Search

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor β (ERβ). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases. [Display omitted] • The results of clinical questionnaires reveal risk factors for hypospadias. • DEHP induces hypospadias through estrogenic and oxidative stress mechanisms. • GEN prevents hypospadias via anti-estrogenic and anti-oxidative stress effects. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study investigated changes in refraction, corneal curvature, axial components and weight of posterior sclera in guinea pig eyes during the normal development from birth. Methods: Sixty-four guinea pigs were assigned to eight groups (n =8 each). Each group underwent a series of ocular measurements at one of the eight time-points (0, 1, 2, 3, 5, 7, 9 and 11 weeks), including refraction (streak retinoscopy), corneal radius of curvature (CRC; keratometry), anterior segment length (AS: corneal thickness and depth of the anterior chamber), thickness of the crystalline lens (CL), vitreous chamber length (VC; all A-scan ultrasonography) and dry weight of a circular 6mm diameter punch in the posterior sclera (electronic balance). Results of all the measurements were statistically compared between right eye and left eye, male and female and among different age groups. Artifacts of retinoscopy due to small eye artifact were also estimated at different ages. Results: The refraction in guinea pig eyes was +5.22±0.23D (Mean, SE) at birth. This value decreased rapidly during the first 3 weeks followed by a slow decline. The overall decrease in refraction was highly significant from birth to 11 weeks (p <0.001 one way ANOVA). The small eye artifact was approximately 4.00D at birth, which reduced to 2.76D at 11 weeks. The guinea pig eyes were emmetropic by 3 weeks of age when the small eye artifact was taken into account. The CRC (3.24±0.01mm at birth), AS (1.20±0.01mm at birth), CL (2.72±0.03mm at birth) and VC (3.28±0.01mm at birth) increased within the first 3 weeks despite a transient decrease in the CRC within the first week. The increase in CRC, CL and VC continued after 3 weeks, however, the AS remained constant after this age. The increase in VC was better correlated to the decline of hyperopia (R 2 =0.70) than the other components (R 2 =0.33–0.39). Dry weight of the posterior sclera increased linearly from birth (p <0.001 between any two close time-points from 3 to 9 weeks) and had a moderately linear correlation with the VC (R 2 =0.60). There were no significant differences between the right eye and left eye or between male and female in all the measurements. Conclusions: In guinea pigs, the hyperopia present at birth rapidly reduces to emmetropia within the first 3 weeks of age. The emmetropization process in guinea pigs is mainly related to the increase in the vitreous chamber length. This relationship in guinea pigs is similar to that in chickens, tree shrews, primates and humans. The axial development of the vitreous chamber in guinea pigs appears to be associated with tissue growth of the posterior sclera. [Copyright &y& Elsevier]