Four recommendations to tackle the complex reality of transdisciplinary, natural experiment research.

Natural experiments are often used to study interventions in which randomization to control versus intervention conditions are impossible. Nature-based interventions (i.e., programs designed to increase human interaction with nature and improve human health) are commonly studied as natural experiments. We used a natural experiment design to explore the benefits of ecological rehabilitation of parks on biodiversity and resident health in low-income, minoritized neighborhoods in Detroit, MI. Given the complexities and interconnectedness of lived experiences, community needs, and ecological health, this research design has presented challenges. Based on our experiences, we pose four key recommendations for researchers and practitioners conducting natural experiments, nature-based interventions, and those working in low-income, minoritized neighborhoods. We use the explicit examples of challenges faced as rationale for these recommendations. The key recommendations are (1) Engage with community leaders; (2) Build a transdisciplinary team and work closely; (3) Examine privilege; and (4) Create a unified vision.

The effects of contemporary redlining on the mental health of Black residents.

Understanding how structural racism, including institutionalized practices such as redlining, influence persistent inequities in health and neighborhood conditions is still emerging in urban health research. Such research often focuses on historical practices, giving the impression that such practices are a thing of the past. However, mortgage lending bias can be readily detected in contemporary datasets and is an active form of structural racism with implications for health and wellbeing. The objective of the current study was to test for associations among multiple measures of mental health and a measure of contemporary redlining. We linked a redlining index constructed using Home Mortgage Disclosure Act data (2007-2013) to 2021 health data for Black/African American participants in the Study of Active Neighborhoods in Detroit (n = 220 with address data). We used multilevel regression models to examine the relationship between redlining and a suite of mental health outcomes (perceived stress, anxiety, depressive symptoms, and satisfaction with life), accounting for covariates including racial composition of the neighborhood. We considered three mediating factors: perceived neighborhood cohesion, aesthetics, and discrimination. Although all participants lived in redlined neighborhoods compared to the complete Detroit Metropolitan area, participants with very low income, low levels of experienced discrimination, and lower perceptions of neighborhood aesthetics resided in highly redlined neighborhoods (score ≥5). We observed that higher resident-reported neighborhood aesthetics were found in neighborhoods with lower redlining scores and were associated with higher levels of satisfaction with life. We found that lower levels of redlining were significantly associated with higher levels of perceived discrimination, which was significantly, positively associated with anxiety, depressive symptoms, and perceived stress scores. Our findings highlight that contemporary redlining practices may influence the aesthetics of the built environment because these neighborhoods experience less investment, with implications for residents' satisfaction with life. However, areas with lower redlining may be areas where Black/African American people experience increased perceived discrimination.

C-reactive protein and telomerase reverse transcriptase (TERT) associate with chronic disease markers in a sample from low-income neighborhoods in Detroit, Michigan.

Racial and ethnic minorities in economically deprived inner cities experience high rates of chronic diseases compared to neighborhoods with higher socioeconomic status (SES). However, these economically deprived populations are understudied in terms of biomarkers associated with chronic disease risk which include C-reactive protein (CRP), telomerase reverse transcriptase (TERT), and glycosylated hemoglobin (A1C). We examined relationships between CRP and TERT and chronic disease indicators (body mass index [BMI] and A1C) in two low-income, predominantly African American (AA) neighborhoods in Detroit, Michigan. Sixty-nine adults (43 females, 26 males, mean age 46 years [y], standard deviation [SD] â€‹= â€‹15.9) completed a health survey, anthropometry, and finger stick blood tests. A1C was measured using A1CNow test strips, and CRP and TERT levels were measured using enzyme-linked immunosorbent assay (ELISA) with samples extracted from dried blood spots. We examined CRP (mean â€‹= â€‹4.9, SD â€‹= â€‹3.1), TERT (mean â€‹= â€‹32.5, SD â€‹= â€‹15.1), and A1C (mean â€‹= â€‹5.4, SD â€‹= â€‹1.0) by BMI category. We fitted restricted maximum likelihood regression models to evaluate associations between CRP, TERT, BMI, and A1C, after adjustment for demographics and inclusion of a random effect for the neighborhood. In this predominantly AA sample (91%, 63/69), 68% had levels of CRP (means â€‹= â€‹4.8 â€‹mg/L, SD â€‹= â€‹3.0 for AAs; 6.4 â€‹mg/L, SD â€‹= â€‹3.9 for all others) indicative of chronic inflammation (CRP greater than 3 â€‹mg/L). BMI was significantly associated with CRP (p â€‹= â€‹0.004) and TERT (p â€‹= â€‹0.026). TERT levels indicate that being overweight is associated with markers of chromosome remodeling, suggestive of chronic disease. CRP followed a similar trend with overweight individuals having higher inflammation and risk of chronic disease. Our findings warrant further exploration of additional factors that may influence CRP and TERT. Furthermore, examining populations in a more ethnically and/or economically diverse, yet still high proportion minority, sample will fill a knowledge gap in this understudied field.

