Prolonging Reproductive Life after Cancer: The Need for Fertoprotective Therapies

Woodard, Terri L.; Bolcun-Filas, Ewelina

doi:10.1016/j.trecan.2016.03.006

Cited by 20 publications

(14 citation statements)

References 93 publications

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“… 31 High oestrogen levels cause release of the luteinising hormones which triggers ovulation, which might imply more cycles and rapid depletion of oocytes, consequently leading to an earlier menopause. 32 This can be supported by a recent review study which reported that women with type II diabetes mellitus tend to have an earlier menopause although additional evidence is required to clarify this association. 33 …”

Section: Discussionmentioning

confidence: 86%

Dietary intake and age at natural menopause: results from the UK Women’s Cohort Study

Dunneram

Greenwood

Burley

et al. 2018

J Epidemiol Community Health

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BackgroundAge at natural menopause is a matter of concern for women of reproductive age as both an early or late menopause may have implications for health outcomes.MethodsStudy participants were women aged 40–65 years who had experienced a natural menopause from the UK Women’s Cohort Study between baseline and first follow-up. Natural menopause was defined as the permanent cessation of menstrual periods for at least 12 consecutive months. A food frequency questionnaire was used to estimate diet at baseline. Reproductive history of participants was also recorded. Regression modelling, adjusting for confounders, was used to assess associations between diet and age at natural menopause.ResultsDuring the 4-year follow-up period, 914 women experienced a natural menopause. A high intake of oily fish and fresh legumes were associated with delayed onset of natural menopause by 3.3 years per portion/day (99% CI 0.8 to 5.8) and 0.9 years per portion/day (99% CI 0.0 to 1.8), respectively. Refined pasta and rice was associated with earlier menopause (per portion/day: −1.5 years, 99% CI −2.8 to −0.2). A higher intake of vitamin B6 (per mg/day: 0.6 years, 99% CI 0.1 to 1.2) and zinc (per mg/day: 0.3 years, 99% CI −0.0 to 0.6) was also associated with later age at menopause. Stratification by age at baseline led to attenuated results.ConclusionOur results suggest that some food groups (oily fish, fresh legumes, refined pasta and rice) and specific nutrients are individually predictive of age at natural menopause.

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Section: Discussionmentioning

confidence: 86%

Dietary intake and age at natural menopause: results from the UK Women’s Cohort Study

Dunneram

Greenwood

Burley

et al. 2018

J Epidemiol Community Health

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“…The fact that mammalian females are born with the pool of oocytes they will use in their lifetime, represents a challenge since these cells are exposed to several environmental aggressions during the life of the individual that may ultimately harm them. Among others, most cancer therapy treatments are known to produce infertility as a side-effect due to the cessation of follicle pool (Woodard and Bolcun-Filas, 2016). Thus, many efforts are being invested in finding ways to preserve fertility for cancer patients (Woodard and Bolcun-Filas, 2016).…”

Section: Introductionmentioning

confidence: 99%

ATR function is indispensable to allow proper mammalian follicle development

et al. 2019

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Mammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.

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“…4,5 ). The loss of the PF reserve causes infertility and breakdown of the endocrine function of the ovary, resulting in health impairments such as osteoporosis 6 . In contrast to the PFs, growing follicles are unaffected by a low dosage of irradiation.…”

mentioning

confidence: 99%

p63 uses a switch-like mechanism to set the threshold for induction of apoptosis

et al. 2020

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The p53 homolog TAp63α is the transcriptional key regulator of genome integrity in oocytes. After DNA damage, TAp63α is activated by multistep phosphorylation involving multiple phosphorylation events by the kinase CK1, which triggers the transition from a dimeric and inactive conformation to an open and active tetramer that initiates apoptosis. By measuring activation kinetics in ovaries and single-site phosphorylation kinetics in vitro with peptides and full-length protein, we show that TAp63α phosphorylation follows a biphasic behavior. Although the first two CK1 phosphorylation events are fast, the third one, which constitutes the decisive step to form the active conformation, is slow. Structure determination of CK1 in complex with differently phosphorylated peptides reveals the structural mechanism for the difference in the kinetic behavior based on an unusual CK1/TAp63α substrate interaction in which the product of one phosphorylation step acts as an inhibitor for the following one.

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Prolonging Reproductive Life after Cancer: The Need for Fertoprotective Therapies

Cited by 20 publications

References 93 publications

Dietary intake and age at natural menopause: results from the UK Women’s Cohort Study

Dietary intake and age at natural menopause: results from the UK Women’s Cohort Study

ATR function is indispensable to allow proper mammalian follicle development

p63 uses a switch-like mechanism to set the threshold for induction of apoptosis

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