Germline-dependent transmission of male reproductive traits induced by an endocrine disruptor, di-2-ethylhexyl phthalate, in future generations

Abstract

in males, defective reproductive traits induced by an exposure to an endocrine disruptor are transmitted to future generations via epigenetic modification of the germ cells. Interestingly, the impacted future generations display a wide range of heterogeneity in their reproductive traits. in this study, the role that the Y chromosome plays in creating such heterogeneity is explored by testing the hypothesis that the Y chromosome serves as a carrier of the exposure impact to future generations. this hypothesis implies that a male who has a Y chromosome that is from a male that was exposed to an endocrine disruptor will display a more severe reproductive phenotype than a male whose Y chromosome is from an unexposed male. To test this hypothesis, we used a mouse model in which F1 generation animals were exposed prenatally to an endocrine disruptor, di-2-ethylhexyl phthalate (DEHP), and the severity of impacted reproductive traits was compared between the F3 generation males that were descendants of F1 males (paternal lineage) and those from F1 females (maternal lineage). Pregnant dams (F0 generation) were exposed to the vehicle or 20 or 200 μg/kg/day of DEHP from gestation day 11 until birth. Paternal lineage F3 DEHP males exhibited decreased fertility, testicular steroidogenic capacity, and spermatogenesis that were more severely impaired than those of maternal lineage males. indeed, testicular transcriptome analysis found that a number of Y chromosomal genes had altered expression patterns in the paternal lineage males. This transgenerational difference in the DEHP impact can be attributed specifically to the Y chromosome.

Evaluation of sex steroid hormones and reproductive irregularities in diethyl phthalate-exposed premature mice: modulatory effect of raw honey against potential anomalies

“…However, the length was similar to the control group. Several other researchers reported decreased gonadal size (Barakat et al, 2020). Where male mice were prenatally exposed with DEP mixture in 20 µg/kg and 500 mg/kg showed decreased gonadal weight in a dose-dependent way.…”

Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

“…Many other compounds reported to affect the methylation pattern in offspring are mentioned in Table 2. ↑Cdyl; ↑Zfy2) [141] (DEHP in mixture with genistein) Rat 0.1 and 10 mg/kg/day Kitlg, Rsk2, Nr3c1, Nqo1, Lif, Fyn, Dep-1, Gpr116, Pfn2 and Ptgr1 [142] Other EDCs, such as pesticides, can also cause differential methylation signatures in the coming generations, hence increasing the susceptibility to disease not only in the exposed individuals but also in the next generations through epigenetic inheritance. One such chemical is methoxychlor, which has been shown to cause epimutations in sperm that can then be transferred to the offspring resulting in ovarian defects and obesity in females, primarily caused by differentially methylated regions caused by methoxychlor in the parents [143].…”

Isolation of Phthalates and Terephthalates from Plant Material – Natural Products or Contaminants?

“…This is because of a growing disquiet that phthalates can have harmful effects. DEHP (9) has been found to be an endocrine disruptor [23] and possible carcinogen [24], and DINP (15) has also been put on the list of possible carcinogens [25] by the California Office of Environmental Health Hazard Assessment (OEHHA) in 2013. In fact, butyl benzyl phthalate (BBzP, 1), dibutyl phthalate (DnBP, 5), diethyl phthalate (DEP, 7), diisobutyl phthalate (DiBP, 12), diisononyl phthalate (DINP, 15), di-n-octyl phthalate (DnOP, 20), dipentyl phthalate (DNPP, 9), di-isohexyl phthalate, dicyclohexyl phthalate (DcHP, 11), and di-isoheptyl phthalate have all been associated with illnesses and disorders as diverse as attention-deficit hyperactivity disorder [26], breast cancer [27], obesity [28] and type II diabetes [29], neurodevelopmental issues [30], behavioral issues, autism spectrum disorders [31], altered reproductive development [32] and male fertility issues [33].…”

“…The structure presented in the paper is that of the meso form of the compound, (R/S)-bis(2methylheptyl) phthalate ( 36) [129], but the isolation of the compound could potentially be that of a mixture of stereoisomers. Different is the case of the isolation of bis(2Smethylheptyl) phthalate from Galinsoga parviflora, a herbaceous plant of the Asteraceae family, where the isolated compound shows a specific optical rotation [α] D 23 of 193.5° (c = 0.075M, MeOH). Here, the question remains as to whether selective enzymatic hydrolysis of a mixture of bis(2methylheptyl) phthalate stereoisomers has led to (R/S)-bis(2methylheptyl) phthalate (36) as the one remaining dialkyl phthalate or whether the phthalate as a whole has been biosynthetically created (Fig.…”