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1.
Toxicol Mech Methods ; 30(5): 336-349, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32166990

ABSTRACT

In cosmetics and food products, parabens are widely used as antimicrobial agents. Reports have suggested that parabens may be linked to infertility, owing to their effects on basal steroidogenesis properties or their capacity to inflict mitochondrial damage. Despite growing concerns about parabens as endocrine disruptors, it is unclear whether they affect any of these actions in humans, particularly at environmentally relevant concentrations. In this work, an in vitro primary culture of human granulosa cells was used to evaluate steroidogenesis, based on the assessment of progesterone production and regulation of critical steroidogenic genes: CYP11A1, HSD3B1, CYP19A1, and HSD17B1. The effects of two commercially relevant parabens, methylparaben (MPB) and butylparaben (BPB), were screened. Cells were exposed to multiple concentrations ranging from relatively low (typical environmental exposure) to relatively high. The effect was assessed by the parabens' ability to modify steroidogenic genes, progesterone or estradiol production, and on mitochondrial health, by evaluating mitochondrial activity as well as mtDNA content. Neither MPB nor BPB showed any effect over progesterone production or the expression of genes controlling steroid production. Only BPB affected the mitochondria, decreasing mtDNA content at supraphysiological concentrations (1000 nM). Prolonged exposure to these compounds produced no effects in neither of these parameters. In conclusion, neither MPB nor BPB significantly affected basal steroidogenesis in granulosa cells. Although evidence supporting paraben toxicity is prevalent, here we put forth evidence that suggests that parabens do not affect basal steroidogenesis in human granulosa cells.


Subject(s)
Endocrine Disruptors/toxicity , Granulosa Cells/drug effects , Parabens/toxicity , Progesterone/biosynthesis , Adult , Aromatase/genetics , Body Fluids/chemistry , Cells, Cultured , Cholesterol Side-Chain Cleavage Enzyme/genetics , DNA, Mitochondrial/metabolism , Dose-Response Relationship, Drug , Endocrine Disruptors/administration & dosage , Endocrine Disruptors/analysis , Estradiol Dehydrogenases/genetics , Female , Granulosa Cells/metabolism , Humans , Mitochondria/drug effects , Mitochondria/metabolism , Models, Biological , Multienzyme Complexes/genetics , Parabens/administration & dosage , Parabens/analysis , Primary Cell Culture , Progesterone Reductase/genetics , Steroid Isomerases/genetics
2.
Clin Transl Med ; 9(1): 14, 2020 Feb 07.
Article in English | MEDLINE | ID: mdl-32030567

ABSTRACT

BACKGROUND: At our facilities, patients that received embryos using donor oocyte during in vitro fertilization (IVF), usually have had at least one failed attempt to produce at least one euploid embryo with their own oocytes; however, the current debate between using donor over patient oocytes remains inconclusive. We examined the aneuploidy rate and IVF clinical outcomes from embryos derived from either donor or patient oocytes. METHODS: Retrospectively, 973 cycles were examined of patients who underwent a standard IVF protocol. Chromosomal content was determined using Pre-implantation Genetic Testing (PGT) by either microarray-comparative genomic hybridization or Next-generation sequencing from either Day 3 (blastocysts) or Day 5 (trophectoderm) embryo biopsies, respectively. Embryo implantation was confirmed by serum ß-hCG (> 10 m IU/mL/Day 14), whereas clinical pregnancy by a fetal heartbeat (Week 6.5-8). RESULTS: Embryos derived from donor oocytes presented with more monosomies than embryos derived from patient oocytes (41.2% vs. 25.4%, p < 0.05, respectively); however, only Trisomy 7 (0.4% vs. 2.3%, p < 0.05) and Trisomy in X (0.7% vs. 2.3%, p < 0.05) were significantly less present when compared to patient oocyte derived embryos. Interestingly, rates for embryo implantation (46.7% vs. 50.8%, p = 0.35), clinical pregnancy (38.5% vs. 43.1%, p = 0.30), and live birth (30.5% vs. 30.5%, p = 0.99) were similar for embryos derived from donor and patient oocytes. These results did not change when adjusted for the number of embryos implanted. CONCLUSION: Here, we show no significant differences in achieving pregnancy when using donor oocytes. Taking into consideration that aneuploidy rates are > 30% in embryos, independent of the oocyte origin, PGT should be recommended with donor oocytes as well.

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