House females continuously with the sire, or house pregnant females together, or house a pregnant female with a non-pregnant female. Indeed, those few studies on sleep/wakefulness in female mice did show sex differences in sleep [16–18]. My mouse is pregnant and lives in a cage with 2 other females and 1 male. Total time, episode duration, episode number, EEG power density, and δ density of wild-type and PAH mice were compared during the course of pregnancy using one-way repeated measures ANOVA (analysis of variance) followed by post hoc Tukey’s test. (A–C) Total time spent in wake (A), wake episode duration (B), and wake episode number (C) before, during early and mid pregnancy, and postpartum in PAH mice. Hormonal changes underlie the first component to appear in the pregnant mouse female, nest building; however the sound of pups can also induce nest … she mated with a male from the pet store cage not mine. Tsukuba hypertensive mice showed a normal time spent in wakefulness and NREM sleep and a decreased total REM sleep time. Thus, only when human renin exits, human angiotensinogen is processed into angiotensin I. Using the mouse model, we examined autistic-like behaviors in greater detail, and additionally explored whether diet supplementation with docosahexaenoic acid (DHA) may mitigate the behavioral changes. Pregnant does will exhibit increased nesting behavior as the day of kindling approaches. 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During the dark phase, the duration of the NREMS episode during late pregnancy was significantly shorter than that before and during early pregnancy (F = 3.456, df = 4, p = .020; Figure 2E). A few months ago I bought a pregnant mouse, she had 9 beautiful babies, but I kept the really cute ones and I left them with mom longer than I should've, my mistake.. 2 male babies were left with mom for 6 weeks or so and then I realized they can inbreed so I immediately separated them and now the mother seems to be getting round again, I weighed her on the kitchen … The daily time spent in wakefulness decreased and the total NREMS time increased during late pregnancy, primarily reflecting increased NREMS during the dark phase, consistent with the long NREMS in pregnant rats [40, 41]. All PAH mice examined herein showed disruption of the BBB, as assessed by the intravenous injection of Evans blue dye during late pregnancy. Adopting 6 Mice (Vlog #5) - Duration: 6:59. (A) Representative 8-s EEG and EMG during wake, NREMS, and REMS during mid and late pregnancy and postpartum in a wild-type mouse. Olmesartan-administered PAH mice did not show general slowing of EEG. Published by Oxford University Press on behalf of the Sleep Research Society. (C–E) Total time spent in REMS (C), REMS episode duration (D), and REMS episode number (E) in nonpregnant PAH mice, olmesartan-administered PAH mice, and THM. Watch for nest-building behavior. However, this interpretation could be too simple since progesterone has also been reported to reduce wakefulness [51]. Human renin cannot process murine angiotensinogen, whereas mouse renin cannot cleave human angiotensinogen into angiotensin I. Thus, increased estrogen and progesterone during pregnancy may work to enhance wakefulness. Maternal interactions have implications in the physiological, psychological, and social development or mice and some of these effects remain into adulthood. PAH mice showed normal REMS characterized by θ wave and muscle atonia during late pregnancy, but the total REMS time drastically decreased compared with PAH mice during mid pregnancy and pregnant wild-type mice. One of the first steps in preventing adult fish to eat baby platies is to know how to recognize the signs of pregnancy and prepare the aquarium for the time the female platy will give birth. PAH mice utilize the “species barrier” between humans and mice in terms of angiotensinogen processing by renin. A playful chase is usually also a quieter chase; mice in a squabble tend to be more vocal. 2. We observed multiple and very light Evans blue leakages ranging in diameter from less than 0.4 mm to larger than 2 mm in the cerebral cortex and cerebellum in all PAH mice as reported in acute hypertensive rats [32], but did not find any leakage in normotensive control mice during late pregnancy (Figure 4E). Evans blue (WAKO, Japan) was dissolved to 2% (wt/vol) in 0.9% NaCl and passed through a 0.45 μm PES syringe filter (Starlab Scientific). For NREMS, power density at 4 Hz during late pregnancy was higher than that before pregnancy and during early pregnancy (F = 13.384, df = 4, p < .0001; Figure 3B). Telephone: 81-29-853-3301; Fax: 81-29-853-5735; E-mail: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, Alterations in sleep during pregnancy and postpartum: a review of 30 years of research, Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes, Sleep in women across the life cycle from