Abstract
Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7d to 19d, experimental group was sustained to gavage DEHP 750mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat’s weight and AGD value, after maturation (PND80) recording testis and epididymis’ size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role in the development of imprinted genes imbalances, and eventually lead to producing offspring cryptorchidism. This may be an important mechanism of reproductive system damage.
Highlights
Epigenetic transgenerational inheritance involves the germline transmission of an altered epigenome and phenotypes across generations in the absence of direct environmental exposures [1]
Results show DEHP can lead to "acquired" children cryptorchidism inter-generational genetic phenomenon, with the increase of generations, offspring of male rats gradually reduce the incidence of cryptorchidism
DEHP induced offspring of male rat reproductive function damage inspection as shown in (Table 3), control males makes the conception of female was 100%, the ratio of DEHP processing makes the conception rate of 50% in F1, F2 generation was 75%, F3 and F4 generation were 100%
Summary
Epigenetic transgenerational inheritance involves the germline transmission of an altered epigenome and phenotypes across generations in the absence of direct environmental exposures [1]. A number of environmental chemical exposures have been shown to promote epigenetic transgenerational inheritance of cryptochidism and the transgenerational epigenetic changes may be used as biomarkers of exposure and disease[5]. This study was designed to investigate the potential that dioxin ((Di(2-Ethylhexyl) Phthalate, DEHP) promotes epigenetic transgenerational inheritance of cryptochidism. No human studies have investigated transgenerational (4 generations) effects of DEHP. Previous studies with DEHP used high dose(500 to 750mg/kg bw/day) and only evaluated the direct exposure of adult and fetus (F0 and F1) generations[10]. It was designed to investigate the potential that DEHP may promote transgenerational disease. Since the exposure of a gestating F0 generation female directly exposes the F1 generation fetus and germ line that will generate the F2 generation, F3 generation without direct exposure[11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