Time Spent in Nature Is Associated with Increased Pro-Environmental Attitudes and Behaviors.

Urbanization, screen dependency, and the changing nature of childhood and parenting have led to increased time indoors, creating physical and emotional distancing from nature and time spent in natural environments. Substantial evidence from observational and intervention studies indicates that overall time spent in nature leads to increased perceived value for connectedness to nature and, subsequently, greater pro-environmental attitudes and behaviors (PEAB). This narrative review of the recent literature evaluates associations between time spent in nature with values ascribed to nature and nature connectedness, as well as PEAB. We discuss the influence of nature exposure and education in childhood on subsequent development of PEAB in adulthood. We analyze theoretical frameworks applied to this research as well as metrics employed, populations studied, and individual and societal values before presenting limitations of this research. We conclude with suggestions for future research directions based on current knowledge, underscoring the importance of promoting time spent in nature and PEAB in the face of growing challenges to planetary health. Research indicates that overall time spent in nature, regardless of the quality of environmental conditions, leads to increased perceived values ascribed to nature, which is associated with PEAB; however, this literature is predominantly cross-sectional. Furthermore, personal and social factors may influence PEAB. Thus, more longitudinal studies that consider these factors are needed to assess the duration and frequency of time spent in nature in childhood and its impact on PEAB throughout the life course. Identifying contexts which cultivate PEAB and reverse alienation from nature beginning in childhood may better sensitize adults to the urgency of environmental issues such as climate change, which adversely impact individual and environmental health.

Feelings of safety during daytime walking: associations with mental health, physical activity and cardiometabolic health in high vacancy, low-income neighborhoods in Detroit, Michigan.

INTRODUCTION: Individuals living in low-income neighborhoods have disproportionately high rates of obesity, Type-2 diabetes, and cardiometabolic conditions. Perceived safety in one's neighborhood may influence stress and physical activity, with cascading effects on cardiometabolic health. METHODS: In this study, we examined relationships among feelings of safety while walking during the day and mental health [perceived stress (PSS), depression score], moderate-to-vigorous physical activity (PA), Body Mass Index (BMI), and hemoglobin A1C (A1C) in low-income, high-vacancy neighborhoods in Detroit, Michigan. We recruited 69 adults who wore accelerometers for one week and completed a survey on demographics, mental health, and neighborhood perceptions. Anthropometrics were collected and A1C was measured using A1CNow test strips. We compiled spatial data on vacant buildings and lots across the city. We fitted conventional and multilevel regression models to predict each outcome, using perceived safety during daytime walking as the independent variable of interest and individual or both individual and neighborhood-level covariates (e.g., number of vacant lots). Last, we examined trends in neighborhood features according to perceived safety. RESULTS: In this predominantly African American sample (91%), 47% felt unsafe during daytime walking. Feelings of perceived safety significantly predicted PSS (ß = - 2.34, p = 0.017), depression scores (ß = - 4.22, p = 0.006), and BMI (ß = - 2.87, p = 0.01), after full adjustment. For PA, we detected a significant association for sex only. For A1C we detected significant associations with blighted lots near the home. Those feeling unsafe lived in neighborhoods with higher park area and number of blighted lots. CONCLUSION: Future research is needed to assess a critical pathway through which neighborhood features, including vacant or poor-quality green spaces, may affect obesity-via stress reduction and concomitant effects on cardiometabolic health.

