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The Malaysian Journal of Medical... Apr 2022Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological as well as pathological importance. Physiological mechanisms mediated by NO mainly... (Review)
Review
Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological as well as pathological importance. Physiological mechanisms mediated by NO mainly include angiogenesis, growth, puberty and senescence. NO has vital roles in normal reproduction, including steroidogenesis, gametogenesis and the regulation of germ-cell apoptosis. In females, NO stimulates an inflammatory cascade to induce ovulation, decreases steroidogenesis in luteal and granulosa cells, and acts as a paracrine factor to mediate reproductive cycles and implantation. In males, NO is a key player for steroidogenesis, erectile functions, sperm capacitation and acrosome reaction. Moreover, NO is also a regulator of Sertoli cell-germ cell interaction and maintenance of the blood-testis barrier. In pathological conditions such as infections, increased nitric oxide synthase (NOS) activities stimulate the excessive synthesis of NO which acts as a proinflammatory mediator inducing oxidative stress (OS), which is detrimental to reproductive functions in both males and females. During impregnation, the overproduction of NO results in uterine epithelial cell inflammation and immune rejection of implantation. Excessive NO synthesis disrupts gonadal functions, and induces germ cell apoptosis and oxidative damage to the germ cells. This review elucidates how the differences in NO expression levels account for its beneficial and adverse impacts upon male and female fertility.
PubMed: 35528812
DOI: 10.21315/mjms2022.29.2.3 -
Frontiers in Bioscience (Elite Edition) Jan 2021Melatonin, a hormone which is primarily released by the pineal gland, has a wide range of actions in the female reproductive tract. While the melatonin receptor subtype,... (Review)
Review
Melatonin, a hormone which is primarily released by the pineal gland, has a wide range of actions in the female reproductive tract. While the melatonin receptor subtype, MT3, has been identified in amphibian animals and birds, in humans and other mammals, melatonin acts through, MT1 and MT2 receptor subtypes which are expressed in human ovaries. The rhythmic release of melatonin starts at puberty and continues throughout fertile female life, affecting and regulating diverse ovarian functions. Here, we discuss the importance of melatonin in regulating folliculogenesis, oocyte quality, ovulation and luteal function, sex steroid receptor gene expression, ovarian steroidogenesis including the production and steroidogenic enzyme activities in the egg and thecal cells. Melatonin improves the egg quality and increases the chance of success of in vitro fertilization (IVF). In view of such extensive actions, melatonin is central to the fertility in females. The objective of this review is to recapitulate the current understanding of the role of melatonin and its receptors.
Topics: Animals; Female; Humans; Melatonin; Ovary; Receptor, Melatonin, MT2; Receptors, Melatonin
PubMed: 33048779
DOI: 10.2741/875 -
Cell Proliferation Dec 2023Normal ovarian development is necessary for the production of healthy oocytes. However, the characteristics of oocytes development at different stages and the regulatory...
Normal ovarian development is necessary for the production of healthy oocytes. However, the characteristics of oocytes development at different stages and the regulatory relationship between oocytes and somatic cells remain to be fully explained. Here, we combined scRNA-seq and spatial transcriptomic sequencing to profile the transcriptomic atlas of developing ovarian of the rat. We identified four components from developing granulosa cells including cumulus, primitive, mural, and luteal cells, and constructed their differential transcriptional regulatory networks. Several novel growth signals from oocytes to cumulus cells were identified, such as JAG1-NOTCH2 and FGF9-FGFR2. Moreover, we observed three cumulus sequential phases during follicle development determined by the key transcriptional factors in each cumulus phase (Bckaf1, Gata6, Cebpb, etc.), as well as the potential pinpointed roles of macrophages in luteal regression. Altogether, the single-cell spatial transcriptomic profile of the ovary provides not only a new research dimension for temporal and spatial analysis of ovary development, but also valuable data resources and a research basis for in-depth excavation of the mechanisms of mammalian ovary development.
Topics: Female; Rats; Animals; Ovary; Oocytes; Granulosa Cells; Oogenesis; Transcriptome; Mammals
PubMed: 37309718
DOI: 10.1111/cpr.13516 -
The FEBS Journal May 2022Gonad development is a highly regulated process that coordinates cell specification and morphogenesis to produce sex-specific organ structures that are required for... (Review)
Review
Gonad development is a highly regulated process that coordinates cell specification and morphogenesis to produce sex-specific organ structures that are required for fertility, such as testicular seminiferous tubules and ovarian follicles. While sex determination occurs within specialized gonadal supporting cells, sexual differentiation is evident throughout the entire organ, including within the interstitial compartment, which contains immune cells and vasculature. While immune and vascular cells have been traditionally appreciated for their supporting roles during tissue growth and homeostasis, an increasing body of evidence supports the idea that these cell types are critical drivers of sexually dimorphic morphogenesis of the gonad. Myeloid immune cells, such as macrophages, are essential for multiple aspects of gonadogenesis and fertility, including for forming and maintaining gonadal vasculature in both sexes at varying stages of life. While vasculature is long known for supporting organ growth and serving as an export mechanism for gonadal sex steroids in utero, it is also an important component of fetal testicular morphogenesis and differentiation; additionally, it is vital for ovarian corpus luteal function and maintenance of pregnancy. These findings point toward a new paradigm in which immune cells and blood vessels are integral components of sexual differentiation and organogenesis. In this review, we discuss the state of the field regarding the diverse roles of immune and vascular cells during organogenesis of the testis and ovary and highlight outstanding questions in the field that could stimulate new research into these previously underappreciated constituents of the gonad.
