Pyridoxamine protects human granulosa cells against advanced glycation end-products-induced steroidogenesis disturbances.

BACKGROUND: Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM). METHODS AND RESULTS: Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3ß-HSD, and 17ß-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression. CONCLUSION: This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction.

Thymoquinone improves folliculogenesis, sexual hormones, gene expression of apoptotic markers and antioxidant enzymes in polycystic ovary syndrome rat model.

BACKGROUND: Nowadays, polycystic ovary syndrome (PCOS) is a prevalent cause of infertility affecting women of reproductive age around the world. Thymoquinone is a natural antioxidant, derived from Nigella sativa. OBJECTIVES: The current study aimed to evaluate the protective effects of thymoquinone on the detrimental effects of PCOS rats induced with letrozole. METHODS: Thirty-two female rats were randomly divided into four groups: (1) Control, (2) PCOS, (3) PCOS+5 mg/kg thymoquinone and (4) PCOS+10 mg/kg thymoquinone. Thymoquinone was administered every 3 days for 30 days. Ovaries were histopathologically and stereologically examined, and antioxidant and apoptotic enzymes gene expression in ovaries and sex hormones in serum were measured. RESULTS: The number of unilaminar, multilaminar, antral, and graffian follicles, volume density of corpus luteum (p < 0.01), and GPx1 gene expression in ovaries and level of FSH in the blood increased in both thymoquinone groups when compared to untreated PCOS (p < 0.05). Ovaries in thymoquinone groups showed a significant reduction in the number of atretic follicles, ovary weight and volume, volume density of cortex and ovarian cysts, Bax gene expression (p < 0.01) and Bax/Bcl2 ratio as well as levels of luteinizing hormone (LH), LH/FSH ratio and testosterone (p < 0.05) in the blood of female rats when compared to PCOS group. Administration of thymoquinone restored the most detrimental effects of PCOS on ovaries (p < 0.01) and sexual hormones (p < 0.05) in rats. CONCLUSIONS: These data suggest that thymoquinone has improved effects on ovarian function in the PCOS rat model. Therefore, thymoquinone might be useful as a protective agent and adjunct treatment in PCOS patients.

Effect of 1,25(OH)2-vitamin D3 on decidualization of human endometrial stromal cells.

Decidualization is the differentiation of endometrial stromal cells (eSC) to rounded, epithelioid-like cells during menstrual cycle and pregnancy. The impairment of this process leads to infertility and a variety of pregnancy disorders, including recurrent miscarriages and uteroplacental disorders. The aim of this study was to evaluate the effect of 1,25(OH)2-vitamin D3 (VD) on transformation of primary eSC into decidual cells. After isolation of eSC from biopsy samples of healthy fertile women and their characterization, the cells were cultured and propagated, and confluent cultures were decidualized for 12 days with progesterone (P4) and estradiol (E2) in presence or absence of VD. Prolactin (PRL) concentration was measured every 48 h in culture medium of eSCs, and ultrastructural changes were evaluated at the end of treatment. The results showed that PRL concentration in culture medium of eSCs was significantly increased in VD-treated decidual cells compared to control groups in a time-dependent manner. Ultrastructural analysis demonstrated that VD enhances many of the ultrastructural changes of decidualized cells including expansion of rough endoplasmic reticulum (rER), increased lipid droplets and high number of euchromatin round nuclei. These results suggest that VD may play an important role during early pregnancy by promoting cellular transformation associated with decidualization.

Effects of moderate COVID-19 infection on semen oxidative status and parameters 14 and 120 days after diagnosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing coronavirus disease 2019 (COVID-19). Because COVID-19 is a multisystem infection, there are some concerns regarding its possible effects on male fertility. This study aimed to investigate the effects of COVID-19 on semen oxidative status and parameters 14 and 120 days after diagnosis in patients presenting with moderate infection (defined as respiratory symptoms, with or without fever, with Spo2 <93% and >90% and lung involvement <50%). Semen samples were obtained from 20 participants at two time points: the first sample on Day 14 and the second on Day 120 after diagnosis. Semen parameters (sperm concentration, motility, morphology, and viability) were evaluated, as were levels of seminal reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC) and sperm DNA fragmentation. Semen parameters, including sperm motility and DNA integrity, improved at 120 days after the COVID-19 diagnosis relative to values at 14 days. In addition, ROS and MDA levels were significantly reduced in patients 120 days after infection, and TAC increased at 120 days compared with 14 days (during the acute stage of infection). In conclusion, the present study shows that the detrimental effects of COVID-19 on sperm properties caused by oxidative stress decrease up to Day 120 after diagnosis.

Endometrial expression of ß3 integrin, calcitonin and plexin-B1 in the window of implantation in women with unexplained infertility.

BACKGROUND: Endometrial receptivity plays a key role in the establishment of successful implantation and its impairment may contribute to subfertility and limit the assisted reproduction techniques (ART) success. OBJECTIVE: The aim of present study was to investigate endometrial receptivity in terms of ß3 integrin, calcitonin and plexin-B1 expression in women with unexplained infertility. MATERIALS AND METHODS: We evaluated expression of ß3 integrin, calcitonin and plexin-B1 through mRNA level measurement with real-time RT-PCR, in the endometrium of 16 infertile women with unexplained infertility and 10 fertile women. Endometrial biopsies were collected during a single menstrual cycle on postovulatory day LH+7 in each subject. RESULTS: Significant differences regarding ß3 integrin and calcitonin expression levels found between patients with unexplained infertility and the fertile women. Endometrial plexin-B1 expression levels showed no significant difference between fertile and infertile women. There were significant correlations between expression of ß3 integrin with calcitonin and plexin-B1 in fertile and infertile women. CONCLUSION: Reduced in endometrial expression of ß3 integrin and calcitonin alone or together may contribute to unexplained infertility and these genes could account as the potential molecular markers of infertility.