adulthood through menopause, Sex differences in sleep: impact of biological sex and sex steroids, Sleep, rhythms and women’s mood. ... but just in case keep an eye out for any mean behavior toward the pregnant mouse and her … EEG or EMG was continuously recorded from PD0 through the postpartum period. She may be more likely to abandon or even cannibalize her babies. Four hours of intra-abdominal hypertension resulted in the leakage of Evans blue dye into the brain parenchyma, which was not observed 1 hr after release from abdominal hypertension [61]. Mice also can jump 13 inches high and can run along wires, cables, and ropes. Thus, PAH mice exhibit a pathophysiologic mechanism similar to human eclampsia during late pregnancy. I took her to the vet a couple of days ago and they said she looked healthy (that was when we found out she was pregnant.) That’s where the similarities between the lovable adolescent and the less-than-adorable house mouse end. Angiotensin II is a major factor inducing hypertension in the renin–angiotensin–aldosterone system [56]. The duration of the REMS episode decreased during mid and late pregnancy and postpartum compared with that before pregnancy (F = 13.474, df = 4, p < .0001; Figure 2H). INTRACELLULAR SIGNALING TO BEHAVIOR Benjamin Jurek and Inga D. Neumann Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Regensburg, Germany L Jurek B, Neumann ID. Fee is pregnant! The total REMS time of female THM was shorter than that of female wild-type mice (Figure 8G). (B) Power density during NREMS before, during, and after pregnancy. (B) δ-Densities of all epochs of nonpregnant PAH (normotensive) mice (n = 6), PAH mice (n = 6), and olmesartan-administered PAH mice (n = 5) during late pregnancy. Pregnancy is thought by so many people to be a time of happiness and excitement but the reality for most women is that pregnancy is a mixture of ups, downs and other extreme emotions. This dosage of olmesartan decreases the systolic blood pressure of PAH mice to approximately 120 mm Hg [26, 27]. Pups born to mothers exposed to fluoxetine during pregnancy make fewer and briefer squeaks than those born to mothers who had no exposure to the drug, the new study found. Food and water were delivered ad libitum. The EEG power density in each frequency bin was expressed as a percentage of the mean total EEG power over all frequency bins and sleep/wake states. Five THM and eight wild-type mice. It will fall out within hours and dissolves in a days time. However, do not add mice to a cage just a … (D) NREMS δ density before, during early and mid pregnancy, and postpartum. After mice mate a white plug forms in the female mouse's are, which prevents other males from mating with her. Sleep/wakefulness was analyzed as previously described with some modifications [35]. The angiotensin II receptors, An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation, Electroencephalography during normotensive and hypertensive pregnancy: a systematic review, Disruption of the blood-brain barrier in cerebrum and brain stem during acute hypertension, Intra-abdominal hypertension causes reversible blood-brain barrier disruption, Tissue-specific expression of the human renin gene in transgenic mice, Expression of the human angiotensinogen gene in transgenic mice and transfected cells, The brain renin-angiotensin system: location and physiological roles, The brain renin-angiotensin system: a diversity of functions and implications for CNS diseases, Impaired placental neovascularization in mice with pregnancy-associated hypertension, Oxidative stress and cerebral endothelial cells: regulation of the blood-brain-barrier and antioxidant based interventions, Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes. https://secureservercdn.net/198.71.233.5/712.919.myftpupload.com/wp-content/uploads/2016/06/maternal-video.mp4. Because of these changes, we could not determine wakefulness or NREMS for many epochs. These findings are consistent with previous reports on pregnant humans and rats [42]. Maternal behavior can be broken down into several categories such as: birth behavior, care of infants, suckling behavior, human interaction, and also negative maternal behavior. The data are presented as the mean ± SEM. REMS is characterized by θ (6–9 Hz)-dominant EEG and low amplitude of EMG. (C) Power density during REMS before, during, and after pregnancy. Does Investing in Low-income Urban Neighborhoods Improve Sleep? Neuroimaging studies of eclampsia patients revealed posterior reversible encephalopathy syndrome, which refers to reversible vasogenic cerebral edema in the posterior region of the cerebral cortex accompanied by acute neuropsychiatric symptoms [28–31]. The data from individual mice are presented as the group mean ± SEM. MY is a former Investigator of the Howard Hughes Medical Institute. (G–I) Total time spent in REM sleep (REMS) (G), REMS episode