A Scoping Review of the Health Benefits of Nature-Based Physical Activity.

The health benefits of physical activity and spending time in nature are well established. However, youths and adults in the United States are not participating in sufficient levels of physical activity and are not spending much time outdoors. Recently, the need for equitable access to nature for all populations has been receiving more public health attention, though a specific focus on nature-based physical activity has been limited. The purpose of this scoping review is to operationalize the health benefits of nature-based physical activity in order to provide guidance for collaborations to program administrators, advocates, and researchers. Peer-reviewed literature is found in PubMed, Medline, Web of Science, and Google Scholar as well as in published reviews of the literature. The literature is divided into three categories of: 1) amount and location of nature-based components and physical activity; 2) added health benefits of exposure to nature-based components and physical activity; and 3) nature-based components and physical activity effect on non-white, marginalized, and vulnerable populations. This review supports and encourages multiple strategies to increase nature-based physical activity as this provides even greater benefit to health and wellness than exposure to nature or physical activity alone. Although many of the physical and mental health benefits of nature and physical activity are well established, additional research is needed to better understand the relationship between exposure to nature and nature-based physical activity, which will require greater investment and support from funding agencies.

The effect of green walking on heart rate variability: A pilot crossover study.

We investigated the effects of regular walking in green and suburban environments on heart rate variability (HRV) and blood pressure (BP) in middle-aged adults. Twenty-three adults participated in a non-randomized crossover experiment comprised of once-weekly 50-min moderate-intensity walking sessions. Separated by a two-week washout period, participants walked for three weeks in each of two treatment conditions (green and suburban) in a local arboretum and suburban sidewalks of Chaska, MN. Eleven participants completed green walking first and 12 suburban walking first. Walks were split into 15-min intra-walk phases, with phases representing each walk's beginning, middle, and final 15-min. Repeated measures linear mixed models evaluated (1) HRV phase differences between treatments and HRV change within treatments, and (2) pre- and post-walk BP differences between treatments and pre-to post-walk BP changes. Intra-walk phase analyses revealed higher HRV during green walking vs. suburban walking during phase 2 (p < 0.0001) and phase 3 (p = 0.02). Less HRV reduction was seen between intra-walk phases 1 and 2 during green vs. suburban walking (p = 0.02). Pre-to post-walk changes revealed decreased mean systolic BP for both green (p = 0.0002) and suburban (p = 0.003) walking conditions, but not for diastolic BP. Post-walk BP results were similar after both green walking and suburban walking. In summary, walking sessions in a green environment elicited greater beneficial HRV responses compared to a suburban environment. Additionally, walking in either environment, green or suburban, promoted reductions in systolic BP.

Walking Green: Developing an Evidence Base for Nature Prescriptions.

Although the health benefits of exercise and exposure to nature are well established, most evidence of their interaction comes from acute observations of single sessions of activity. However, documenting improved health outcomes requires ongoing interventions, measurement of multiple outcomes, and longitudinal analyses. We conducted a pilot study to guide the development of a protocol for future longitudinal studies that would assess multiple physiological and psychological outcomes. Herein, we report psychological outcomes measured from thirty-eight participants before and after three conditions: a 50 min walk on a forest path, a 50 min walk along a busy road, and a period of activities of daily living. Changes in positive and negative affect, anxiety, perceived stress, and working memory are reported. We benchmark these results to existing studies that used similar protocols and also identify elements of the protocol that might impair recruitment or retention of subjects in longer-term studies. Linear mixed-models regression revealed that walking improved psychological state when compared to activities of daily living, regardless of walk environment (p < 0.05). Comparison of mean differences showed that forest walks yielded the largest and most consistent improvements in psychological state. Thus, despite a protocol that required a 3.5 h time commitment per laboratory visit, the beneficial effects of walking and exposure to a forested environment were observed.

