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Central and Local Modulators of Reproduction and Fertility: An Update

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

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 53631

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Prof. Dr. Rosaria Meccariello

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Department of Movement and Wellness Sciences, Parthenope University of Naples, I-80133 Naples, Italy
Interests: endocannabinoid system; endocannabinoids–GnRH–steroids crosstalk; kisspeptins; reproduction; HPG axis; spermatogenesis; spermatozoa; endocrine disruptors; epigenetics
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Dear Colleagues,

Reproduction and fertility depend on the hypothalamus–pituitary–gonad (HPG) axis. The key actor in HPG axis activity is the hypothalamic gonadotropin-releasing hormone (GnRH), a decapeptide able to induce the discharge of pituitary gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) which in turn sustain the production of sex steroids by gonads, with successful gametogenesis as a result. In addition to intricate endocrine communication routes, also paracrine and autocrine communications along the HPG axis ensure successful gametogenesis. In this respect, the list of centrally and peripherally produced modulators of reproduction is growing and deserves attention to preserve both reproduction and fertility trough the formation of high-quality gametes. In fact, reproduction is highly sensitive to environmental factors such as diet, stress or endocrine disruptors, among others, and the possibility of epigenetic modulation of reproduction with transgenerational outcomes has recently been raised. To date, several modulators exert their activity within the hypothalamus modulating the activity of GnRH secreting neurons in response to exogenous and endogenous environmental “cues”; similarly, peripherally produced modulators directly affect gametogenesis with effects on reproduction and fertility. Despite experimental evidence, molecular and epigenetic regulatory mechanisms of HPG activity remain to be fully elucidated yet, hence the need to fill this gap in order to devise clinically effective treatment strategies.

This Special issue aims at expanding the current knowledge on central and local modulators of reproduction and fertility in both physiological and pathological conditions and on their possible therapeutic exploitation. Experimental studies in in vitro and in vivo models, review articles, and clinical studies as well are all welcome for consideration.

Dr. Rosaria Meccariello
Guest Editor

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Keywords

Reproduction
Fertility
HPG axis
Testis
Ovary
Spermatogenesis
Ovogenesis
Gametes
GnRH
Gonadotropins
Sex steroids
Kisspeptins
GnIH
Metabolic sensors
Leptin
Endocannabinoids
Autocrine/paracrine regulators
Protein/peptide hormones
Lipid mediators
Epigenetics

Related Special Issue

Central and Local Modulators of Reproduction and Fertility: An Update 3.0 in International Journal of Molecular Sciences (9 articles)

Published Papers (13 papers)

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19 pages, 1502 KiB

Open AccessArticle

Kisspeptin Receptor on the Sperm Surface Reflects Epididymal Maturation in the Dog

by Alessia Gloria, Alberto Contri, Elena Mele, Silvia Fasano, Riccardo Pierantoni and Rosaria Meccariello

Int. J. Mol. Sci. 2021, 22(18), 10120; https://doi.org/10.3390/ijms221810120 - 19 Sep 2021

Cited by 9 | Viewed by 2547

Abstract

Alongside the well-known central modulatory role, the Kisspeptin system, comprising Kiss1, its cleavage products (Kisspeptins), and Kisspeptin receptor (Kiss1R), was found to regulate gonadal functions in vertebrates; however, its functional role in the male gamete and its localization during maturation have been poorly understood. The present study analyzed Kisspeptin system in dog testis and spermatozoa recovered from different segments of the epididymis, with focus on Kiss1R on sperm surface alongside the maturation during epididymal transit, demonstrated by modification in sperm kinetic, morphology, and protamination. The proteins Kiss1 and Kiss1R were detected in dog testis. The receptor Kiss1R only was detected in total protein extracts from epididymis spermatozoa, whereas dot blot revealed Kiss1 immunoreactivity in the epidydimal fluid. An increase of the Kiss1R protein on sperm surface along the length of the epididymis, with spermatozoa in the tail showing plasma membrane integrity and Kiss1R protein (p < 0.05 vs. epididymis head and body) was observed by flow cytometry and further confirmed by epifluorescence microscopy and Western blot carried on sperm membrane preparations. In parallel, during the transit in the epididymis spermatozoa significantly modified their ability to move and the pattern of motility; a progressive increase in protaminization also occurred. In conclusion, Kisspeptin system was detected in dog testis and spermatozoa. Kiss1R trafficking toward plasma membrane along the length of the epididymis and Kiss1 in epididymal fluid suggested a new functional role of the Kisspeptin system in sperm maturation and storage. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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14 pages, 1410 KiB

