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International Journal of Molecular... Jan 2022Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive... (Review)
Review
Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.
Topics: Dysbiosis; Endometrium; Female; Fertilization; Humans; Microbiota; Pregnancy; Pregnancy Outcome; Virulence
PubMed: 35008911
DOI: 10.3390/ijms23010485 -
International Journal of Molecular... Jun 2023Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive... (Review)
Review
Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women.
Topics: Pregnancy; Female; Humans; Adult; Reproduction; Thyroid Hormones; Thyroid Diseases; Polycystic Ovary Syndrome
PubMed: 37372963
DOI: 10.3390/ijms24129815 -
The Indian Journal of Medical Research Dec 2019All individuals are exposed to certain chemical, physical, biological, environmental as well as occupational factors. The data pertaining to role of these factors on... (Review)
Review
All individuals are exposed to certain chemical, physical, biological, environmental as well as occupational factors. The data pertaining to role of these factors on female reproduction are scanty as compared to male. The available data suggest the adverse effects of certain toxicants, viz., metals such as lead, cadmium and mercury, pesticides such as bis(4-chlorophenyl)-1,1,1-trichloroethane and organic solvent such as benzene, toluene and ionizing radiation on the female reproductive system affecting directly the organ system or impacting in directly through hormonal impairments, molecular alterations, oxidative stress and DNA methylation impairing fertility as well as pregnancy and its outcomes. Thus, there is a need for awareness and prevention programme about the adverse effects of these factors and deterioration of female reproductive health, pregnancy outcome and offspring development as some of these chemicals might affect the developing foetus at very low doses by endocrine disruptive mechanism.
Topics: Benzene; DNA Methylation; Environmental Exposure; Female; Humans; Infertility, Male; Male; Metals; Occupational Exposure; Oxidative Stress; Pesticides; Pregnancy; Reproduction
PubMed: 32048617
DOI: 10.4103/ijmr.IJMR_1652_17 -
Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
Biology of Reproduction May 2021Zinc is a critical component in a number of conserved processes that regulate female germ cell growth, fertility, and pregnancy. During follicle development, a... (Review)
Review
Zinc is a critical component in a number of conserved processes that regulate female germ cell growth, fertility, and pregnancy. During follicle development, a sufficient intracellular concentration of zinc in the oocyte maintains meiotic arrest at prophase I until the germ cell is ready to undergo maturation. An adequate supply of zinc is necessary for the oocyte to form a fertilization-competent egg as dietary zinc deficiency or chelation of zinc disrupts maturation and reduces the oocyte quality. Following sperm fusion to the egg to initiate the acrosomal reaction, a quick release of zinc, known as the zinc spark, induces egg activation in addition to facilitating zona pellucida hardening and reducing sperm motility to prevent polyspermy. Symmetric division, proliferation, and differentiation of the preimplantation embryo rely on zinc availability, both during the oocyte development and post-fertilization. Further, the fetal contribution to the placenta, fetal limb growth, and neural tube development are hindered in females challenged with zinc deficiency during pregnancy. In this review, we discuss the role of zinc in germ cell development, fertilization, and pregnancy with a focus on recent studies in mammalian females. We further detail the fundamental zinc-mediated reproductive processes that have only been explored in non-mammalian species and speculate on the role of zinc in similar mechanisms of female mammals. The evidence collected over the last decade highlights the necessity of zinc for normal fertility and healthy pregnancy outcomes, which suggests zinc supplementation should be considered for reproductive age women at risk of zinc deficiency.
Topics: Animals; Female; Humans; Mammals; Mice; Rats; Reproduction; Sus scrofa; Zinc
PubMed: 33598687
DOI: 10.1093/biolre/ioab023 -
Human Reproduction Update Feb 2022Advanced maternal age is associated with decreased oocyte quantity and quality as well as uterine and placental dysfunctions. These changes lead to infertility,... (Review)
Review
BACKGROUND
Advanced maternal age is associated with decreased oocyte quantity and quality as well as uterine and placental dysfunctions. These changes lead to infertility, pregnancy complications and birth defects in the offspring. As the mean age of giving birth is increasing worldwide, prevention of age-associated infertility and pregnancy complications, along with the more frequent use of ART, become extremely important. Currently, significant research is being conducted to unravel the mechanisms underlying female reproductive aging. Among the potential mechanisms involved, recent evidence has suggested a contributing role for cellular senescence, a cellular state of irreversible growth arrest characterized by a hypersecretory and pro-inflammatory phenotype. Elucidating the role of senescence in female reproductive aging holds the potential for developing novel and less invasive therapeutic measures to prevent or even reverse female reproductive aging and increase offspring wellbeing.
OBJECTIVE AND RATIONALE
The review will summarize the positive and negative implications of cellular senescence in the pathophysiology of the female reproductive organs during aging and critically explore the use of novel senotherapeutics aiming to reverse and/or eliminate their detrimental effects. The focus will be on major senescence mechanisms of the ovaries, the uterus, and the placenta, as well as the potential and risks of using senotherapies that have been discovered in recent years.