Effects of freshwater blue spaces may be beneficial for mental health: A first, ecological study in the North American Great Lakes region.

Research linking green space and mental health abounds. It also appears that oceanic blue spaces may be salutogenic, benefitting mental health through their expansive viewscapes, and possibly auditory and olfactory stimuli. Yet, it is unknown whether the same is true for freshwater bodies. In this ecological study, we explored associations between hospitalizations for anxiety/mood disorder in Michigan (>30,000) and proximity to the North American Great Lakes. As a sensitivity analysis, we examined associations for 15 different inland lake sizes. Results showed small, protective effects for distance to Great Lake (ß = 0.06, p<0.001) and percentage of inland lakes (ß = -0.04, p = 0.004). Unexpectedly, shorter distance to nearest inland lake was associated with higher anxiety/mood disorder hospitalizations. The protective effects of percentage area covered by inland lakes was observed for all lake sizes. These initial findings provide a foundation for future individual-level research with finer measurement of health outcomes and blue space exposure.

Changes in Psychological and Cognitive Outcomes after Green versus Suburban Walking: A Pilot Crossover Study.

This study investigated the acute effects of repeated walking sessions within green and suburban environments on participants' psychological (anxiety and mood) and cognitive (directed-attention) outcomes. Twenty-three middle-aged adults (19 female) participated in a non-randomized crossover study comprised of once-weekly 50-min moderate-intensity walking sessions. Participants walked for three weeks in each of two treatment conditions: green and suburban, separated by a two-week washout period. Eleven participants completed green walking first and 12 suburban walking first. For each walk, we used validated psychological questionnaires to measure pre- and post-walk scores for: (1) mood, evaluated via the Positive and Negative Affect Schedule (PANAS); (2) anxiety, assessed by the State-Trait Anxiety Inventory (STAI-S); and (3) directed-attention, measured using the visual Backwards Digit Span test (BDS). Repeated measures linear mixed models assessed pre- to post-walk changes within-treatment conditions and post-walk contrasts between-treatment conditions. Results indicated that anxiety decreased after green walking and increased after suburban walking (-1.8 vs. +1.1 units, respectively; p = 0.001). For mood, positive affect improved after green walking and decreased after suburban walking (+2.3 vs. -0.3 units, respectively; p = 0.004), and negative affect decreased after green walking and remained similar after suburban walking (-0.5 vs. 0 units, respectively; p = 0.06). Directed-attention did not improve from pre- to post-walk for either condition. Our results suggested that green walking may be more effective at reducing state anxiety and increasing positive affect compared to suburban walking.

Accelerated Episodic Luteinizing Hormone Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca Mulatta) Exposed to Testosterone during Early-to-Mid Gestation.

BACKGROUND/AIMS: Ovarian theca cell hyperandrogenism in women with polycystic ovary syndrome (PCOS) is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic luteinizing hormone (LH) release. The resultant LH hypersecretion, likely the product of accelerated episodic release of gonadotropin-releasing hormone (GnRH) from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized (PA) female monkeys exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. METHODS: A total of 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. RESULTS: Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0-10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. CONCLUSION: Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy.

Progesterone receptor A (PRA) and PRB-independent effects of progesterone on gonadotropin-releasing hormone release.

