Understanding the Role of Telomere Dynamics in Normal and Dysfunctional Human Reproduction

Abstract

In modern society, fertility problems and demand of treatment seem to be on the rise, which led to an increased interest in research regarding human reproduction. Among these efforts, the study of the molecular senescence process has gain notorious popularity as aging is one of the most important variables involved in reproductive capacity and since the comprehension of telomere dynamics has become an important and influential theme. This new knowledge regarding the reproductive aging process is expected to offer new tools to understand the acquisition, maintenance, and loss of fertility potential. Therefore, this review seeks to clarify the relevance of molecular aging (evaluated by telomere shortening) in human reproduction, showing that it is a dynamic and variable process modulated according to the specific tissue and stage of development. As well, it is discussed how telomere status influence the development and progression of some fertility pathologies, the outcome of assisted reproductive treatments, and programming of aging in the offspring.

Telomere-Related Disorders in Fetal Membranes Associated With Birth and Adverse Pregnancy Outcomes

“…Cell aging is a physiological process, as telomeres undergo steady attrition during the proliferation of normal cells; this can be either beneficial or detrimental to the organism. On one hand, it contributes to tumor suppression, limiting tissue damage, and possibly embryonic development, while on the other, it may be associated with aging-related diseases, impaired tissue regeneration, and cellular dysfunction, as well as pregnancy complications ( Howcroft et al, 2013 ; Burton and Krizhanovsky, 2014 ; Menon et al, 2016 ; Arias-Sosa, 2018 ).…”

“…The concept of placental cell aging in term delivery was first proposed in the 1970s ( Rosso, 1976 ); however, until recently few studies had reported on cellular senescence related to oxidative stress and its consequent morphological changes ( Menon et al, 2012 ; Polettini et al, 2015b ). This process is believed to be physiological since the placenta and fetal membranes constitute temporary tissues in the maternal body, and therefore, would be “aged” and ready to be eliminated after the birth of the neonate ( Behnia et al, 2015 ; Menon, 2016 ; Cox and Redman, 2017 ; Arias-Sosa, 2018 ).…”

“…Recent investigations have revealed that term pregnancies are characterized by increased OS that induces DNA damage ( Menon, 2016 ; Cox and Redman, 2017 ; Arias-Sosa, 2018 ); therefore, TL is affected. Gestational tissues show evidence of senescence, given that the telomere attrition rate is negatively correlated with gestational age, thus the closer to term, the shorter the telomeres in fetal and placental cells ( Gielen et al, 2014 ; Casavant et al, 2019 ).…”

“…Placenta and fetal membranes constitute temporary tissues in the maternal body, and therefore, are “aged” and ready to be eliminated by the time of the term neonate is born. Thus, cellular senescence may be related to gestational complications if the process is activated prematurely ( Behnia et al, 2015 ; Menon, 2016 ; Cox and Redman, 2017 ; Arias-Sosa, 2018 ). One of the main characteristics of senescent cells is the production of inflammatory cytokines, which indicates a possible role of cellular senescence as an effector pathway that converges to trigger parturition.…”

Telomere length in granulosa cells and leukocytes: a potential marker of female fertility? A systematic review of the literature

“…Leukocyte telomere length (LTL), the most studied telomere length in clinical and epidemiological studies due to the easy accessibility of leukocytes, decreases with age [24]. The LTL attrition rate is higher in utero and during the first years of life and then it decreases during adulthood [25][26][27]. In adults, LTL attrition rates are estimated at 25 to 35 bp/year [28].…”