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Di (2-ethylhexyl) phthalate (DEHP) is widespread in the environment. It can impair sperm function through damaging the sperm development process. However, few studies have focused on the sperm tail that is directly related to sperm motility. In this study, we demonstrate that DEHP impedes the conversion of riboflavin in the mitochondrial sheath in the midsection of the sperm tail, resulting in reduced ATP (adenosine triphosphate) synthesis, thereby inhibiting sperm motility. The results of HPLC-MS/MS showed that DEHP metabolites were transported to the testes and epididium, indicating that MEHP (Mono-2-ethylexyl phthalate) could directly affect the espermatozoa of mature. Sperm motility analysis determined that sperm motility decreased with increasing DEHP concentration. The movement of sperm is mainly dependent on the tail motility, which is largely determined by tail structure and energy supply. Electron microscopy images illustrate that there are no observable changes in the basic kinematic structure of the sperm tail. However, DEHP causes a decrease in complex II activity of mitochondrial respiratory chain by interfering with the synthesis of the cofactor FAD (Flavin adenine dinucleotide), which leads to a decrease in ATP concentration. Therefore, DEHP exposure can reduce sperm motility by decreasing sperm tail energy supply. This study exemplifies the importance of the sperm tail in sperm dysfunction caused by environmental pollutants.

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 μg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.

Our previous study showed 1-Nitropyrene (1-NP) exposure disrupted testicular testosterone synthesis in mouse, but the exact mechanism needs further investigation. The present research found 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum (ER) stress inhibitor, recovered 1-NP-induced ER stress and testosterone synthases reduction in TM3 cells. GSK2606414, a protein kinase-like ER kinase (PERK) kinase inhibitor, attenuated 1-NP-induced PERK-eukaryotic translation initiation factor 2α (eIF2α) signaling activation and downregulation of steroidogenic proteins in TM3 cells. Both 4-PBA and GSK2606414 attenuated 1-NP-induced steroidogenesis disruption in TM3 cells. Further studies used N-Acetyl-L-cysteine (NAC) as a classical antioxidant to explore whether oxidative stress-activated ER stress mediated 1-NP-induced testosterone synthases reduction and steroidogenesis disruption in TM3 cells and mouse testes. The results showed NAC pretreatment mitigated oxidative stress, and subsequently attenuated ER stress, particularly PERK-eIF2α signaling activation, and downregulation of testosterone synthases in 1-NP-treated TM3 cells. More importantly, NAC extenuated 1-NP-induced testosterone synthesis in vitro and in vivo. The current work indicated that oxidative stress-caused ER stress, particularly PERK-eIF2α pathway activation, mediates 1-NP-downregulated steroidogenic proteins and steroidogenesis disruption in TM3 cells and mouse testes. Significantly, the current study provides a theoretical basis and demonstrates the experimental evidence for the potential application of antioxidant, such as NAC, in public health prevention, particularly in 1-NP-induced endocrine disorder.

Di (2-ethyl-hexyl) phthalate (DEHP) is a wildly used plasticizer. Maternal exposure to DEHP during pregnancy blocks the placental cell cycle at the G2/M phase by reducing the efficiency of the DNA repair pathways and affects the health of offsprings. However, the mechanism by which DEHP inhibits the repair of DNA damage remains unclear. In this study, we demonstrated that DEHP inhibits DNA damage repair by reducing the activity of the DNA repair factor recruitment molecule PARP1. NAD+ and ATP are two substrates necessary for PARP1 activity. DEHP abated NAD+ in the nucleus by reducing the level of NAD+ synthase NMNAT1 and elevated NAD+ in the mitochondrial by promoting synthesis. Furthermore, DEHP destroyed the mitochondrial respiratory chain, affected the structure and quantity of mitochondria, and decreased ATP production. Therefore, DEHP inhibits PARP1 activity by reducing the amount of NAD+ and ATP, which hinders the DNA damage repair pathways. The supplement of NAD+ precursor NAM can partially rescue the DNA and mitochondria damage. It provides a new idea for the prevention of health problems of offsprings caused by DEHP injury to the placenta.

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amniotic fluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3β-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placental trophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.

Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China, where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification, and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone, oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of "depositional fabricselithologyemicrofacies", an association between a fore mound, mound framework, and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions (TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound, exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions (TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain lateral comparison profile and seismic reflection structures in the 2D seismic section, which can provide references for future worldwide exploration. Microbial mounds with larger buildups and thicker vertical reservoirs are typically targeted on the windward margin, while small-sized microbial mounds and flats with better lateral connections are typically focused on the leeward margin. [ABSTRACT FROM AUTHOR]

The article discusses research which aimed to investigate the gestational exposure of mice to human-relevant doses of perfluorohexane sulfonate (PFHxS). Cited are the integrity and quantity of messenger RNA (mRNA) that are essential in placental function and fetal development which was measured using a combination of alternative splicing and genome-wide expression analyses, and epidemiological findings regarding the associations of PFHxS with lower birth weight.