Progesterone's (P4) negative feedback actions in the female reproductive axis are exerted in part by suppression of hypothalamic GnRH release. Here we show that P4 can inhibit GnRH release by a mechanism independent of a nuclear P4 receptor (PR(A/B)). Injections of P4, but not vehicle, allopregnanolone, or dexamethasone, acutely suppressed LH levels in both wild-type and P4 receptor knockout ovariectomized mice; pituitary responsiveness to GnRH was retained during P4 treatment, indicating a hypothalamic action. Superfusion of GnRH-producing GT1-7 cells with medium containing 10(-7) m P4 produced a rapid reduction in GnRH release. Incubation with P4 (10(-9) to 10(-7) M) inhibited forskolin-stimulated cAMP accumulation; cotreatment with pertussis toxin prevented this effect. Treatment of GT1-7 cell membranes with P4 caused activation of an inhibitory G protein (G(i)), as shown by immunoprecipitation with a G(i) antibody of most of the increase in membrane-bound [(35)S]GTPgamma-S. Saturation binding analyses demonstrated the presence of a high affinity (K(d) 5.85 nM), limited capacity (Bmax 62.2 nM) binding site for P4. RT-PCR analysis revealed the presence of mRNAs encoding both isoforms of the membrane P4 receptors, mPRalpha and mPRbeta. Western blotting, immunocytochemistry, and flow cytometry experiments similarly revealed expression of mPR proteins in the plasma membranes of GT1-7 cells. Treatment with mPRalpha siRNA attenuated specific P4 binding to GT1-7 cell membranes and reversed the P4 inhibition of cAMP accumulation. Taken together, our results suggest that negative feedback actions of P4 include rapid PR(A/B)-independent effects on GnRH release that may in part be mediated by mPRs.

Effects of progesterone on male-mediated infant-directed aggression.

Many species that engage in parental behavior exhibit infanticide under certain circumstances. The neural signals regulating the transition from infant care giver to infant killer and back remain unclear. Previously we demonstrated that progesterone (P) and its receptor (PR) have inhibitory effects on parental behavior and increase infant-directed aggression in male mice. In the present studies we sought to elucidate the mechanisms by which the effects of P are manifested. Because the onset of parental behavior in females is associated with the withdrawal of P at the end of pregnancy we tested the hypothesis that withdrawal of P would similarly enhance parental behavior in males. Virgin male mice were implanted with P or vehicle for 21 days, replicating the duration of pregnancy in females. Tests were run for parental and infanticidal behavior 5 days after removal of the capsules. P increased the proportion of nonparental males that attacked pups. However, neither the number of males exhibiting parental care nor the quality of care was affected by P treatment. Serum P and testosterone (T) levels were not different from controls at the time of behavioral testing indicating continued elevations in peripheral hormones are not required for the expression of infanticide. In conclusion, withdrawal of P does not trigger the onset of parental behavior in males. Rather, prior exposure to P induces persistent infanticidal behavior in adult male mice.

Fasting-induced suppression of LH secretion does not require activation of ATP-sensitive potassium channels.

Reproductive hormone secretions are inhibited by fasting and restored by feeding. Metabolic signals mediating these effects include fluctuations in serum glucose, insulin, and leptin. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose sensing and many actions of insulin and leptin in neurons, we assessed their role in suppressing LH secretion during food restriction. Vehicle or a K(ATP) channel blocker, tolbutamide, was infused into the lateral cerebroventricle in ovariectomized mice that were either fed or fasted for 48 h. Tolbutamide infusion resulted in a twofold increase in LH concentrations in both fed and fasted mice compared with both fed and fasted vehicle-treated mice. However, tolbutamide did not reverse the suppression of LH in the majority of fasted animals. In sulfonylurea (SUR)1-null mutant (SUR1(-/-)) mice, which are deficient in K(ATP) channels, and their wild-type (WT) littermates, a 48-h fast was found to reduce serum LH concentrations in both WT and SUR(-/-) mice. The present study demonstrates that 1) blockade of K(ATP) channels elevates LH secretion regardless of energy balance and 2) acute fasting suppresses LH secretion in both SUR1(-/-) and WT mice. These findings support the hypothesis that K(ATP) channels are linked to the regulation of gonadotropin-releasing hormone (GnRH) release but are not obligatory for mediating the effects of fasting on GnRH/LH secretion. Thus it is unlikely that the modulation of K(ATP) channels either as part of the classical glucose-sensing mechanism or as a component of insulin or leptin signaling plays a major role in the suppression of GnRH and LH secretion during food restriction.

