The impact of congenital uterine abnormalities on pregnancy and fertility: a literature review.

Congenital abnormalities of the uterus result primarily from embryological maldevelopment of the paramesonephric ducts and have been associated with pregnancy complications, reduced fertility, and other adverse fetal outcomes. While such abnormalities are rare, affected patients should be correctly managed to improve psychological, sexual, and reproductive outcomes. This review intends to elucidate the impact of congenital uterine abnormalities on fertility and pregnancy outcomes. We also present the available management methods and discuss the role of assisted reproductive technologies (ART) to benefit affected women. This review clearly shows that although these disorders are generally not lethal, they critically impact the patient's reproductive health. The fertility rate of patients with uterine congenital abnormalities depends on the severity of the condition. Reproductive endocrinologists and infertility specialists must be considered as active parts of the interdisciplinary treatment team for such patients. ART practices are reasonably successful at managing fertility problems of women with these abnormalities.

Disorders of sex development and female reproductive capacity: A literature review.

Disorders of sex development (DSD) are a wide-ranging group of complex conditions that influence chromosomal, gonadal, and phenotypic sex. The prevalence of DSD is very low, but affected patients deserve individualized management to improve psychological, sexual, and reproductive outcomes. This review aims to clarify the fertility potential of DSD patients who can be reared as females and their chance of becoming pregnant, especially using assisted reproductive techniques (ART). Due to the effects of DSD on internal and external genital organs, these conditions result in varying degrees of fertility potential. Fertility rate depends on the phenotype and is inversely related to the severity of the disorder. Reproductive endocrinologists and infertility specialists must be considered active partners of the interdisciplinary treatment team. With current advances in ART, pregnancy is more achievable in patients who were considered infertile at first glance. Due to the complexity of the medical management in DSD patients, more studies should be conducted to conclusively suggest the best choice for improving their fertility potential.Abbreviations: AIS: Androgen Insensitivity Syndrome; AMH: Anti-Müllerian Hormone; ART: Assisted Reproductive Technology; ASRM: American Society for Reproductive Medicine; CAH: Congenital Adrenal Hyperplasia; CAIS: Complete Androgen Insensitivity Syndrome; DHT: Dihydrotestosterone; DSD: Disorders of Sexual Development; FSH: Follicle Stimulating Hormone; GD: Gonadal Dysgenesis; ICSI: Intracytoplasmic Sperm Injection; IUGR: Intrauterine Growth Restriction; IVF: In Vitro Fertilization; IVF-ET: IVF and Embryo Transfer; LH: Luteinizing Hormone; MGD: Mixed Gonadal Dysgenesis; MRI: Magnetic Resonance Imaging; MRKH: Mayer-Rokitansky-Kuster-Hauser; US: Ultrasonography; HSG: Hysterosalpingography; PAIS: Partial Androgen Insensitivity Syndrome; PGD: Preimplantation Genetic Diagnosis; POR: P450 Oxidoreductase; PROM: Premature Rupture of Membranes; TS: Turner Syndrome; 17ß-HSD III: 17ß-Hydroxysteroid Dehydrogenase III; 21-OHD: 21-hydroxylase deficiency; 5α-RD-2: 5α-reductase-2.

Vitamin D3 protects against lead-induced testicular toxicity by modulating Nrf2 and NF-κB genes expression in rat.

Lead (Pb) is an environmental toxin that has the ability to alter biological processes by inducing oxidative stress (OS) and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) are two transcriptional factors that participate in the regulation of cellular responses against OS and inflammation. This study was conducted to evaluate the effects of vitamin D3 (VD) on the prevention of testicular damages of Pb and its association with Nrf2 and NF-κB gene expression levels and their downstream molecules. Forty male Wistar rats were divided into four groups and treatments were performed as following for four weeks: control group received no treatment, VD group were injected intramuscularly with 1000 IU of VD/Kg every other day, Pb group received 1000 mg of Pb/L of drinking water, and Pb + VD group were exposed to Pb and VD simultaneously. The results demonstrated significant decrease in the levels of tissue antioxidants, and increase in inflammatory cytokines in the Pb-intoxicated group, with increased Nrf2 and NF-κB mRNA levels. A remarkable reduction in sperm criteria and a significant disruption in serum hormones were also observed. Anyhow, VD supplementation during exposure to Pb showed a significant protective effect against all pathophysiologic alterations caused by Pb. Furthermore, VD affected the expression of Nrf2 and NF-κB and mitigated the harsh effects of Pb. In conclusion, our findings indicate that VD attenuated the toxic impacts of Pb on testis through modulation of Nrf2 and NF-κB gene expression levels which further regulated the OS and inflammatory responses.

Protective Effect of Vitamin D3 Against Pb-Induced Neurotoxicity by Regulating the Nrf2 and NF-κB Pathways.

Lead (Pb) is a known toxic heavy metal which accumulates in different tissues and causes oxidative stress (OS) and inflammation. The brain tissue is considered as one of the most vulnerable organs to the Pb-induced toxicity. The aim of this study was to investigate the therapeutic effects of vitamin D3 (VD) supplementation against the damages caused by chronic Pb toxicity in the cerebral cortex. Forty Wistar rats were divided into four equal groups and were treated as follows: control group received no treatment, VD group received 1000 IU/kg of VD by intramuscular injection every other day, Pb group received 1000 mg/L of Pb in drinking water, and Pb + VD group received VD and Pb simultaneously. The experiment lasted for 4 weeks and the analyses were conducted 24 h after the last administrations. The obtained results demonstrated that Pb significantly increased cortical lipid peroxidation and reactive oxygen species (ROS) levels. At the same time, there was a significant reduction in glutathione (GSH) content, catalase (CAT), and superoxide dismutase (SOD) activities, as well as a significant increase in the tissue level of inflammatory cytokines. Furthermore, Pb increased the messenger RNA (mRNA) expression level of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB). Anyhow, VD administration during the period of Pb exposure suppressed the OS and inflammation by increasing the antioxidant molecules and decreasing the inflammatory cytokines and consequently repaired Pb-induced cortical tissue damages. Remarkably, these responses were concomitant with the alterations in Nrf2 and NF-κB gene expressions. In conclusion, the present study discloses the potential protective effects for VD against Pb-induced neurotoxicity via anti-inflammatory and antioxidative mechanisms.