Open AccessArticle

Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior

by Damien Hunter, Kee Heng, Navdeep Mann, Ravinder Anand-Ivell and Richard Ivell

Int. J. Mol. Sci. 2021, 22(8), 4163; https://doi.org/10.3390/ijms22084163 - 17 Apr 2021

Cited by 16 | Viewed by 2007

Abstract

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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10 pages, 3113 KiB

Open AccessArticle

SIRT1 Expression and Regulation in the Primate Testis

by Fazal Wahab, Ignacio Rodriguez Polo and Rüdiger Behr

Int. J. Mol. Sci. 2021, 22(6), 3207; https://doi.org/10.3390/ijms22063207 - 22 Mar 2021

Cited by 6 | Viewed by 2214

Abstract

The epigenetic mechanisms controlling germ cell development and differentiation are still not well understood. Sirtuin-1 (SIRT1) is a nicotinamide adenosine dinucleotide (NAD)-dependent histone deacetylase and belongs to the sirtuin family of deacetylases. It catalyzes the removal of acetyl groups from a number of protein substrates. Some studies reported a role of SIRT1 in the central and peripheral regulation of reproduction in various non-primate species. However, testicular SIRT1 expression and its possible role in the testis have not been analyzed in primates. Here, we document expression of SIRT1 in testes of different primates and some non-primate species. SIRT1 is expressed mainly in the cells of seminiferous tubules, particularly in germ cells. The majority of SIRT1-positive germ cells were in the meiotic and postmeiotic phase of differentiation. However, SIRT1 expression was also observed in selected premeiotic germ cells, i.e., spermatogonia. SIRT1 co-localized in spermatogonia with irisin, an endocrine factor specifically expressed in primate spermatogonia. In marmoset testicular explant cultures, SIRT1 transcript levels are upregulated by the addition of irisin as compared to untreated controls explants. Rhesus macaques are seasonal breeders with high testicular activity in winter and low testicular activity in summer. Of note, SIRT1 mRNA and SIRT1 protein expression are changed between nonbreeding (low spermatogenesis) and breeding (high spermatogenesis) season. Our data suggest that SIRT1 is a relevant factor for the regulation of spermatogenesis in primates. Further mechanistic studies are required to better understand the role of SIRT1 during spermatogenesis. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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16 pages, 2015 KiB

Open AccessArticle

Knockout of the Glucocorticoid Receptor Impairs Reproduction in Female Zebrafish

by Francesca Maradonna, Giorgia Gioacchini, Valentina Notarstefano, Camilla Maria Fontana, Filippo Citton, Luisa Dalla Valle, Elisabetta Giorgini and Oliana Carnevali

Int. J. Mol. Sci. 2020, 21(23), 9073; https://doi.org/10.3390/ijms21239073 - 28 Nov 2020

