Expression of interleukin-1ß and its receptor in human granulosa cells and their association with steroidogenesis.

This study aimed to investigate whether interleukin 1ß (IL-1ß) and soluble IL-1 receptor 2 (sIL-1R2) are expressed in human granulosa cells (GCs) and relate to ovarian steroidogenesis. Ninety-six women undergoing in vitro fertilization (IVF) were recruited. RT-PCR and immunocytochemistry were used to detect mRNAs and proteins of IL-1ß and IL-1R2, respectively. The steroidogenesis of primary cultured GCs was evaluated following treatment with either IL-1ß alone or IL-1ß and FSH in combination. There were positive correlations between serum IL-1ß and serum progesterone (r = 0.220, p = 0.032) and follicular fluid (FF) estradiol (r = 0.242, p = 0.018). Additionally, serum and FF sIL-1R2 were negatively and positively correlated with FF estradiol (r = -0.376, p = 0.005) and FF progesterone (r = 0.434, p = 0.001), respectively. The mRNA and protein expression of IL-1ß and IL-1R2 became evident in GCs. IL-1ß alone significantly increased estradiol secretion from GCs, but in the presence of FSH, it could notably promote progesterone secretion in addition to estradiol. In conclusion, IL-1ß and sIL-1R2 are expressed in human GCs and substantially contribute to ovarian steroidogenesis, suggesting that the IL-1ß system may be a potential target for optimizing ovarian hyperstimulation and steroidogenesis in IVF cycles.

Does Anti-Müllerian hormone vary during a menstrual cycle? A systematic review and meta-analysis.

OBJECTIVE: Numerous studies have indicated that the level of the Anti-Müllerian hormone (AMH), one of the main markers for the ovarian reserve, does not fluctuate throughout a menstrual cycle, while some studies have rejected this finding. The purpose of this systematic and meta-analysis study is to consensus on all contradictory studies that have measured AMH levels throughout the menstrual cycle and to investigate the exact extent of AMH variation in a cycle. METHODS: The protocol for this meta-analysis was registered at PROSPERO before data extraction. Relevant studies were identified by systematic search in PubMed, ScienceDirect, Embase, Cochrane Library, and Google Scholar with no limitation on publication date. Longitudinal studies which have evaluated AMH levels in the follicular and luteal phases of an unstimulated (natural) menstrual cycle in healthy women without endocrinology or ovarian disorders were included. We used the JBI Critical Appraisal Checklist for assessing the quality of studies found eligible for meta-analysis. RESULTS: A total of 11 studies involving 733 women with regular menstrual cycles were included. The results showed that the AMH level in the follicular phase was significantly higher than in the luteal phase (95% Cl = 0.11 [0.01 to 0.21]; p < 0.05) and it varies about 11.5% from the luteal phase. The analysis of studies which had also examined the ovulatory phase (n = 380) showed that the serum levels of AMH in the ovulatory phase (about 2.02 ng/ml) did not significantly vary compared to follicular (95% Cl = 0.11 [-0.10 to 0.33]; p = 0.30) and luteal (95% Cl = 0.06 [-0.08 to 0.20]; p = 0.43) phases. CONCLUSIONS: According to the results of this study, AMH levels differ between follicular and luteal phases which might be due to ovarian response to the gonadotropins. It seems the phase of AMH measurement needs to be considered for interpretation of the serum AMH test.

Melatonin as a Therapeutic Agent for the Inhibition of Hypoxia-Induced Tumor Progression: A Description of Possible Mechanisms Involved.

Hypoxia has an important role in tumor progression via the up-regulation of growth factors and cellular adaptation genes. These changes promote cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism in favor of cancer development. Hypoxia also plays a central role in determining the resistance of tumors to chemotherapy. Hypoxia of the tumor microenvironment provides an opportunity to develop new therapeutic strategies that may selectively induce apoptosis of the hypoxic cancer cells. Melatonin is well known for its role in the regulation of circadian rhythms and seasonal reproduction. Numerous studies have also documented the anti-cancer properties of melatonin, including anti-proliferation, anti-angiogenesis, and apoptosis promotion. In this paper, we hypothesized that melatonin exerts anti-cancer effects by inhibiting hypoxia-induced pathways. Considering this action, co-administration of melatonin in combination with other therapeutic medications might increase the effectiveness of anti-cancer drugs. In this review, we discussed the possible signaling pathways by which melatonin inhibits hypoxia-induced cancer cell survival, invasion, migration, and metabolism, as well as tumor angiogenesis.

Role of adipokines in embryo implantation.

Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo-maternal crosstalk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo-maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.

microRNAs in the pathogenesis of non-obstructive azoospermia: the underlying mechanisms and therapeutic potentials.

miRNAs are involved in different biological processes, including proliferation, differentiation, and apoptosis. Interestingly, 38% of the X chromosome-linked miRNAs are testis-specific and have crucial roles in regulating the renewal and cell cycle of spermatogonial stem cells. Previous studies demonstrated that abnormal expression of spermatogenesis-related miRNAs could lead to nonobstructive azoospermia (NOA). Moreover, differential miRNAs expression in seminal plasma of NOA patients has been reported compared to normozoospermic men. However, the role of miRNAs in NOA pathogenesis and the underlying mechanisms have not been comprehensively studied. Therefore, the aim of this review is to mechanistically describe the role of miRNAs in the pathogenesis of NOA and discuss the possibility of using the miRNAs as therapeutic targets.Abbreviations: AMO: anti-miRNA antisense oligonucleotide; AZF: azoospermia factor region; CDK: cyclin-dependent kinase; DAZ: deleted in azoospermia; ESCs: embryonic stem cells; FSH: follicle-stimulating hormone; ICSI: intracytoplasmic sperm injection; JAK/STAT: Janus kinase/signal transducers and activators of transcription; miRNA: micro-RNA; MLH1: Human mutL homolog l; NF-κB: Nuclear factor-kappa B; NOA: nonobstructive azoospermia; OA: obstructive azoospermia; PGCs: primordial germ cells; PI3K/AKT: Phosphatidylinositol 3-kinase/protein kinase B; Rb: retinoblastoma tumor suppressor; ROS: Reactive Oxygen Species; SCOS: Sertoli cell-only syndrome; SIRT: sirtuin; SNPs: single nucleotide polymorphisms; SSCs: spermatogonial stem cells; TESE: testicular sperm extraction; TGF-ß: transforming growth factor-beta.

Toxic effect of light on oocyte and pre-implantation embryo: a systematic review.

In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs.

Omics in Seminal Plasma: An Effective Strategy for Predicting Sperm Retrieval Outcome in Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is a severe form of male factor infertility resulting from the impairment of sperm production. Surgical sperm retrieval followed by intracytoplasmic sperm injection (ICSI) is the only alternative for NOA patients to have their own genetic children. Nevertheless, due to an approximately 50% chance of success, harvesting sperm from these patients remains challenging. Thus, discovering noninvasive biomarkers, which are able to reliably predict the probability of sperm acquisition, not only can eliminate the risk of surgery but also can lower the costs of NOA diagnosis and treatment. Seminal plasma is the non-cellular and liquid portion of the ejaculate that consists of the secretions originating from testes and male accessory glands. In past years, a wide range of biomolecules including DNAs, RNAs, proteins, and metabolic intermediates have been identified by omics techniques in human seminal plasma. The current review aimed to briefly describe genomic, transcriptomic, proteomic, and metabolomic profiles of human seminal plasma in an attempt to introduce potential candidate noninvasive biomarkers for sperm-retrieval success in men with NOA.

Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

Role of adipokines in the ovarian function: Oogenesis and steroidogenesis.

Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.

Cytokines in embryonic secretome as potential markers for embryo selection.

Despite performing certain morphological assessments for selecting the best embryo for transfer, the results have not been satisfactory. Given the global tendency for performing quick and noninvasive tests for embryo selection, great efforts have been made to discover the predictive biomarkers of embryo implantation potential. In recent years, many factors have been detected in embryo culture media as a major source of embryo secretions. Previous studies have evaluated cytokines, miRNAs, extracellular vesicles, and other factors such as leukemia inhibitory factor, colony-stimulating factor, reactive oxygen species, soluble human leukocyte antigen G, amino acids, and apolipoproteins in these media. Given the key role of cytokines in embryo implantation, these factors can be considered promising molecules for predicting the implantation success of assisted reproductive technology (ART). The present study was conducted to review embryo-secreted molecules as potential biomarkers for embryo selection in ART.

Effects of bacteria on male fertility: Spermatogenesis and sperm function.

Bacterial infection can negatively affect different parts of the male genital tract and subsequently cause impaired spermatogenesis and male fertility. However, most of the previous studies have focused on the infected organs of the male genital tract and there are not many studies that investigated the direct effect of bacteria on sperm and their mechanism of action. Interestingly, bacteria can induce different damages on sperm cells such as DNA fragmentation, cell membrane peroxidation, and acrosome impairment. Such negative effects can be mediated by bacteria-secreted toxins and metabolites or by direct attachment of bacteria on the sperm cells and subsequent activation of signaling pathways related to oxidative stress, apoptosis, and inflammation. These bacteria-induced changes can impair semen parameters and subsequently cause infertility. Given the significant destructive effect of some bacteria on sperm function and male fertility, in this study, we reviewed the impact of male urogenital bacteria on spermatogenesis and sperm functions as well as the underlying mechanisms by which the bacteria can damage sperm.