Intrinsic fertility of human oocytes

Silber, Sherman J.; Kato, Keiichi; Aoyama, Naoki; Yabuuchi, Akiko; Skaletsky, Helen; Fan, Yuting; Shinohara, Kazunori; Yatabe, Noriyuki; Kobayashi, Tamotsu

doi:10.1016/j.fertnstert.2017.03.014

Cited by 58 publications

(41 citation statements)

References 28 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Percentages of blastocysts and hatched blastocysts were significantly improved when mice were supplemented with both sources of Se (see Table 1). Indeed, the loss of oocyte quality and its subsequent developmental potential has a correlative link to the overall female fertility, as it was shown previously that the rate of live birth per oocyte was significantly reduced (1% vs. 26%) in aging women (aged ≥ 42 years) compared to their younger counterparts [78]. It is generally well-established that Se deficiency impacts the level of selenoprotein synthesis [79].…”

Section: Se Effect On In Vitro Embryo Developmental Potentialmentioning

confidence: 92%

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

et al. 2019

View full text Add to dashboard Cite

Female reproductive (ovarian) aging is distinctively characterized by a markedly reduced reproductive function due to a remarkable decline in quality and quantity of follicles and oocytes. Selenium (Se) has been implicated in playing many important biological roles in male fertility and reproduction; however, its potential roles in female reproduction, particularly in aging subjects, remain poorly elucidated. Therefore, in the current study we used a murine model of female reproductive aging and elucidated how different Se-levels might affect the reproductive efficiency in aging females. Our results showed that at the end of an 8-week dietary trial, whole-blood Se concentration and blood total antioxidant capacity (TAOC) were significantly reduced in Se-deficient (0.08 mg Se/kg; Se-D) mice, whereas both of these biomarkers were significantly higher in inorganic (0.33 mg/kg; ISe-S) and organic (0.33 mg/kg; OSe-S) Se-supplemented groups. Similarly, compared to the Se-D group, Se supplementation significantly ameliorated the maintenance of follicles and reduced the rate of apoptosis in ovaries. Meanwhile, the rate of in vitro-produced embryos resulting from germinal vesicle (GV) oocytes was also significantly improved in Se-supplemented (ISe-S and OSe-S) groups compared to the Se-D mice, in which none of the embryos developed to the hatched blastocyst stage. RT-qPCR results revealed that mRNA expression of Gpx1, Gpx3, Gpx4, Selenof, p21, and Bcl-2 genes in ovaries of aging mice was differentially modulated by dietary Se levels. A considerably higher mRNA expression of Gpx1, Gpx3, Gpx4, and Selenof was observed in Se-supplemented groups compared to the Se-D group. Similarly, mRNA expression of Bcl-2 and p21 was significantly lower in Se-supplemented groups. Immunohistochemical assay also revealed a significantly higher expression of GPX4 in Se-supplemented mice. Our results reasonably indicate that Se deficiency (or marginal levels) can negatively impact the fertility and reproduction in females, particularly those of an advancing age, and that the Se supplementation (inorganic and organic) can substantiate ovarian function and overall reproductive efficiency in aging females.

show abstract

Section: Se Effect On In Vitro Embryo Developmental Potentialmentioning

confidence: 92%

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It is therefore concerning that maternal aging is associated with a precipitous decline in oocyte quality such that as many as 35% of the oocyte reserve in women aged 40 are the subject of aneuploidy, compared with only 2% for that of a woman in her 20s (3,4). This loss of oocyte quality is associated with a reduction in female fertility, with the live birthrate per oocyte declining from 26% in younger women (Ͻ35 years of age) to just 1% for women at 42 years of age (5). Notwithstanding the undoubtedly complex mechanistic basis behind this age-associated phenomenon, several studies have converged on the notion that the accumulation of oxidative damage throughout the oocyte's extended life is a major contributing factor (6 -9).…”

mentioning

confidence: 99%

Oxidative damage in naturally aged mouse oocytes is exacerbated by dysregulation of proteasomal activity