SEARCH METHODS
Data for this review were identified by searches of MEDLINE, PubMed and Google Scholar. References from relevant articles using the search terms 'Cellular Senescence', 'Aging', 'Gestational age', 'Maternal Age', 'Anti-aging', 'Uterus', 'Pregnancy', 'Fertility', 'Infertility', 'Reproduction', 'Implant', 'Senolytic', 'Senostatic', 'Senotherapy' and 'Senotherapeutic' where selected. A total of 182 articles published in English between 2005 and 2020 were included, 27 of which focus on potential senotherapies for reproductive aging. Exclusion criteria were inclusion of the terms 'male' and 'plants'.
OUTCOMES
Aging is a major determinant of reproductive wellbeing. Cellular senescence is a basic aging mechanism, which can be exploited for therapeutic interventions. Within the last decade, several new strategies for the development and repurposing of drugs targeting senescent cells have emerged, such as modulators of the anti-inflammatory response, oxidative stress, DNA damage, and mitochondria and protein dysfunctions. Several studies of female reproductive aging and senotherapies have been discussed that show promising results for future interventions.
WIDER IMPLICATIONS
In most countries of the Organization for Economic Co-operation and Development, the average age at which women give birth is above 30 years. Currently, in countries such as the Netherlands, Australia, Spain, Finland, Germany and the UK, birth rates among 30- to 34-year-olds are now higher than in any other age groups. This review will provide new knowledge and scientific advancement on the senescence mechanisms during female reproductive aging, and benefit fundamental and clinical scientists and professionals in the areas of reproduction, cancer, immunobiology and fibrosis.
Topics: Aging; Cellular Senescence; Female; Humans; Infertility; Male; Placenta; Pregnancy; Pregnancy Complications; Reproduction; Senotherapeutics
PubMed: 34918084
DOI: 10.1093/humupd/dmab038 -
Current Protocols Dec 2022Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced...
Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced gametes. While understanding the likelihood of producing unbalanced conceptuses is critical for individuals to make reproductive decisions, risk estimates are difficult to obtain as most balanced translocations are unique. To improve reproductive risk estimates, Drs. Trunca and Mendell created models based on a logistic regression analysis of a dataset of over 6000 individuals from over 1000 translocation families. While risk assessments using these models have been offered as a free service for years, this protocol aims to create a sustainable model for genetics professionals to obtain risk estimates for their patients directly. This protocol guides the user through collecting clinical information, using a risk-generating Java program based on the models, and interpreting the program outputs. A practice tutorial is provided to ensure competency in interpretation prior to use. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Estimation of reproductive risks for balanced translocation carriers Basic Protocol 2: Practical examples of typical patient encounters with instructive interpretations.
Topics: Pregnancy; Female; Child; Humans; Translocation, Genetic; Reproduction; Heterozygote; Abortion, Spontaneous
PubMed: 36571718
DOI: 10.1002/cpz1.633 -
Nutrients Aug 2020Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological...
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Topics: Adult; Dietary Supplements; Dysmenorrhea; Endometriosis; Female; Humans; Insulin Resistance; Lipid Metabolism; Male; Menstrual Cycle; Polycystic Ovary Syndrome; Pregnancy; Reproduction; Zinc
PubMed: 32824334
DOI: 10.3390/nu12082464 -
International Journal of Molecular... Jun 2022The intention of this Special Edition was to collect review and original research articles that illustrate and stimulate the growing efforts to highlight the mechanisms...
The intention of this Special Edition was to collect review and original research articles that illustrate and stimulate the growing efforts to highlight the mechanisms of action of gonadotropins, as well as deepen our understanding of their biological roles in health and disease, aiming at revealing novel therapeutic opportunities in reproductive and regenerative medicine [...].
Topics: Gonadotropins; Reproduction; Virus Physiological Phenomena
PubMed: 35682981
DOI: 10.3390/ijms23116303 -
Drug Design, Development and Therapy 2023Female infertility and pregnancy maintenance are associate with various factors, including quantity and quality of oocytes, genital inflammation, endometriosis, and... (Review)
Review
Female infertility and pregnancy maintenance are associate with various factors, including quantity and quality of oocytes, genital inflammation, endometriosis, and other diseases. Women are even diagnosed as unexplained infertility or unexplained recurrent spontaneous abortion when failed to achieve pregnancy with current treatment, which are urgent clinical issues need to be addressed. Coenzyme Q10 (CoQ10) is a lipid-soluble electron carrier in the mitochondrial electron transport chain. It is not only essential for the mitochondria to produce energy, but also function as an antioxidant to maintain redox homeostasis in the body. Recently, the capacity of CoQ10 to reduce oxidative stress (OS), enhance mitochondrial activity, regulate gene expression and inhibit inflammatory responses, has been discovered as a novel adjuvant in male reproductive performance enhancing in both animal and human studies. Furthermore, CoQ10 is also proved to regulate immune balance, antioxidant, promote glucose and lipid metabolism. These properties will bring highlight for ovarian dysfunction reversing, ovulation ameliorating, oocyte maturation/fertilization promoting, and embryonic development optimizing. In this review, we systematically discuss the pleiotropic effects of CoQ10 in female reproductive disorders to investigate the mechanism and therapeutic potential to provide a reference in subsequent studies.
Topics: Pregnancy; Animals; Female; Male; Humans; Antioxidants; Reproduction; Ovulation; Adjuvants, Immunologic
PubMed: 37667786
DOI: 10.2147/DDDT.S386974