Testicular germ cell tumor (TGCT) incidence and related characterization in 129.MOLF-L1 congenic mice with or without <i>in utero</i> flutamide, DES, or radiation treatment.

a<p>Mean ± SEM.</p>b<p>Values given as absolute number and percentage of mice, testes, or tumors analyzed.</p>c<p>Since the incidence of tumors in the DES-treated mice was not increased from historical controls or the concurrent flutamide controls, we did not complete this arm of the study, and cannot rigorously conclude that there is no increase in tumor incidence in DES-treated mice compared to a sham-treated control group.</p>d<p>Two cryptorchid testes (weights, 19 and 34 mg) were excluded from this average.</p>e<p>Significantly different between treated and control mice, Fisher's exact Chi square test: <i>P</i><0.01. Other differences were not significant (<i>P</i>≥0.05).</p>f<p>Significantly different between treated and control mice, <i>t</i> test: <i>P</i><0.01. Other differences were not significant (<i>P</i>≥0.05).</p

Breeding efficiency in 129.MOLF-L1 congenic mice with or without <i>in utero</i> flutamide, DES, or radiation treatment.

a<p>Values given as absolute number and percentage of total plug-positive females.</p>b<p>Mean ± SEM.</p

Morphology and histology of the testes in 4-week-old 129.MOLF-L1 male mice irradiated <i>in utero</i> with two doses of 0.8 Gy and controls.

<p>Testicular morphology showing bilateral (<b>A</b>) and unilateral (<b>B</b>) TGCTs from irradiated mice. Note that the testis without TGCT after <i>in utero</i> radiation exposure (B) is smaller than the normal untreated testis from a 4-week-old mouse (insert in B). Testis sections showing teratoma containing tissues apparently from multiple dermal origins identified by morphology (<b>C</b>), and TGCT containing only neuroepithelial cells (NE) (<b>D</b>). CA: cartilage; BM: bone marrow; MS: muscle, EEP: endodermal epithelium. ST: seminiferous tubule; BV: blood vessel. Sections from testes of 4-week old irradiated (<b>E</b>) and contol (<b>F</b>) mice without TGCT showing qualitatively normal spermatogenesis. Bar: 0.5 cm in A & B, and 50 µm in C–F.</p

Increased testicular germ cell tumor incidence (TGCT) in 129 and L1 mice exposed <i>in utero</i> to cyclophosphamide (CP) or radiation.

a<p>Values given as absolute number and percentage of mice, testes, or tumors analyzed.</p>b<p>Data from 129S5 and 129S1/SvImJ mice were pooled.</p>c<p>Significantly different between treated and control mice (<i>P</i><0.05; Fisher's exact test).</p>d<p>Significantly different between CP-exposed and irradiated mice of the same strain (<i>P</i><0.05; Fisher's exact test).</p>e<p>The odd number is due to the presence of only one testis in one of the mice analyzed, which was not considered for bilateral TGCT analysis.</p>f<p>Significantly different between treated and control mice (<i>P</i><0.05; <i>t</i> test).</p>g<p>Data from a previous study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093311#pone.0093311-Shetty1" target="_blank">[5]</a> were included for comparison.</p

Reduction of testis weights and sperm counts in 8-week-old 129S1/SvImJ mice exposed to cyclophosphamide (CP) <i>in utero</i>.

a<p>Significantly different between treated and control mice (<i>P</i><0.01; <i>t</i>-test).</p

Effect of cyclophosphamide (CP) or radiation on days 10.5 and 11.5 after mating on breeding efficiency of 129 and L1 mice.

<p>Abbreviation: ND, no data.</p>a<p>Values given as absolute number and percentage of total vaginal plug-positive females.</p>b<p>The number of male offspring per group ranged from 19 to 51.</p>c<p>Data from 129S5 and 129S1/SvImJ mice were pooled.</p>d<p>Significantly different between treated and control mice (<i>P</i><0.05; Fisher's exact test).</p>e<p>Significantly different between treated and control mice (<i>P</i><0.05; <i>t</i> test).</p>f<p>Historical data from previous study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093311#pone.0093311-Shetty1" target="_blank">[5]</a> were used for comparison.</p

Histology of testes and ovaries from 129 mice exposed to cyclophosphamide at 7.5 mg/kg/day on E10.5 and 11.5.

<p>(A-D) Testes from 4-week-old mice. (A) TGCT characterized as a teratoma originating from multiple dermal layers; (B) TGCT containing only neuroepithelial cells. Abbreviations: BM: bone marrow; CA: cartilage; EEP: endodermal epithelium; NE: neuroepithelial cells; MS: muscle; ST: seminiferous tubule. (C) non-TGCT-bearing testis showing active and atrophic tubules. (D) High magnification of atrophic tubules containing only Sertoli cells. (E-H) Ovaries from 7-day-old mice. (E, G) From a mouse treated on E10.5 and 11.5 with 7.5 mg CP/kg/day. (F, H) Control ovary of the same age. G and H are the magnified views from portions of E and F respectively, showing primordial (PO), primary-transitional (PT) and primary (PR) follicles. The bar represents 100 μm in A, B, C, E & F; 30 μm in D; 10 μm in G and H.</p