duration (H), and REMS episode number (I) before, during early and mid pregnancy, and postpartum in PAH mice. By using optogenetic and pharmacogenetic approaches, the understanding of neural circuitries regulating sleep/wake behaviors has rapidly progressed [12]. Mice are only pregnant for 21 days. The present study showed that PAH mice exhibited markedly abnormal vigilance states with a generalized slowing of EEG during late pregnancy. An increased total REMS during postpartum was observed during the light phase (F = 11.141, df = 3, p = .0008; Figure 5G), but not during the dark phase. However, behavior of the offspring was altered. (D) Enlarged spike-and-wave discharges indicated in (B and C). We also examined sleep/wake behaviors in an animal model of preeclampsia, pregnancy-associated hypertensive (PAH) mice, in which increased angiotensin causes hypertension. (B) Representative daily EEG spectrogram during mid and late pregnancy and postpartum in a wild-type mouse. After delivery, the daily total wake time lengthened to levels similar to those before pregnancy. Periodic discharges of EEG during late pregnancy in PAH mice. There was no difference in the NREMS episode duration (Figure 8E) or the NREMS episode number (Figure 8F). Total REMS time, REMS episode duration, and REM episode number of THM were similar to those of olmesartan-administered PAH mice (Figure 7C, D, and E). Mice are suitable model species for examining sleep/wakefulness during pregnancy because they have a gestation period of less than 3 weeks. Since the amino acid sequence of angiotensin I is the same between human and mouse, angiotensin I in mice is subsequently processed into angiotensin II via the removal of two amino acids at the carboxyl terminus by angiotensin-converting enzyme [25], resulting in high blood pressure. The same is true of laboratory mice. © Sleep Research Society 2017. Consistently, receptors for estrogen are abundant in the preoptic area, which is involved in sleep regulation [50]. A water gel pack (Napa Nector, 8 oz., System Engineering Lab Group Inc.) was used for a water source because this pack allows both pregnant wild-type and PAH mice to intake water easily. The EEG or EMG signaling and daily EEG spectrogram of olmesartan-administered PAH mice did not show the abnormalities (Figure 7A) observed in PAH mice (Figure 1D). For group comparisons among PAH, olmesartan-administered PAH, and THM, total δ density and REMS parameters were analyzed using one-way ANOVA followed by post hoc Tukey’s test. However in captivity, it is considered a maladaptive behavior. In parallel, the spontaneous activities of PAH mice increased, with a clear resting-active pattern consistent with the light-dark phases. The male if present, may also participate in caring for pups (Weber & Olsson, 2008). Estrogen and progesterone generally increase wakefulness and decrease sleep, as indicated by the increased wakefulness of ovariectomized mice replaced with estradiol alone or with both estradiol and progesterone [4, 18, 46–49]. Bokil H, Andrews P, Kulkarni JE, Mehta S, Mitra PP. Typically, periodic spike-and-wave discharges that were clearly different from background EEG activity occurred during the NREMS-like state and accompanied phasic EMG activities with jerky body movements (video in Supplementary Material), which typically lasted 10–15 min and repeated 4–6 times during the 24-hr period. After recovery from anesthesia, the mice were housed individually and tethered to a counterbalanced arm (Instech Laboratories) that enabled the free movement and exerted minimal weight. However, blood pressures higher than the upper limit of cerebral vascular autoregulation can lead to disruption of the BBB and vasogenic edema, eventually resulting in hypertensive encephalopathy [39]. Surprisingly, postpartum PAH mice quickly recovered from the general slowing of EEG and had a normal time spent in wakefulness and NREMS. There was no difference in the wake episode duration (Figure 5B) and wake episode number (Figure 5C). (G–I) Total time spent in REMS (G), REMS episode duration (H), and REMS episode number (I) before, during, and after pregnancy. The day of vaginal plug detected was designated pregnant day 0. n = 8; *p < .05. Mouse Behaviour Mouse Behaviour In The Wild: Mice in the wild are very territorial. **p < .01, ***p < .001. A doe giving birth should never be disturbed. PAH mice exhibited a general slowing of EEG during late pregnancy and subsequently returned to apparently normal sleep/wakefulness after delivery. Olmesartan-administered PAH mice showed a REMS episode duration similar to PAH mice (Figure 7D) and increased numbers of REMS episodes (F = 25.613, df = 2, p < .0001, Figure 7E). Fragmented sleep may be due to spontaneous movements of the embryos in the uterus and/or the pressure of the growing uterus on neighboring tissues and organs. ISBN 0-87969-574-9. Although