The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation.

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Hyaluronic Acid: A Review of the Drug Delivery Capabilities of This Naturally Occurring Polysaccharide

Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos.

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes—COCs) and male (spermatozoa), oxidative stress was measured by CM-H2DCFDA assay and key ROS scavengers (SOD1, SOD2, GPX1, GPX4, CAT) were quantified at the mRNA and protein levels using qPCR and Western blot (COCs)/immunofluorescence (sperm). Either gamete was treated in five groups: control, vehicle, and 0.05 mg/mL of BPA, BPS, or BPF. Our results show elevated ROS in BPA-treated COCs but decreased production in BPS- and BPF-treated spermatozoa. Additionally, both mRNA and protein expression of SOD2, GPX1, and GPX4 were decreased in BPA-treated COCs (p < 0.05). In sperm, motility (p < 0.03), but not morphology, was significantly altered by bisphenols. SOD1 mRNA expression was significantly increased, while GPX4 was significantly reduced. These results support BPA’s ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm. However, BPS and BPF likely act through different mechanisms.

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Effects of BPA, BPS, and BPF on Oxidative Stress and Antioxidant Enzyme Expression in Bovine Oocytes and Spermatozoa

BPA and its analogs increase oxidative stress levels in in vitro cultured granulosa cells by altering anti-oxidant enzymes expression

Communications are crucial to ovarian follicle development and to ovulation, and while both folliculogenesis and oogenesis are distinct processes, they share highly interdependent signaling pathways. Signals from distant organs such as the brain must be processed and compartments within the follicle have to be synchronized. The hypothalamic-pituitary-gonadal (HPG) axis relies on long-distance signalling analogous to wireless communication by which data is disseminated in the environment and cells equipped with the appropriate receptors receive and interpret the messages. In contrast, direct cell-to-cell transfer of molecules is a very targeted, short distance messaging system. Numerous signalling pathways have been identified and proven to be essential for the production of a developmentally competent egg. The development of the cumulus-oocyte complex relies largely on short distance communications or direct transfer type via extensions of corona radiata cells through the zona pellucida. The type of information transmitted through these transzonal projections is still largely uncharacterized. This review provides an overview of current understanding of the mechanisms by which the gamete receives and transmits information within the follicle. Moreover, it highlights the fact that in addition to the well-known systemic long-distance based communications from the HPG axis, these mechanisms acting more locally should also be considered as important targets for controlling/optimizing oocyte quality. 

/pdf/mammalian-cumulus-oocyte-complex-communication-a-dialog-rtae0ojr.pdf

Mammalian cumulus-oocyte complex communication: a dialog through long and short distance messaging

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.

The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization

We evaluated metabolic profiles between cumulus cells (CCs) and mural granulosa cells (MGCs) derived from women with endometriosis to identify their correlations with oocyte quality. CCs and MGCs were collected from women with and without endometriosis undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. The metabolomics of CCs and MGCs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) followed by a quantitative polymerase chain reaction to further confirm the genes involved in the metabolic results. LC-MS/MS analysis revealed differences in 24 metabolites of CCs and 71 metabolites of MGCs between groups. Among them, five metabolites were upregulated and 19 metabolites were downregulated in CCs with endometriosis, whereas three metabolites were upregulated and 68 metabolites were downregulated in MGCs with endometriosis. Metabolites related to sphingolipid metabolism, which included palmitic acid (PA) and docosahexaenoic acid, increased significantly only in CCs with endometriosis, whereas sphingosine and PA were significantly downregulated in MGCs with endometriosis compared with CCs and MGCs without endometriosis. Gene expression involved in ceramide synthesis (CERS1, SPTL1, and SMPD1) and autophagy (BECN1, LAMP, and PC3) were significantly higher in CCs with endometriosis according to FASN, BECN1, and LAMP protein expressions. However, gene expression involved in ceramide synthesis (SPHK1, ASAH1, and SGPP1) and autophagy (BECN1, LAMP, and PC3) were significantly lower in MGCs with endometriosis, whereas CERS1 and UGCG expression increased. There are differences in sphingolipid metabolites in CCs and MGCs with endometriosis compared with women without endometriosis. These differences seem to be involved in the regulation of autophagic cell death in preovulatory follicles.

Er-Meng Gao

Papers

The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization

Dysregulated sphingolipid metabolism and autophagy in granulosa cells of women with endometriosis

Role of pyroglutamic acid in cumulus cells of women with polycystic ovary syndrome

Efficient silencing of the multicopy DUX4 gene by ABE-mediated start codon mutation in human embryos.