Prenatal exposure to benzo[a]pyrene depletes ovarian reserve and masculinizes embryonic ovarian germ cell transcriptome transgenerationally.

People are widely exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP). Prior studies showed that prenatal exposure to BaP depletes germ cells in ovaries, causing earlier onset of ovarian senescence post-natally; developing testes were affected at higher doses than ovaries. Our primary objective was to determine if prenatal BaP exposure results in transgenerational effects on ovaries and testes. We orally dosed pregnant germ cell-specific EGFP-expressing mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cells at E13.5 and follicle numbers at postnatal day 21 were significantly decreased in F3 females at all doses of BaP; testicular germ cell numbers were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Next, we compared the ovarian effects of 2 mg/kg-day BaP dosing to wild type C57BL/6J F0 dams from E6.5-11.5 or E12.5-17.5. We observed no effects on F3 ovarian follicle numbers with either of the shorter dosing windows. Our results demonstrate that F0 BaP exposure from E6.5-15.5 decreased the number of and partially disrupted transcriptomic sexual identity of female germ cells transgenerationally.

Outcome of Architectural Distortion Detected Only at Breast Tomosynthesis versus 2D Mammography.

Purpose To compare the outcome of architectural distortion (AD) without associated mass only on digital breast tomosynthesis (DBT) with AD seen at two-dimensional (2D) mammography and to evaluate if the incidence of malignancy is influenced by the presence of a correlate at ultrasonography (US). Materials and Methods This retrospective study had institutional review board approval and was HIPAA compliant. All consecutive cases in which patients with AD were ultimately assigned Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 categories from 2009 to 2016 were reviewed by three readers for visibility (2D vs DBT). The level of suspicion was assigned using a Likert scale. Pathologic results were compared between 2D-detected and DBT-detected AD. Frequencies were compared by using the McNemar and Pearson χ2 exact tests. Results One hundred eighty-one AD lesions were included; 122 (67.4%) were 2D visible while 59 (32.6%) were DBT detected. Forty-two women (with 43 lesions) underwent 2D mammography prior to initiation of DBT. In 117 women with 121 AD lesions who underwent 2D mammography plus DBT, 59 lesions (48.8%) were detected only with DBT. The malignancy rate based on final pathology was significantly higher for 2D-detected AD (53 [43.4%] of 122) compared with DBT (six [10.2%] of 59) (P < .001). A US correlate was more frequent with 2D-detected AD (103 [84.4%] of 122) than DBT (33 [55.9%] of 59) (P < .001). Malignancy rate was not different for DBT-detected AD with (four [12.1%] of 33; 95% confidence interval [CI]: 3.4%, 28.2%]) or without (two [7.7%] of 26; 95% CI: 0.9%, 25.1%]) a US correlate. NPV based on radiologists' level of suspicion was high (91.8%-98.0%) but not sufficient enough to forgo biopsy. Conclusion DBT-detected suspicious AD has a lower malignancy outcome compared with 2D mammography-detected suspicious AD, although still high enough to warrant biopsy. © RSNA, 2018 Online supplemental material is available for this article.