Menstrual cycle and some other related aspects of Japanese monkeys (Macaca fuscata)

The menstrual cycle and some other related aspects of Japanese monkeys (Macaca fuscata) were dealt with in this paper. Almost all the monkeys had regular menstrual cycles only in the mating season, and had no menstrual cycles, or only irregular ones, in the non-mating season. The average length of the menstrual cycle in the mating season was 26.3 ±5.4 days. Many monkeys had a tendency to have their own individual and relatively regular cycles. Ninety out of 108 monkeys kept in the air-conditioned quarters for five years showed “periodical changes” essentially coincident with the changes of outdoor season, and this fact suggests that the rhythm of the seasonal change of Japanese monkeys remains for a relatively long period even if the monkeys are kept in air-conditioned quarters where room temperature and lighting are kept constant throughout the year. Vaginal smear, cervical mucus, sexual skin, etc. were observed in relation to ovulation. These characters showed cyclic changes with menstrual cycles in about half of all cases observed, but ovulation occurred even in the cases in which no cyclic change was observed. Therefore, it was not necessarily easy to estimate the ovulation by observing these characters.     

Role of estrogen receptors in pro-oxidative and anti-oxidative actions of estrogens: A perspective

Background

Estrogens are steroid hormones responsible for the primary and secondary sexual characteristics in females. While pre-menopausal women use estrogens as the main constituents of contraceptive pills, post-menopausal women use the same for Hormone Replacement Therapy. Estrogens produce reactive oxygen species by increasing mitochondrial activity and redox cycling of estrogen metabolites. The phenolic hydroxyl group present at the C3 position of the A ring of estrogens can get oxidized either by accepting an electron or by losing a proton. Thus, estrogens might act as pro-oxidant in some settings, resulting in complicated non-communicable diseases, namely, cancer and cardiovascular disorders. However, in some other settings the phenolic hydroxyl group of estrogens may be responsible for the anti-oxidative beneficial functions and thus protect against cardiovascular and neurodegenerative diseases.

Scope of review

To date, no single review article has mentioned the implication of estrogen receptors in both the pro-oxidative and anti-oxidative actions of estrogens.

Major conclusion

The controversial role of estrogens as pro-oxidant or anti-oxidant is largely dependent on cell types, ratio of different types of estrogen receptors present in a particular cell and context specificity of the estrogen hormone responses. Both pro-oxidant and anti-oxidant effects of estrogens might involve different estrogen receptors that can have either genomic or non-genomic action to manifest further hormonal response.

General significance

This review highlights the role of estrogen receptors in the pro-oxidative and anti-oxidative actions of estrogens with special emphasis on neuronal cells.     

Relationships between ovarian morphology, vaginal cytology, serum progesterone, and urinary immunoreactive pregnanediol during the menstrual cycle of the cynomolgus monkey

Three different indices of ovulation and luteal activity were studied in eight regularly cycling cynomolgus monkeys. A significant relation between changes in serum progesterone and immunoreactive pregnanediol (I-PD) in urine was obtained. The occurrence of ovulation could be determined reliably from a change in the ratio of cornified to basal epithelial cells in vaginal smears, and luteal activity could be assessed reliably from daily measurements of urinary pregnanediol. The time of ovulation could be defined more precisely by daily I-PD radioimmunoassays than by the vaginal smear pattern. Measurements of I-PD also have the advantage of ease and noninvasiveness over serum progesterone determinations. More detailed information about changes in hormonal activities could not be obtained reproducibly from thorough examination of cell types in vaginal smears.     

The menstrual cycle and its effect on behaviour in the Talapoin monkey (Miopithecus talapoin)

The menstrual cycles of 14 captive Talapoin monkeys ( Miopithecus talapoin ) were studied by making serial observations on the vaginal smears and sexual skin swellings for up to 15 months. Twelve of these females menstruated and the mean duration of their cycle was32–9 days (95% confidence limits 28.0-37.7). The corresponding value for the seven most regular females was 33.0 days (29.1-36.8). There were rhythmic changes in the vaginal smears and sexual skin during the menstrual cycle. Maximum cornification of the smears and maximum sexual skin swelling were observed at midcycle; the sexual skin deflated and the smear became less cornified during the luteal phase. The follicular phase—i.e. from menstruation to maximum skin swelling lasted 20.4 days with a wide distribution, in contrast to the mean duration of the luteal phase (13.7 days) which showed a pronounced peak at 14 days. The menstrual cycle of the talapoin thus resembles those of certain other Old World monkeys that exhibit perineal sexual skin swelling.
Sexual behaviour of the male and female was maximal near the female's midcycle and minimal during the luteal phase, with intermediate values in the follicular phase. The males were most aggressive towards other females of the group when one female was at midcycle; there were no consistent changes in aggression between the male and the female herself. The number of times one animal looks at another (a characteristic behaviour pattern in talapoins) was measured and occurred most often at midcycle, but other preliminary observations indicated a more pronounced correlation between this behaviour pattern and an animal's position in the hierarchy.     

