Detection of Successful and Unsuccessful Pregnancies in Mice within Hours of Pairing through Frequency Analysis of High Temporal Resolution Core Body Temperature Data
Abstract:Many controllable factors negatively impact fetal development, underscoring the importance of early pregnancy detection and identification of events that reliably predict potential complications. Clinically, core body temperature (CBT) is used to aid family planning and pregnancy detection. However, such temperature data typically are gathered in single, daily measurements. In animal studies, interventions or cell/tissue harvesting at defined stages of fetal development are arduous, requiring timed mating by t… Show more
“…This may be achieved simultaneously by reducing estrogen production [36]. Such effects are only opposite to the already known role of progesterone in maintaining both pregnancy and the elevated T b that characterizes the first period of gestation [31,[37][38][39]. We speculate that progesterone and estrogen act as metabolic signals integrating nutrient and temperature homeostasis and reproduction.…”
During calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (T b ) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring T b of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of T b during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of T b and energy expenditure when nutrient availability is scarce.
“…This may be achieved simultaneously by reducing estrogen production [36]. Such effects are only opposite to the already known role of progesterone in maintaining both pregnancy and the elevated T b that characterizes the first period of gestation [31,[37][38][39]. We speculate that progesterone and estrogen act as metabolic signals integrating nutrient and temperature homeostasis and reproduction.…”
During calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (T b ) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring T b of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of T b during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of T b and energy expenditure when nutrient availability is scarce.
“…1. A subset of Mini Mitter temperature and activity data from dams were communicated in a previous report 40 . All experiments were carried out in compliance with the NIH guide for the care and use of laboratory animals and in accordance with protocols approved by the Animal Care and Use Committee at The University of California, Berkeley.Figure 1Experimental outline.…”
Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.
“…This temperature dip at ZGA may be beneficial for the chromatin to become less condensed and thus more mixed. Researchers did find that an ultimately-successful pregnancy is characterized by significantly more min/day of relative low CBT (core body temperature) in the second day after mouse pairing which rightly correspond to ZGA, than for pregnancies which subsequently terminated prematurely 30 .…”
Section: Possible Factors Influencing Phase Separationmentioning
confidence: 99%
“…As is widely known, implantation dip is effective in detecting pregnancy in humans 31 . It has been found that continuous BBT measurement reliably allows for the earliest and most accurate detection of pregnancy 30 . These observations give rise the possibility that temperature shifts are closely coupled with large scale change of chromatin structural segregation during embryonic development.…”
Section: Possible Factors Influencing Phase Separationmentioning
Chromatin undergoes drastic organization and epigenetic reprogramming during embryonic development in mammals. However, the relationship among global structural change, epigenetic reprogramming, and functional implementation is largely unknown.Based on the analysis of latest published Hi-C data of post-implantation stages, we present a consistent view of the chromatin structural change and the corresponding sequence dependence. Two types of sequentially, genetically and transcriptionally distinct domains, forests and prairies, show systematic and overall increase of spatial segregation during embryonic development, but with notable mixing occurring at two stages, ZGA and implantation. The segregation level change largely coincides with the change of genetic and epigenetic properties. Detailed gene functions in specific phase-changing domains during implantation were analyzed, based on which a possible mechanism of functional realization during implantation was proposed. Interestingly, body temperature changes coincide with the change in chromatin segregation, implying that temperature is a possible factor influencing global chromatin structure.
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