Mihalas

Bromfield

Sutherland

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

An increase in oxidative protein damage is a leading contributor to the age-associated decline in oocyte quality. By removing such damaged proteins, the proteasome plays an essential role in maintaining the fidelity of oocyte meiosis. In this study, we established that decreased proteasome activity in naturally aged, germinal vesicle (GV) mouse oocytes positively correlates with increased protein modification by the lipid aldehyde 4-hydroxynonenal (4-HNE). Furthermore, attenuation of proteasome activity in GV oocytes of young animals was accompanied by an increase in 4-HNE-modified proteins, including ␣-tubulin, thereby contributing to a reduction in tubulin polymerization, microtubule stability, and integrity of oocyte meiosis. A decrease in proteasome activity was also recapitulated in the GV oocytes of young animals following exposure to oxidative insults in the form of either hydrogen peroxide (H 2 O 2 ) or 4-HNE. We also observed that upon oxidative insult, 4-HNE exhibits elevated adduction to multiple proteasomal subunits. Notably, the inclusion of the antioxidant penicillamine, to limit propagation of oxidative stress cascades, led to a complete recovery of proteasome activity and enhanced clearance of 4-HNE-adducted ␣-tubulin during a 6-h post-treatment recovery period. This strategy also proved effective in reducing the incidence of oxidative stress-induced aneuploidy following in vitro oocyte maturation, but was ineffective for naturally aged oocytes. Taken together, our results implicate proteasome dysfunction as an important factor in the accumulation of oxidatively induced protein damage in the female germline. This discovery holds promise for the design of therapeutic interventions to address the age-dependent decline in oocyte quality.

show abstract

“…In addition, clinical studies have reported that the live birthrate per oocyte in natural cycles of IVF was higher than that in a controlled ovarian stimulation cycle, suggesting that aggressive ovarian stimulation is likely to yield a high number of oocytes that will not result in a live birth. 21,22 have reported that CC could adversely affect uterine receptivity and pregnancy outcomes during fresh embryo transfer cycles. 10,23 Furthermore, gonadotropin administration for ovarian stimulation impacts uterine receptivity.…”

Section: Pregnancy Outcomesmentioning

confidence: 99%

Effects of gonadotropin administration on clinical outcomes in clomiphene citrate‐based minimal stimulation cycle IVF

Karakida¹,

Ezoe²,

Fukuda³

et al. 2019

Reprod Medicine & Biology

Self Cite

View full text Add to dashboard Cite

Purpose Exogenous gonadotropins (EGn) have been used occasionally in clomiphene citrate (CC)‐based minimal stimulation cycles to compensate insufficient secretion of endogenous gonadotropin; however, the effectiveness of EGn supplementation remains unknown. In the present study, we assessed whether EGn improved pregnancy outcomes in CC‐based minimal stimulation cycles. Methods A total of 223 patients treated with CC and EGn (CC‐EGn group) were matched one to one to patients treated with CC only (CC group) by propensity score matching. Embryonic and pregnancy outcomes were retrospectively compared between the groups. Results The numbers of retrieved oocytes, fertilized oocytes, cleaved embryos, and cryopreserved blastocysts were increased in the CC‐EGn group compared with the CC group. However, the cumulative live birthrate was comparable between the two groups. Although the increased number of retrieved oocytes was correlated significantly with improvement of the cumulative live birthrate in both groups, the correlation tended to be lower in the CC‐EGn group than in the CC group (odds ratio, 1.193 vs 1.553). Conclusions In CC‐based minimal stimulation cycles, the stimulation should be started with CC only, and EGn administration should be scheduled only if insufficient secretion of endogenous gonadotropin is observed in the late follicular phase.

show abstract

Intrinsic fertility of human oocytes

Abstract: The intrinsic fertility per oocyte in natural cycle is far greater than reported in hyperstimulated cycles, varying robustly from 26% to 4% with age from <35 to 42 years. The curve is relatively flat until age 34, and then declines rapidly 10% per year thereafter.

Cited by 58 publications

References 28 publications

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice

Oxidative damage in naturally aged mouse oocytes is exacerbated by dysregulation of proteasomal activity

Effects of gonadotropin administration on clinical outcomes in clomiphene citrate‐based minimal stimulation cycle IVF

Contact Info

Product

Resources

About