Neuroendocrine consequences of androgen excess in female rodents.

Androgens exert significant organizational and activational effects on the nervous system and behavior. Despite the fact that female mammals generally produce low levels of androgens, relative to the male of the same species, increasing evidence suggests that androgens can exert profound effects on the normal physiology and behavior of females during fetal, neonatal, and adult stages of life. This review examines the effects of exposure to androgens at three stages of development--as an adult, during early postnatal life and as a fetus, on reproductive hormone secretions in female rats. We examine the effects of androgen exposure both as a model of neuroendocrine sexual differentiation and with respect to the role androgens play in the normal female. We then discuss the hypothesis that androgens may cause epigenetic modification of estrogen target genes in the brain. Finally we consider the clinical consequences of excess androgen exposure in women.

Vasopressin regulation of the proestrous luteinizing hormone surge in wild-type and Clock mutant mice.

In the female mouse, ovulation and estrous cyclicity are under both hormonal and circadian control. We have shown that mice with a mutation in the core circadian gene Clock have abnormal estrous cycles and do not have a luteinizing hormone (LH) surge on the afternoon of proestrus due to a defect at the hypothalamic level. In the present study, we tested the hypotheses that vasopressin (AVP) can act as a circadian signal to regulate the proestrous release of LH, and that this signal is deficient in the Clock mutant. We found that Avp expression in the suprachiasmatic nucleus (SCN) and AVP 1a receptor (Avpr1a) expression in the hypothalamus is reduced in Clock mutant mice compared to wild-type mice. Intracerebroventricular (i.c.v.) injection of AVP on the afternoon of proestrus is sufficient to induce LH secretion, which reaches surge levels in 50% of Clock mutant mice. The effect of AVP on the Clock mutant LH surge is mediated by AVPR1A, as co-infusion of AVP and an AVPR1A-specific antagonist prevents AVP induction of LH release, although infusion of an AVPR1A antagonist into wild-type mice failed to prevent a proestrous LH surge. These results suggest that reduced hypothalamic AVP signaling plays a role in the absence of the proestrous LH surge in Clock mutant mice. The results also support the hypothesis that AVP produced by the SCN may be a circadian signal that regulates LH release.

Photoperiodic regulation of compensatory testicular hypertrophy in hamsters.

In mammals, removal of one testis results in compensatory testicular hypertrophy (CTH) of the remaining gonad. Although CTH is ubiquitous among juveniles of many species, laboratory rats, laboratory mice, and humans unilaterally castrated in adulthood fail to display CTH. We documented CTH in pre- and postpubertally hemi-castrated Syrian and Siberian hamsters and tested whether day length affects CTH in juvenile and adult Siberian hamsters. Robust CTH was evident in long-day hemi-castrates of both species and was preceded by increased serum FSH concentrations in juvenile Siberian hamsters. In sharp contrast, CTH was undetectable in short-day hemi-castrated Siberian hamsters for several months and only made its appearance with the development of neuroendocrine refractoriness to short day lengths; serum FSH concentrations of juveniles also did not increase above sham-castrate values until the onset of refractoriness. Long-day hemi-castrated Siberian hamsters with hypertrophied testes underwent complete gonadal regression after transfer to short days, albeit at a reduced rate for the first 3 weeks of treatment. Blood testosterone concentrations of adult hamsters did not differ between long-day hemicastrates and sham-castrates 9-12 weeks after surgery. We conclude that CTH is suppressed by short day lengths in Siberian hamsters at all ages and stages of reproductive development; in short day lengths, but not long day lengths, the remaining testis produces sufficient negative feedback inhibition to restrain FSH hypersecretion and prevent CTH.

Fetal origins of developmental plasticity: animal models of induced life history variation.