the number of REMS episodes was similar among pregnancy groups for 24 hr and during the light phase, the number of REMS episodes during the dark phase was larger during late pregnancy compared with that before pregnancy (F = 3.625, df = 4, p = .017; Figure 2I). Pregnancy affected REMS differently from wakefulness and NREMS. Resident Physician in Cardio-Thoracic and Vascular Surgery. Identify the sex of your hamster. One-way ANOVA followed by Tukey’s test. Before pregnancy, the daily total wake time of female mice was 868 ± 29.2 min, consistent with a previous report and much longer than that of male mice [38]. Importantly, the sleep/wake behaviors of postpartum mice were similar to nonpregnant mice, despite lactation and increased prolactin and oxytocin. Thus, the acute and severe increase in blood pressure may solely be responsible for the BBB disruption in PAH mice and subsequently lead to abnormal sleep/wake behaviors. Strain differences have been demonstrated in behavior such as nest building and nursing (Weber & Olsson, 2008). EEGs and sleep/wakefulness of olmesartan-administered PAH mice. Do they make noise? We thank all Yanagisawa/Funato lab and IIIS members for discussion and comments on this manuscript and Go Taniguchi for his comments on spike-wave seizures. If your cage has sawdust, dirt or other pliable material, watch to see if she uses it to build a nest for her young. There was no difference in the wake episode duration (Figure 8B) or the wake episode number (Figure 8C). Takahashi S, Fukamizu A, Hasegawa Tet al. As an animal model of preeclampsia, pregnancy-associated hypertensive (PAH) mice have been developed by crossing female mice carrying the human angiotensinogen transgene with male mice carrying the human renin transgene [9]. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Mice that showed multiple altered parameters in wakefulness, NREMS, and REMS during late pregnancy quickly returned to normal sleep/wakefulness, excluding the decreased episode duration of wakefulness and REMS. Estrogen and progesterone increase as pregnancy progresses and then abruptly decrease after parturition [45]. Consistent with abnormal placentation and increased secretion of angiogenic factors in human preeclampsia [21], PAH mice exhibit abnormal placental angiogenesis and intrauterine growth retardation [57, 66], which may increase humoral factors and reactive oxygen species to disrupt the BBB [67]. Your comment will be reviewed and published at the journal's discretion. A general slowing of EEG in PAH mice during late pregnancy was confirmed by the high total δ density during late pregnancy compared with that during mid pregnancy (Figure 4A). Since there were many epochs that we could not properly classify into wake or NREMS during late pregnancy, we evaluated the sleep/wakefulness of PAH mice except for those in late pregnancy. The brain was removed and fixed in 4% paraformaldehyde/phosphate-buffered saline overnight at 4°C. Since we unequivocally identified REMS in PAH mice during late pregnancy based on the appearance of the θ wave (6–9 Hz) and muscle atonia (Figure 1C), we examined how the administration of olmesartan affects REMS in PAH mice. In most cases, the mice gave birth on day 19. There is no known animal model for eclampsia, although there have been pharmacological and genetic interventions to develop an animal model for preeclampsia [53–55], including PAH mice. And in this video, I’m gonna teach you some stuff about pregnant mice. Sleep is altered during pregnancy, and different sleep disturbances are associated with each trimester, likely reflecting a wide range of physiological and hormonal changes [1–5]. Total REMS time was not significantly changed before, during, and after pregnancy (Figure 2G). The World Health Organization Multicounty Survey reported that preeclampsia and eclampsia develop in 2%–3% and 0.3% of pregnancies, respectively [24]. Aggressive behavior seems to be related to gestation in the female mouse. Haruna Komiya, MD, Chika Miyoshi, PhD, Kanako Iwasaki, BSc, Noriko Hotta-Hirashima, MS, Aya Ikkyu, MS, Satomi Kanno, Takato Honda, BSc, Masahiko Gosho, PhD, Hiromi Hamada, MD, PhD, Toyomi Satoh, MD, PhD, Akiyoshi Fukamizu, PhD, Hiromasa Funato, MD, PhD, Masashi Yanagisawa, MD, PhD, Sleep/Wake Behaviors in Mice During Pregnancy and Pregnancy-Associated Hypertensive Mice, Sleep, Volume 41, Issue 3, March 2018, zsx209, https://doi.org/10.1093/sleep/zsx209. They can stand on the hind legs, as well, and are supported by the tail, which also provides balance while in motion. Analyses were carried out using two-sided tests and a statistical significance level of 0.05. n = 6; *p < .05. However, postpartum mice showed significantly longer total wake time during the light phase than before pregnancy (F = 3.271, df = 4, p = .025; Figure 2A). Hormonal changes underlie the first component to appear in the pregnant mouse female, nest building; however the sound of pups can also induce nest building in non-pregnant nulliparious (virgin) females. Each electrode has four electrode pins and two wires. We also observed that half of the PAH mice showed spike-and-wave discharges during late pregnancy, based on EEG or EMG recording supplemented with video recording. Pregnant Mouse Behavior? In humans and other mammals, sleep is altered during pregnancy. In this study, we examined sleep/wakefulness in female C57BL/6 mice during pregnancy. It is important to mention first that the mother rat may not … Physiol Rev 98: 1805–1908, 2018. In humans and other mammals, sleep is altered during pregnancy. