Mechanisms of reproductive aging: conserved mechanisms and environmental factors

Abstract

The interplay of neuroendocrine processes and gonadal function is exquisitely expressed during aging. In females, loss of ovarian function results in decreased circulating estradiol. As a result, estrogen-dependent endocrine and behavioral responses decline, including impaired cognitive function reflecting the impact of declining estrogen on the hippocampus circuits, and decreased metabolic endocrine function. Concurrently, age-related changes in neuroendocrine response also contribute to the declining reproductive function. Our session considered key mechanisms in reproductive aging including the roles of ovarian function (Finch and Holmes) and the hypothalamic median eminence (Yin and Gore) with an associated age-related cognitive decline that accompanies estrogen loss (Morrison and colleagues). Effects of smoking, obesity, and insulin resistance (Sowers and colleagues) impact the timing of the perimenopause transition in women. Animal models provide excellent insights into conserved mechanisms and key overarching events that bring about endocrine and behavioral aging. Environmental factors are key triggers in timing endocrine aging with implications for eventual disease. Session presentations will be considered in the context of the broader topic of indices and predictors of aging-related change.

Figure 1

The menstrual cycle in the rhesus macaque female (data from dissertation research by Julie Wu, Ph.D.). Figures 1a, b, and c show the progression of hormone cycles over the reproductive lifespan of the female with a transition from (a) regular cycles to (b) irregular and anovulatory cycles and (c) collapse of ovarian function in the post menopausal female (from reference 3).

Figure 2

In vitro release of gonadotropin releasing hormone-I (GnRH-I) from parasaggital slices of hypothalamus. Slices were taken from young reproductive and old senescent males and females. An age-related diminution in pulse height occurred in response to norepinephrine (NE) stimulation, which was administered as a single injection made at 3–4 time points (denoted by bars) in both females (A) and males (B). Both baseline and NE induced GnRH-I differed with aging in males and females as shown in the bar graph (based on references and 20).

Figure 2

In vitro release of gonadotropin releasing hormone-I (GnRH-I) from parasaggital slices of hypothalamus. Slices were taken from young reproductive and old senescent males and females. An age-related diminution in pulse height occurred in response to norepinephrine (NE) stimulation, which was administered as a single injection made at 3–4 time points (denoted by bars) in both females (A) and males (B). Both baseline and NE induced GnRH-I differed with aging in males and females as shown in the bar graph (based on references and 20).

Figure 2

In vitro release of gonadotropin releasing hormone-I (GnRH-I) from parasaggital slices of hypothalamus. Slices were taken from young reproductive and old senescent males and females. An age-related diminution in pulse height occurred in response to norepinephrine (NE) stimulation, which was administered as a single injection made at 3–4 time points (denoted by bars) in both females (A) and males (B). Both baseline and NE induced GnRH-I differed with aging in males and females as shown in the bar graph (based on references and 20).

Figure 3

Schematic diagram showing the potential effects of exposure to EDCs over the lifespan of short lived (SL) or over part of the lifespan for long lived (LL) birds. The schematic is hypothetical and is based on information about longevity data from birds and the impact of EDCs on birds, both in field observations and from laboratory studies. In birds, reproduction peaks quickly in short lived birds and declines quickly with the short lifespan. In these species, intermittent exposure to EDCs would be predicted to impair reproduction, which may impact short lived species more drastically than long lived birds depending on the timing of exposure during the life cycle. High exposure would be deleterious for both short and long lived birds resulting in reduced fitness and possibly shortened reproductive lifespan (based on references and 21).