptivity, mostly from a molecular point of view throughout the window of implantation (WOI) period at an endometrial level. It was also highlighted that an obesity-related increase in adipose tissue may lead to a modulation in the expression of multiple pathways, which could cause a hostile endometrial environment with a consequent negative impact on the uterine receptivity and the establishment of pregnancy. Thanks to the use of the endometrial receptivity assay (ERA), a specific microarray that studies the expression of a series of genes, it is now possible to evaluate the endometrial status of patients with infertility problems in a more detailed manner. Moreover, female fertility and endometrial receptivity could be affected by endometriosis, a chronic benign gynecological disease, whose cause-and-effect relationship to obesity is still uncertain. Therefore, further investigations would be required to better elucidate these mechanisms that govern embryo implantation and could be potentially useful for the generation of new strategies to overcome implantation failure and improve the pregnancy rates in obese women. Full article
(This article belongs to the Special Issue Molecular Biology of Human Fertility—2nd Edition)
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