Topics: Female; Gonads; Humans; Male; Organogenesis; Ovary; Pregnancy; Sex Differentiation; Testis
PubMed: 33774913
DOI: 10.1111/febs.15848 -
Molecular and Cellular Endocrinology Sep 2020Progesterone, a critical hormone in reproduction, is a key sex steroid in the establishment and maintenance of early pregnancy and serves as an intermediary for... (Review)
Review
Progesterone, a critical hormone in reproduction, is a key sex steroid in the establishment and maintenance of early pregnancy and serves as an intermediary for synthesis of other steroid hormones. Progesterone production from the corpus luteum is a tightly regulated process which is stimulated and maintained by multiple factors, both systemic and local. Multiple regulatory systems, including classic mediators of gonadotropin stimulation such as the cAMP/PKA pathway and TGFβ-mediated signaling pathways, as well as local production of hormonal factors, exist to promote granulosa cell function and physiological fine-tuning of progesterone levels. In this manuscript, we provide an updated narrative review of the known mediators of human luteal progesterone and highlight new observations regarding this important process, focusing on studies published within the last five years. We will also review recent evidence suggesting that this complex system of progesterone production is sensitive to disruption by exogenous environmental chemicals that can mimic or interfere with the activities of endogenous hormones.
Topics: Animals; Chorionic Gonadotropin; Corpus Luteum; Female; Granulosa Cells; Humans; Progesterone
PubMed: 32610113
DOI: 10.1016/j.mce.2020.110930 -
Frontiers in Medicine 2023
PubMed: 38020104
DOI: 10.3389/fmed.2023.1308488 -
Molecular and Cellular Endocrinology Jul 2021A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics...
A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby inhibiting the cell cycle. Expression of CYP17A1 was upregulated in High A4 GCs presumably due to reduced FOS mRNA expression compared to Control granulosa cells. Furthermore, comparisons of High A4 GC with thecal and luteal cell transcriptomes indicated an altered cellular identity and function contributing to a PCOS-like phenotype.
Topics: Androstenedione; Animals; Cattle; Cell Proliferation; Cells, Cultured; Cellular Microenvironment; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Granulosa Cells; MicroRNAs; Models, Biological; Oligonucleotide Array Sequence Analysis; Primary Cell Culture
PubMed: 33905753
DOI: 10.1016/j.mce.2021.111288 -
Molecular and Cellular Endocrinology Jun 2021Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system... (Review)
Review
Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system plays a key role in this adaptation process. One of its components, prorenin, is released in significant amounts from the ovary and uteroplacental unit. This review describes the sources of prorenin in the periconception period and in pregnancy, including its modulation by in-vitro fertilization protocols, and discusses its potential effects, among others focusing on preeclampsia. It ends with discussing the long-term consequences, even in later life, of inappropriate renin-angiotensin-aldosterone system activity in pregnancy and offers directions for future research. Ultimately, a full understanding of the role of prorenin periconceptionally and during pregnancy will help to develop tools to diagnose and/or prevent reproductive complications.
Topics: Angiotensin I; Angiotensinogen; Female; Fertilization in Vitro; Gene Expression Regulation; Humans; Ovary; Placenta; Pre-Eclampsia; Pregnancy; Renin; Renin-Angiotensin System; Signal Transduction; Uterus
PubMed: 33878417
DOI: 10.1016/j.mce.2021.111281 -
Molecular and Cellular Endocrinology Feb 2021Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system... (Review)
Review
Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system plays a key role in this adaptation process. One of its components, prorenin, is released in significant amounts from the ovary and uteroplacental unit. This review describes the sources of prorenin in the periconception period and in pregnancy, including its modulation by in-vitro fertilization protocols, and discusses its potential effects, among others focusing on preeclampsia. It ends with discussing the long-term consequences, even in later life, of inappropriate renin-angiotensin-aldosterone system activity in pregnancy and offers directions for future research. Ultimately, a full understanding of the role of prorenin periconceptionally and during pregnancy will help to develop tools to diagnose and/or prevent reproductive complications.
Topics: Animals; Female; Hemodynamics; Humans; Models, Biological; Pre-Eclampsia; Pregnancy; Protein Biosynthesis; Renin; Renin-Angiotensin System
PubMed: 33340569
DOI: 10.1016/j.mce.2020.111118 -
Frontiers in Reproductive Health 2020Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment... (Review)
Review
Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment of pregnancy. During the LP, the corpus luteum (CL) secretes progesterone and some other hormones that are essential to prepare the uterus for implantation and further development of the embryo, the function known as uterine receptivity. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, but also in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. LPD is particularly frequent in treatments using assisted reproductive technology (ART). Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. Altogether, these treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL. In addition to problems of endometrial receptivity for embryos, LPD also leads to dysfunction of the local uterine immune system, with an increased risk of embryo rejection, abnormally high uterine contractility, and restriction of uterine blood flow. There are two alternatives of LPD prevention: a direct administration of exogenous progesterone to restore the physiological progesterone serum concentration independently of the CL function, on the one hand, and treatments aimed to stimulate the CL activity so as to increase endogenous progesterone production, on the other hand. In case of pregnancy, some kind of LP support is often needed until the luteal-placental shift occurs. If LPD is caused by defective response of the endometrium and uterine immune cells to normal concentrations of progesterone, a still poorly defined condition, symptomatic treatments are the only available solution currently available.
PubMed: 36304702
DOI: 10.3389/frph.2020.595183