TY - JOUR
T1 - Immature Follicular Origins and Disrupted Oocyte Growth Pathways Contribute to Decreased Gamete Quality During Reproductive Juvenescence in Mice
AU - Kusuhara, Atsuko
AU - Babayev, Elnur
AU - Zhou, Luhan T.
AU - Singh, Vijay P.
AU - Gerton, Jennifer L.
AU - Duncan, Francesca E.
N1 - Funding Information:
This work was supported by the MS-RSM Program and the Center for Reproductive Health After Disease (P50 HD076188) from the National Centers for Translational Research in Reproduction and Infertility (NCTRI) and the Stowers Institute for Medical Research.
Publisher Copyright:
© Copyright © 2021 Kusuhara, Babayev, Zhou, Singh, Gerton and Duncan.
PY - 2021/6/16
Y1 - 2021/6/16
N2 - Egg quality dictates fertility outcomes, and although there is a well-documented decline with advanced reproductive age, how it changes during puberty is less understood. Such knowledge is critical, since advances in Assisted Reproductive Technologies are enabling pre- and peri-pubertal patients to preserve fertility in the medical setting. Therefore, we investigated egg quality parameters in a mouse model of the pubertal transition or juvenescence (postnatal day; PND 11–40). Animal weight, vaginal opening, serum inhibin B levels, oocyte yield, oocyte diameter, and zona pellucida thickness increased with age. After PND 15, there was an age-associated ability of oocytes to resume meiosis and reach metaphase of meiosis II (MII) following in vitro maturation (IVM). However, eggs from the younger cohort (PND 16–20) had significantly more chromosome configuration abnormalities relative to the older cohorts and many were at telophase I instead of MII, indicative of a cell cycle delay. Oocytes from the youngest mouse cohorts originated from the smallest antral follicles with the fewest cumulus layers per oocyte, suggesting a more developmentally immature state. RNA Seq analysis of oocytes from mice at distinct ages revealed that the genes involved in cellular growth signaling pathways (PI3K, mTOR, and Hippo) were consistently repressed with meiotic competence, whereas genes involved in cellular communication were upregulated in oocytes with age. Taken together, these data demonstrate that gametes harvested during the pubertal transition have low meiotic maturation potential and derive from immature follicular origins.
AB - Egg quality dictates fertility outcomes, and although there is a well-documented decline with advanced reproductive age, how it changes during puberty is less understood. Such knowledge is critical, since advances in Assisted Reproductive Technologies are enabling pre- and peri-pubertal patients to preserve fertility in the medical setting. Therefore, we investigated egg quality parameters in a mouse model of the pubertal transition or juvenescence (postnatal day; PND 11–40). Animal weight, vaginal opening, serum inhibin B levels, oocyte yield, oocyte diameter, and zona pellucida thickness increased with age. After PND 15, there was an age-associated ability of oocytes to resume meiosis and reach metaphase of meiosis II (MII) following in vitro maturation (IVM). However, eggs from the younger cohort (PND 16–20) had significantly more chromosome configuration abnormalities relative to the older cohorts and many were at telophase I instead of MII, indicative of a cell cycle delay. Oocytes from the youngest mouse cohorts originated from the smallest antral follicles with the fewest cumulus layers per oocyte, suggesting a more developmentally immature state. RNA Seq analysis of oocytes from mice at distinct ages revealed that the genes involved in cellular growth signaling pathways (PI3K, mTOR, and Hippo) were consistently repressed with meiotic competence, whereas genes involved in cellular communication were upregulated in oocytes with age. Taken together, these data demonstrate that gametes harvested during the pubertal transition have low meiotic maturation potential and derive from immature follicular origins.
KW - aging
KW - cumulus cells
KW - follicle
KW - meiosis
KW - oocyte
KW - puberty
KW - spindle
KW - zona pellucida
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U2 - 10.3389/fcell.2021.693742
DO - 10.3389/fcell.2021.693742
M3 - Article
C2 - 34222262
AN - SCOPUS:85115446986
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 693742
ER -