Cited by 16 | Viewed by 2427

Abstract

The pleiotropic effects of glucocorticoids in metabolic, developmental, immune and stress response processes have been extensively investigated; conversely, their roles in reproduction are still less documented. It is well known that stress or long-lasting therapies can cause a strong increase in these hormones, negatively affecting reproduction. Moreover, the need of glucocorticoid (GC) homeostatic levels is highlighted by the reduced fertility reported in the zebrafish glucocorticoid receptor mutant (nr3c1^ia30/ia30) line (hereafter named gr^−/−). Starting from such evidence, in this study, we have investigated the role of glucocorticoid receptor (Gr) in the reproduction of female zebrafish. Key signals orchestrating the reproductive process at the brain, liver, and ovarian levels were analyzed using a multidisciplinary approach. An impairment of the kiss-GnRH system was observed at the central level in (gr^−/−) mutants as compared to wild-type (wt) females while, in the liver, vitellogenin (vtg) mRNA transcription was not affected. Changes were instead observed in the ovary, particularly in maturing and fully grown follicles (classes III and IV), as documented by the mRNA levels of signals involved in oocyte maturation and ovulation. Follicles isolated from gr^−/− females displayed a decreased level of signals involved in the acquisition of competence and maturation, causing a reduction in ovulation with respect to wt females. Fourier transform infrared imaging (FTIRI) analysis of gr^−/− follicle cytoplasm showed major changes in macromolecule abundance and distribution with a clear alteration of oocyte composition. Finally, differences in the molecular structure of the zona radiata layer of gr^−/− follicles are likely to contribute to the reduced fertilization rate observed in mutants. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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15 pages, 1246 KiB

Open AccessArticle

Bisphenol A Deranges the Endocannabinoid System of Primary Sertoli Cells with an Impact on Inhibin B Production

by Gianna Rossi, Beatrice Dufrusine, Anna Rita Lizzi, Carla Luzi, Alessandra Piccoli, Filomena Fezza, Roberto Iorio, Gabriele D’Andrea, Enrico Dainese, Sandra Cecconi and Mauro Maccarrone

Int. J. Mol. Sci. 2020, 21(23), 8986; https://doi.org/10.3390/ijms21238986 - 26 Nov 2020

Cited by 15 | Viewed by 2769

Abstract

Bisphenol A (BPA) is an endocrine disruptor that negatively affects spermatogenesis, a process where Sertoli cells play a central role. Thus, in the present study we sought to ascertain whether BPA could modulate the endocannabinoid (eCB) system in exposed mouse primary Sertoli cells. Under our experimental conditions, BPA turned out to be cytotoxic to Sertoli cells with an half-maximal inhibitory concentration (IC₅₀) of ~6.0 µM. Exposure to a non-cytotoxic dose of BPA (i.e., 0.5 μM for 48 h) increased the expression levels of specific components of the eCB system, namely: type-1 cannabinoid (CB₁) receptor and diacylglycerol lipase-α (DAGL-α), at mRNA level, type-2 cannabinoid (CB₂) receptor, transient receptor potential vanilloid 1 (TRPV1) receptors, and DAGL-β, at protein level. Interestingly, BPA also increased the production of inhibin B, but not that of transferrin, and blockade of either CB₂ receptor or TRPV1 receptor further enhanced the BPA effect. Altogether, our study provides unprecedented evidence that BPA deranges the eCB system of Sertoli cells towards CB₂- and TRPV1-dependent signal transduction, both receptors being engaged in modulating BPA effects on inhibin B production. These findings add CB₂ and TRPV1 receptors, and hence the eCB signaling, to the other molecular targets of BPA already known in mammalian cells. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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18 pages, 2453 KiB

Open AccessArticle

The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells

by Valentina Notarstefano, Giorgia Gioacchini, Elisabetta Giorgini, Nina Montik, Andrea Ciavattini, Anna Rita Polidori, Fulvia Antonia Candela, Lisa Vaccari, Maurizio Cignitti and Oliana Carnevali

Int. J. Mol. Sci. 2020, 21(19), 7124; https://doi.org/10.3390/ijms21197124 - 27 Sep 2020