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Youssef AM, Hamidian Jahromi A, Vijay CG, Granger DN, Alexander JS. To evaluate the validity of PAH mice as a model of eclampsia, further studies using magnesium sulfate, the most potent anticonvulsant for eclampsia patients [22], may be necessary. Rapid eye movement (REM) sleep time did not change during the course of pregnancy. Like many pregnant women, Leigh Llemit didn't have appetite on her first 2 months of pregnancy, but turned into a voracious eater once past that stage. As a normotensive control, we used pregnant human angiotensinogen transgenic mice mated with male human angiotensin transgenic mice. If she doesn't care for them and they are less than 10 days of age, it is extremely difficult to save the babies. Unfortunately, if you got a pregnant mouse from the pet store she may be quite young and may not have the best mothering abilities. Similarly, the most commonly observed EEG abnormality in human eclampsia is generalized or focal slowing of EEG [28, 58, 59], and this abnormal EEG normalizes after the release from hypertension [59]. Thus, an increased NREMS episode number may contribute to increased time spent in NREMS by overcoming the short NREMS episode duration. A short REMS episode duration was recognized from mid pregnancy through postpartum. At 8–12 weeks of age (19–23 g), female wild-type, THM, and PAH mice were anesthetized using isoflurane (3%–4% for induction and 1%–2% for maintenance). The male mouse has a larger territory than a female mouse. The number of NREMS episodes during late pregnancy was higher than that during any other periods during both light phase (F = 4.795, df = 4, p = .004) and dark phase (F = 8.697, df = 4, p < .0001; Figure 2F). For postpartum, we evaluated the third and fourth days after delivery because sleep/wake behaviors during the first 2 days after delivery varied widely depending on the time of delivery and the number of pups. An acute increase in arterial blood pressure by 80 mm Hg disrupts the BBB integrity in rats [60]. Although we did not examine the fertility rate of THM in detail, we conjecture that chronic hypertension or enhanced renin–angiotensin system may decrease the fertility of THM. To average the possible variability in sleep during the estrous cycle, we analyzed for 4 consecutive days to assess sleep/wake behaviors before pregnancy. (A) δ-Densities of all epochs during mid, late, and after pregnancy. However, no studies have been conducted on sleep/wakefulness during pregnancy in mice. Reference: Nagy A, Gertsenstein M, Vintersten K and Behringer R. 2003. We further examined the EEG power spectrum of PAH mice, except for late pregnancy. One hour later, the mice were transcardially perfused with cold phosphate-buffered saline and then 4% paraformaldehyde/phosphate-buffered saline. (D–F) Total time spent in NREM sleep (NREMS) (D), NREMS episode duration (E), and NREMS episode number (F). Gabriel Goh 26,679 views. All analyses were performed using SPSS software version 22 (IBM, Chicago, IL). The total NREMS time during the light phase was similar to that before, during, and after pregnancy (Figure 2D). They love being pregnant and don’t appear to have problems adjusting at all. Female C57BL/6J mice (CLEA Japan) were used in this study. During previous experiments pregnant mice were presented daily with an intruder, alternately male and female. Thus, an increased number of REMS episodes contributes to the increased total REMS time of olmesartan-administered PAH mice. Sleep/wakefulness during late pregnancy was also characterized by frequent switches between wakefulness and NREMS, resulting in an increased episode number and short episode duration of both wakefulness and NREMS during both the light and dark phases. Continued progress in genetic engineering, including genome editing, has provided rapid progress in the genetics of sleep [11]. This study also proposes that PAH mice may be an animal model of eclampsia. (A) Representative daily EEG spectrogram during late pregnancy in a PAH mouse that was administered olmesartan. The effect of chronic intermittent hypoxia in cardiovascular gene expression is modulated by age in a mice model of sleep apnea.