TY - JOUR
T1 - Ovulation and ovarian wound healing are impaired with advanced reproductive age
AU - Mara, Jamie N.
AU - Zhou, Luhan T.
AU - Larmore, Megan
AU - Johnson, Brian
AU - Ayiku, Rebecca
AU - Amargant, Farners
AU - Pritchard, Michele T.
AU - Duncan, Francesca E.
N1 - Funding Information:
This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD093726 to F.E. D and M.T. P), the Master of Science in Reproductive Science and Medicine program, and faculty startup funds from the Department of Obstetrics and Gynecology (F.E. D). R. A was supported by the Marcia L. Storch Scholarship for Undergraduate Women and a 2019 Northwestern Undergraduate Research Award. The Histology Core at KUMC is supported by the NICHD P30 HD002528 (Kansas IDDRC). The University of Virginia Center for Research and Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver NICHD/NIH (NCTRI) Grant P50 HD28934.
Publisher Copyright:
© 2020, Mara et al.
PY - 2020/5/31
Y1 - 2020/5/31
N2 - Aging is associated with reduced tissue remodeling efficiency and increased fibrosis, characterized by excess collagen accumulation and altered matrix degradation. Ovulation, the process by which an egg is released from the ovary, is one of the most dynamic cycles of tissue wounding and repair. Because the ovary is one of the first organs to age, ovulation and ovarian wound healing is impaired with advanced reproductive age. To test this hypothesis, we induced superovulation in reproductively young and old mice and determined the numbers of eggs ovulated and corpora lutea (CLs), the progesterone producing glands formed post-ovulation. Reproductively old mice ovulated fewer eggs and had fewer CLs relative to young controls. Moreover, reproductively old mice exhibited a greater number of oocytes trapped within CLs and expanded cumulus oocyte complexes within unruptured antral follicles, indicative of failed ovulation. In addition, post-ovulatory tissue remodeling was compromised with age as evidenced by reduced CL vasculature, increased collagen, decreased hyaluronan, decreased cell proliferation and apoptosis, impaired wound healing capacity, and aberrant morphology of the ovarian surface epithelium (OSE). These findings demonstrate that ovulatory dysfunction is an additional mechanism underlying the age-related loss of fertility beyond the reduction of egg quantity and quality.
AB - Aging is associated with reduced tissue remodeling efficiency and increased fibrosis, characterized by excess collagen accumulation and altered matrix degradation. Ovulation, the process by which an egg is released from the ovary, is one of the most dynamic cycles of tissue wounding and repair. Because the ovary is one of the first organs to age, ovulation and ovarian wound healing is impaired with advanced reproductive age. To test this hypothesis, we induced superovulation in reproductively young and old mice and determined the numbers of eggs ovulated and corpora lutea (CLs), the progesterone producing glands formed post-ovulation. Reproductively old mice ovulated fewer eggs and had fewer CLs relative to young controls. Moreover, reproductively old mice exhibited a greater number of oocytes trapped within CLs and expanded cumulus oocyte complexes within unruptured antral follicles, indicative of failed ovulation. In addition, post-ovulatory tissue remodeling was compromised with age as evidenced by reduced CL vasculature, increased collagen, decreased hyaluronan, decreased cell proliferation and apoptosis, impaired wound healing capacity, and aberrant morphology of the ovarian surface epithelium (OSE). These findings demonstrate that ovulatory dysfunction is an additional mechanism underlying the age-related loss of fertility beyond the reduction of egg quantity and quality.
KW - Fibrosis
KW - Ovary
KW - Ovulation
KW - Reproductive aging
KW - Wound healing
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U2 - 10.18632/aging.103237
DO - 10.18632/aging.103237
M3 - Article
C2 - 32407290
AN - SCOPUS:85086051140
SN - 1945-4589
VL - 12
SP - 9686
EP - 9713
JO - Aging
JF - Aging
IS - 10
ER -