Cited by 12 | Viewed by 2235

Abstract

Different Follicle Stimulating Hormone (FSH) formulation and Luteinizing Hormone (LH) are used in Assisted Reproductive Technology (ART) to induce follicles development and oocytes maturation, but it is still under debate which protocol is to be preferred. In the present study, the different effects on cumulus cells (CCs) of three controlled ovarian stimulation (COS) protocols, based on urinary FSH, recombinant FSH, or human Menopausal Gonadotropin (hMG) administration, were assessed. CCs were obtained from 42 normal-responders women undergoing COS, randomly divided into three groups according to the used gonadotropin formulation. Differences were found in the expression of genes belonging to the endocannabinoid system (the receptors CNR1, CNR2 and TRPV1, and the enzymes involved in the metabolisms of anandamide, NAPE-PLD and FAAH, and 2-acylglycerol, DAGL and MAGL); consistently, changes in lipid (PPARα, and FASN) and carbohydrate (GLUT1 and GLUT9) metabolisms, in CCs’ macromolecules composition (highlighted by Fourier Transform Infrared Microspectroscopy, FTIRM), and in the number of retrieved oocytes were found. For the first time, statistically significant evidence on the differences related to each COS protocol on the endocannabinoid system, metabolism and macromolecular composition of CCs was found, representing a proof of concept to be further confirmed in a larger cohort of patients. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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14 pages, 3756 KiB

Open AccessArticle

Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice

by Santosh Rijal, Dong Hyu Cho, Seon-Ah Park, Seon Hui Jang, István M. Ábrahám and Seong Kyu Han

Int. J. Mol. Sci. 2020, 21(17), 5991; https://doi.org/10.3390/ijms21175991 - 20 Aug 2020

Cited by 8 | Viewed by 3230

Abstract

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na⁺ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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Review

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27 pages, 2300 KiB

Open AccessReview

Luteinizing Hormone Regulation of Inter-Organelle Communication and Fate of the Corpus Luteum

by Emilia Przygrodzka, Michele R. Plewes and John S. Davis

Int. J. Mol. Sci. 2021, 22(18), 9972; https://doi.org/10.3390/ijms22189972 - 15 Sep 2021

Cited by 18 | Viewed by 5468

Abstract

The corpus luteum is an endocrine gland that synthesizes the steroid hormone progesterone. luteinizing hormone (LH) is a key luteotropic hormone that stimulates ovulation, luteal development, progesterone biosynthesis, and maintenance of the corpus luteum. Luteotropic and luteolytic factors precisely regulate luteal structure and function; yet, despite recent scientific progress within the past few years, the exact mechanisms remain largely unknown. In the present review, we summarize the recent progress towards understanding cellular changes induced by LH in steroidogenic luteal cells. Herein, we will focus on the effects of LH on inter-organelle communication and steroid biosynthesis, and how LH regulates key protein kinases (i.e., AMPK and MTOR) responsible for controlling steroidogenesis and autophagy in luteal cells. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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13 pages, 1037 KiB

Open AccessReview

Methylation: An Ineluctable Biochemical and Physiological Process Essential to the Transmission of Life

by Yves Menezo, Patrice Clement, Arthur Clement and Kay Elder

Int. J. Mol. Sci. 2020, 21(23), 9311; https://doi.org/10.3390/ijms21239311 - 07 Dec 2020

Cited by 22 | Viewed by 3838

Abstract

Methylation is a universal biochemical process which covalently adds methyl groups to a variety of molecular targets. It plays a critical role in two major global regulatory mechanisms, epigenetic modifications and imprinting, via methyl tagging on histones and DNA. During reproduction, the two genomes that unite to create a new individual are complementary but not equivalent. Methylation determines the complementary regulatory characteristics of male and female genomes. DNA methylation is executed by methyltransferases that transfer a methyl group from S-adenosylmethionine, the universal methyl donor, to cytosine residues of CG (also designated CpG). Histones are methylated mainly on lysine and arginine residues. The methylation processes regulate the main steps in reproductive physiology: gametogenesis, and early and late embryo development. A focus will be made on the impact of assisted reproductive technology and on the impact of endocrine disruptors (EDCs) via generation of oxidative stress. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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24 pages, 316 KiB

Open AccessReview

Endocrine-Disrupting Air Pollutants and Their Effects on the Hypothalamus-Pituitary-Gonadal Axis

by Elizabeth C. Plunk and Sean M. Richards

Int. J. Mol. Sci. 2020, 21(23), 9191; https://doi.org/10.3390/ijms21239191 - 02 Dec 2020

