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Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used in manufacturing. Previous studies have shown that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of DEHP, has inhibitory effects on luteinizing hormone (LH)-stimulated steroid biosynthesis by Leydig cells. The molecular mechanisms underlying its effects, however, remain unclear. In the present study, we examined the effects of MEHP on changes in mitochondrial function in relationship to reduced progesterone formation by MA-10 mouse tumor Leydig cells. Treatment of MA-10 cells with MEHP (0-300 μM for 24 h) resulted in dose-dependent inhibition of LH-stimulated progesterone biosynthesis. Biochemical analysis data revealed that the levels of the mature steroidogenic acute regulatory protein (STAR), a protein that works at the outer mitochondrial membrane to facilitate the translocation of cholesterol for steroid formation, was significantly reduced in response to MEHP exposures. MEHP also caused reductions in MA-10 cell mitochondrial membrane potential (ΔΨm) and mitochondrial respiration as evidenced by decreases in the ability of the mitochondria to consume molecular oxygen. Additionally, significant increases in the generation of mitochondrial superoxide were observed. Taken together, these results indicate that MEHP inhibits steroid formation in MA-10 cells at least in part by its effects on mitochondrial function., (Copyright © 2021. Published by Elsevier B.V.)

The severity of influenza increases with age, with worse disease in aged males than females. Testosterone concentrations decline with age in males, which may impact influenza pathogenesis. Aged male mice were treated with testosterone or placebo and outcomes during influenza A virus (IAV) infection were compared with adult male mice. Aged males experienced greater morbidity and mortality than adult males, which was partially improved by testosterone treatment of aged males. Aged males cleared IAV from lungs slower than adult males, regardless of testosterone treatment. As compared with adult males, aged males experienced pulmonary, but not systemic, cytokine dysregulation, and delayed influx and contraction of IAV-specific CD8 + T cells in the lungs. Testosterone treatment in aged males partially restored pulmonary cytokine responses to levels consistent with adult males but did not alter the age-associated changes in IAV-specific CD8 + T cells. Testosterone only modestly improves outcomes of influenza in aged males., (Copyright © 2019 Elsevier Inc. All rights reserved.)

These studies were designed to test the hypothesis that sperm nuclear decondensation and male pronuclear formation during hamster fertilization depend upon the ability of the fertilized oocyte to reduce sperm nuclear disulfide bonds. In a first series of experiments, treatment of mature oocytes with the sulfhydryl blocking agent iodoacetamide or the glutathione oxidant diamide caused a dose-dependent inhibition of decondensation in microinjected sperm nuclei. Inhibition of decondensation was not observed, however, when sperm nuclei were treated in vitro with dithiothreitol (DTT) to reduce disulfide bonds prior to their microinjection. In a second series of experiments, germinal vesicle (GV)-intact oocytes and pronuclear eggs, in which mature, disulfide-rich sperm nuclei do not decondense, were found to support the decondensation of disulfide-poor DTT-treated sperm nuclei or testicular spermatid nuclei. The decondensed sperm nuclei were not, however, transformed into male pronuclei. The results of these studies suggest: (1) that sperm nuclear decondensation in the hamster requires disulfide bond reduction, (2) that GV-intact oocytes and pronuclear eggs lack sufficient reducing power to effect sperm nuclear decondensation, and (3) that disulfide bond reduction is required but not sufficient for pronuclear formation.

Estradiol deprivation in vivo causes accumulation of cholesterol and cholesterol ester in the corpora lutea of pseudo-pregnant rabbits within 24 hours. These accumulations occur concomitantly with an abrupt cessation of progestin production. Retreatment with estradiol restores progestin production and can block further increases in cholesterol accumulation (per mg total tissue protein). Ample quantities of precursor cholesterol ester and cholesterol substrate are present in corpora lutea when progestin falls because of estradiol deprivation. We conclude therefore that the gonadotropic action of estradiol is, in part, because of its stimulation of cholesterol conversion to progestins.