Peri-ovulatory putrescine supplementation reduces embryo resorption in older mice

Tao, Yong; Liu, Dandan; Mo, Guolong; Wang, Hongmei; Liu, X. Johné

doi:10.1093/humrep/dev130

Cited by 19 publications

(28 citation statements)

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“…Older C57BL/6 mice (8–11 months of age) exhibit modest egg aneuploidy rates, 2.6%-12.7% [ 18 , 24 ]. Ten (10) month-old C57BL/6 mice however exhibit extraordinarily high level of early embryo death (60%) [ 25 ], implying that aneuploidy might not be the leading cause of embryo death in older mice.…”

Section: Resultsmentioning

confidence: 99%

“…To address this directly, we recovered all severely retarded ( Fig 1B ) and resorbed ( Fig 1C and 1D ) implants at 9.5 dpc from the 10-month-old C57BL/6 mice [ 25 ], and subjected them for karyotype analyses. To facilitate karyotype analyses, we further classified resorptions into two grades, with Grade 1 having some fetal tissues ( Fig 1C ) and Grade 2 with only remnants of ectoplacental cone ( Fig 1D ).…”

Section: Resultsmentioning

confidence: 99%

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The Majority of Resorptions in Old Mice Are Euploid

Tao

2015

PLoS ONE

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Chromosomal abnormality is a leading cause of aging-related infertility, spontaneous abortion and congenital birth defects in humans. Karyotype analyses of spontaneously aborted human fetuses reveal high proportions (~50%) being chromosomal abnormal with the majority being trisomies of various chromosomes. As a model organism, mice are widely used for studies of reproduction and reproductive aging. Like older women, older mice exhibit high incidences of early embryo death. However, it is not known if aneuploidy is prevalent amongst resorptions in older mice. We have karyotyped 65 retarded/resorbed fetuses in 10-month-old C57BL/6 mice, and found that 55 (84.6%±8.8%, with 95% confidence) were euploid. Similarly, of 40 such fetuses from 17 month-old C57BL/6 mice, we found 38 (95±7%, with 95% confidence 95%) being euploid. Therefore, aneuploidy is not a leading cause of embryo death in older mice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Majority of Resorptions in Old Mice Are Euploid

Tao

2015

PLoS ONE

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“…Compared with the control group, which exhibited evenly sized implantation sites, the mice exposed to 0.2 mg/kg BaP exhibited abnormal implantation sites, and those exposed to 2 mg/kg BaP displayed no trace of pregnancy ( Table 2 ). Since days 8-10 of gestation are a critical period for implantation and placentation [ 17 ], some mouse exposure to BaP was extended to day 10 of gestation. Mice exposed to 0.2 mg/kg BaP presented 7.5 normal fetuses and 2.5 resorption sites on average, and the resorption rate is 33.3%, while control mice presented no resorption site (Figures 1(b) and 1(c) ).…”

Section: Resultsmentioning

confidence: 99%

“…Morphological observations were performed independently by two persons who were blinded to the group assignment of the mice. Abortion: no pregnant sacs in pregnant mice, defined as emergence of vaginal plugs Resorption fetuses: implantation sites containing no intact fetus inside the placenta Abnormal fetuses: fetuses which appeared intact but were considerably smaller than their normal littermates or normal fetuses from other mice Resorptions: implantation sites containing no intact fetus inside the placenta Abortion rate: number of pregnant mice without implantation site/number of pregnant mice with vaginal plugs × 100% Percentage of abnormal fetuses: number of abnormal fetuses/total number of fetuses observed × 100% [ 17 ] …”

Section: Methodsmentioning

confidence: 99%

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Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

Yue

Jiang

Zhang

et al. 2020

BioMed Research International

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Objects. To investigate the effects of environmental pollutant benzo(a)pyrene (BaP) and its metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) on human trophoblasts and on murine miscarriages. Methods. The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women. Results. We observed a concentration-dependent incidence of abnormal murine fetuses, beginning with 0.1 mg/kg BaP; with a BaP concentration of 2 mg/kg, no fetuses developed. Correspondingly, a BPDE concentration-dependent apoptosis of human trophoblasts. Beginning with 0.5 μM BPDE exposure, Bax/Caspase-3 were increased and Bcl-2 decreased. Furthermore, BPDE also inhibited, in a dose-dependent manner, the migration of villous explants from elective abortion women, consistent with the reduced migration of villous explants from women with recurrent pregnancy loss (RPL), and reduced the cell immigration in Swan 71 trophoblasts, in a dose-dependent manner measured by transwell assays. Conclusions. Our study results provide mechanistic insight to the effect of BPDE on trophoblast dysfunction through enhanced cell apoptosis and inhibited migration, providing further experimental evidence to the causative links between BaP exposure and PRL.

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Targeting oocyte maturation to improve fertility in older women

2015

Cell Tissue Res

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Reproductive aging is an increasingly pressing problem facing women in modern society, due to delay in child bearing. According to Statistics Canada, 52% of all Canadian births in 2011 were by women aged 30 years and older, up from 24% in 1981 ( http://www.statcan.gc.ca/pub/91-209-x/2013001/article/11784-eng.htm ). Women older than 35 years of age experience significantly increased risks of infertility, miscarriage and congenital birth defects, mostly due to poor quality of the eggs. Increasingly sophisticated, and often invasive, assisted reproductive technologies (ARTs) have helped millions of women to achieve reproductive success. However, by and large, ARTs do not address the fundamental issue of reproductive aging in women: age-related decline in egg quality. More importantly, ARTs are not, and will never be, the main solution for the general population. Here, I attempt to review the scientific literature on age-related egg quality decline, based mostly on studies in mice and in humans. Emphasis is given to the brief period of time called oocyte maturation, which occurs just prior to ovulation. The rationale for this emphasis is that oocyte maturation represents a critical window where unfavorable ovarian conditions in older females contribute significantly to the decline of egg quality, and that science-based intervention during oocyte maturation represents the best chance of improving egg quality in older women. Finally, I summarize our own work in recent years on peri-ovulatory putrescine supplementation as a possible remedy for reproductive aging.

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Peri-ovulatory putrescine supplementation reduces embryo resorption in older mice

Abstract: This study was supported by the NSERC, the March of Dimes Foundation, and the National Natural Science Foundation of China. The authors declare no competing interest.

Cited by 19 publications

References 37 publications

The Majority of Resorptions in Old Mice Are Euploid

The Majority of Resorptions in Old Mice Are Euploid

Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

Targeting oocyte maturation to improve fertility in older women

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