Cited by 45 | Viewed by 4196

Abstract

Anthropogenic endocrine-disrupting chemicals (EDCs) can contaminate air, soil, and water. Human exposures to EDCs occur through inhalation, absorption, and ingestion. EDCs act by disrupting various pathways in the endocrine system. When the hypothalamic–pituitary–gonadal (HPG) axis is disrupted by EDCs, there can be effects on fertility in both men and women. Not only can fertility be indirectly affected by EDC disruptions of the HPG axis, but EDCs can also directly affect the menstrual cycle and sperm morphology. In this review, we will discuss the current findings on EDCs that can be inhaled. This review examines effects of exposure to prominent EDCs: brominated and organophosphate flame retardants, diesel exhaust, polycyclic aromatic hydrocarbons, cadmium and lead, TCDD, and polychlorinated biphenyls on fertility through alterations that disrupt the HPG axis and fertility through inhalation. Although the studies included herein include multiple exposure routes, all the studies indicate receptor interactions that can occur from inhalation and the associated effects of all compounds on the HPG axis and subsequent fertility. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

23 pages, 1497 KiB

Open AccessReview

Exogenous Oestrogen Impacts Cell Fate Decision in the Developing Gonads: A Potential Cause of Declining Human Reproductive Health

by Melanie K. Stewart, Deidre M. Mattiske and Andrew J. Pask

Int. J. Mol. Sci. 2020, 21(21), 8377; https://doi.org/10.3390/ijms21218377 - 08 Nov 2020

Cited by 11 | Viewed by 3246

Abstract

The increasing incidence of testicular dysgenesis syndrome-related conditions and overall decline in human fertility has been linked to the prevalence of oestrogenic endocrine disrupting chemicals (EDCs) in the environment. Ectopic activation of oestrogen signalling by EDCs in the gonad can impact testis and ovary function and development. Oestrogen is the critical driver of ovarian differentiation in non-mammalian vertebrates, and in its absence a testis will form. In contrast, oestrogen is not required for mammalian ovarian differentiation, but it is essential for its maintenance, illustrating it is necessary for reinforcing ovarian fate. Interestingly, exposure of the bi-potential gonad to exogenous oestrogen can cause XY sex reversal in marsupials and this is mediated by the cytoplasmic retention of the testis-determining factor SOX9 (sex-determining region Y box transcription factor 9). Oestrogen can similarly suppress SOX9 and activate ovarian genes in both humans and mice, demonstrating it plays an essential role in all mammals in mediating gonad somatic cell fate. Here, we review the molecular control of gonad differentiation and explore the mechanisms through which exogenous oestrogen can influence somatic cell fate to disrupt gonad development and function. Understanding these mechanisms is essential for defining the effects of oestrogenic EDCs on the developing gonads and ultimately their impacts on human reproductive health. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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21 pages, 12282 KiB

Open AccessReview

The Central Role of Cadherins in Gonad Development, Reproduction, and Fertility

by Rafał P. Piprek, Malgorzata Kloc, Paulina Mizia and Jacek Z. Kubiak

Int. J. Mol. Sci. 2020, 21(21), 8264; https://doi.org/10.3390/ijms21218264 - 04 Nov 2020

Cited by 27 | Viewed by 6918

Abstract

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood–testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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17 pages, 1360 KiB

Open AccessReview

Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility

by Francesca Sciarra, Edoardo Franceschini, Federica Campolo, Daniele Gianfrilli, Francesco Pallotti, Donatella Paoli, Andrea M. Isidori and Mary Anna Venneri

Int. J. Mol. Sci. 2020, 21(11), 3943; https://doi.org/10.3390/ijms21113943 - 30 May 2020

Cited by 58 | Viewed by 11603

Abstract

Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders. Full article

(This article belongs to the Special Issue Central and Local Modulators of Reproduction and Fertility: An Update)

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