The interaction of the genetic program with the environment shapes the development of an individual. Accumulating data from animal models indicate that prenatal and early-postnatal events (collectively called "early-life events") can initiate long-term changes in the expression of the genetic program which persist, or may only become apparent, much later in the individual's life. Researchers working with humans or animal models of human diseases often view the effects of early-life events through the lens of pathology, with a focus on whether the events increase the risk for a particular disease. Alternatively, comparative biologists often view the effects of early-life events through the lens of evolution and adaptation by natural selection; they investigate the processes by which environmental conditions present early in life may prompt the adoption of different developmental pathways leading to alternative life histories. Examples of both approaches are presented in this article. This article reviews the concepts of phenotypic plasticity, natural selection, and evidence from animal models that early-life events can program the activity of the neuroendocrine system, at times altering life history patterns in an adaptive manner. Data from seasonally breeding rodents are used to illustrate the use of maternally derived information to alter the life history of young. In several species, the maternal system transfers photoperiodic information to the young in utero. This maternally derived information alters the response of young to photoperiods encountered later and life, producing seasonally distinct life histories.

Circadian clock mutation disrupts estrous cyclicity and maintenance of pregnancy.

Classic experiments have shown that ovulation and estrous cyclicity are under circadian control and that surgical ablation of the suprachiasmatic nuclei (SCN) results in estrous acyclicity in rats. Here, we characterized reproductive function in the circadian Clock mutant mouse and found that the circadian Clock mutation both disrupts estrous cyclicity and interferes with the maintenance of pregnancy. Clock mutant females have extended, irregular estrous cycles, lack a coordinated luteinizing hormone (LH) surge on the day of proestrus, exhibit increased fetal reabsorption during pregnancy, and have a high rate of full-term pregnancy failure. Clock mutants also show an unexpected decline in progesterone levels at midpregnancy and a shortened duration of pseudopregnancy, suggesting that maternal prolactin release may be abnormal. In a second set of experiments, we interrogated the function of each level of the hypothalamic-pituitary-gonadal (HPG) axis in order to determine how the Clock mutation disrupts estrous cyclicity. We report that Clock mutants fail to show an LH surge following estradiol priming in spite of the fact that hypothalamic levels of gonadotropin-releasing hormone (GnRH), pituitary release of LH, and serum levels of estradiol and progesterone are all normal in Clock/Clock females. These data suggest that Clock mutants lack an appropriate circadian daily-timing signal required to coordinate hypothalamic hormone secretion. Defining the mechanisms by which the Clock mutation disrupts reproductive function offers a model for understanding how circadian genes affect complex physiological systems.

Chemosensory stimulation of luteinizing hormone secretion in male Siberian hamsters (Phodopus sungorus).

Male Siberian hamsters (Phodopus sungorus) housed in long days (LD), but not short days (SD) release luteinizing hormone (LH) when exposed to females. This study examined whether this response is specific to a female and identifies the source of a stimulus that induces LH release. Serum concentrations of LH, testosterone (T), follicle stimulating hormone (FSH), and cortisol were examined in all experiments. T concentrations mirrored the LH response; FSH and cortisol were unchanged in response to all stimuli. Exposure to an LD female, irrespective of her reproductive status, but not an SD female, elicited LH release. Exposure to another male did not trigger LH release. Males released LH when allowed physical contact with an anesthetized female, but not when separated from a normally active female, suggesting that tactile or nonvolatile chemosensory stimuli elicit LH release. Urine and secretions collected from the vagina as well as oral, midventral, perineal, and rectal glands, elicited marked behavioral responses in male P. sungorus. Despite these behavioral responses, only feces from females elicited LH release in males. Males released LH in response to feces extracted from the rectum and to cotton swabs that had been rubbed against the rectal mucosa, suggesting that a component of rectal secretions may trigger LH release in male Siberian hamsters. Taken together, these data and previous data from our laboratory indicate that both the production of and the response to a pheromone that triggers the selective release of LH is regulated by day length.