A review of sexual initiating behavior by male and female cynomolgus monkeys and some species comparisons

The sexual initiating behavior of male and female cynomolgus monkeys (Macaca fascicularis) observed during standard laboratory tests is reviewed and compared with that of rhesus monkeys (M. mulatta) observed under identical conditions. Species differences in sexual behavior are related here to differences in habitat, sexual dimorphism, and the dominance gradient between the sexes. Compared with rhesus monkeys, cynomolgus monkeys appear to be more arboreal, less sexually dimorphic, and have a smaller dominance gradient between the sexes. They exhibit a facultative single-mount copulatory pattern rather than the serial mount pattern of the rhesus monkey. Female cynomolgus monkeys are less dominated than rhesus females by their male partners. Direct aggression between mates is more frequent and redirected aggression occurs less often than in rhesus monkeys. These behavioral differences affect the interpretation of changes in initiation rates that occur (1) during the menstrual cycle, (2) when females are ovariectomized and given hormone replacement treatments, and (3) when males are castrated and treated with androgens. We conclude that estradiol in the female and testosterone in the male increase the sexual motivation of both the treated and the untreated partner. Valid interpretations of changes in initiation rates depend on accurate and exclusive definitions of behavior and on a consideration of the behavioral context in which they are made.     

Learning and perception of oddity problems by lemurs and seven species of monkey

Eight nonhuman primate species were compared in three experiments utilizing the oddity paradigm. The sample included 4 lemurs (Lemur catta), 26 Old World Monkeys (Macaca mulatta, M. nemestrina, M. speciosa, andCercopithecus nictitans) and 21 New World Monkeys (Cebus apella, Lagothrix humboldti andSaimiri sciurea). EveryS was first trained 60 days on “outside oddity” problems. Next,Ss solved “outside” oddity problems constituted from two short and two tall cylinders, and were tested for their perception of oddity withDavis andMcDonald's (1962) technique of varying the height of the centerplaced but nonreinforced stimulus. In the final experiment,Ss were given ambiguous oddity problems that could be solved either for form or color cues, andEs recorded preference. Cebus and woolly monkeys formed oddity learning sets as well as or better than any of the Macaque monkeys, but relatively poor performances were made by squirrel monkeys, spotnose monkeys, and lemurs. Woolly monkeys were outstandingly accurate in their perception of oddity based on changing stimulus height, no other species approaching them in this skill. Old World Monkeys were much more likely than New World Monkeys to use color as a cue.     

First postpartum estrus and pregnancy in the female collared peccary (Tayassu tajacu) from the amazon

The onset of sexual cycle postpartum was described in the collared peccary (Tayassu tajacu). Serum progesterone and 17beta-estradiol profiles, vaginal smears and external genitalia were analyzed in 20 animals housed with their piglets during the first postpartum month. The appearance of external genitalia showed no variation in any of the females: a shallow, reddish vulva, and vaginal mucus were constant features throughout the study. Based on hormonal profiles and vaginal smear cell patterns, 16 (80%) of the 20 peccaries showed signs of estrus and were considered cycling. The remaining four females (20%) did no show signs of estrus confirmed by low levels of progesterone (0.9+/-0.4 ng/mL) during the first postpartum month. In the cycling peccaries, a serum 17beta-estradiol peak (53.4+/-8.1 pg/mL) was observed on Day 7+/-1 postpartum, along with a linear increase in progesterone concentration from 3 (4.3+/-2.6 ng/mL) to 11 (30.8+/-4.9 ng/mL) days after this estradiol peak. Proportions of the different cells of the vaginal epithelium also changed in these females: superficial plus intermediate cells amounted to 76% of the cell total between Days 6 and 9 postpartum, corresponding to the estradiol peak. Nine (56%) of the 16 cycling females mated, indicated by the presence of sperm cells in their vaginal smears, and 6 (67%) became pregnant, reaching term. Non-pregnant cycling females (n=10) showed a steady decrease in serum progesterone concentration from 11 to 23 days after the estradiol peak, when basal levels were attained and a new estradiol peak registered, indicating the resumption of cyclicity in these females. The time interval between the two estradiol peaks was 23.5+/-2.1 days in these females. In pregnant females, progesterone concentrations continued to rise to levels of 60 ng/mL (n=6) 23 days after mating. These findings indicate that the lactating collared peccary female can become cycling and fertile during the early postpartum period, and that a predominance of superficial plus intermediate vaginal cells can be taken as the first sign of estrus.     

Evidence of endoplasmic reticulum stress and liver inflammation in the American mink Neovison vison with benign hepatic steatosis

We investigated the presence of inflammatory signs in the progression of fatty liver disease induced by fasting. Sixty standard black American mink (Neovison vison) were fasted for 0, 1, 3, 5, or 7 days and one group for 7 days followed by re-feeding for 28 days. Liver sections were evaluated histologically and liver mRNA levels indicating endoplasmic reticulum (ER) stress, adipogenic transformation, and inflammation were assessed by quantitative real-time PCR. After 3 days of fasting, the mink had developed moderate liver steatosis. Increased hyaluronan reactivity in lymphocytic foci but no Mallory–Denk bodies were seen in livers of the mink fasted for 5–7 days. Up-regulation of glucose-regulated protein, 78 kDa was observed on day 7 indicating ER stress, especially in the females. Liver lipoprotein lipase and monocyte chemoattractant protein 1 mRNA levels increased in response to 5–7 days of food deprivation, while tumor necrosis factor α (TNF-α) was the highest in the mink fasted for 5 days. The expression of the genes of interest, except for TNF-α, correlated with each other and with the liver fat content. The mRNA levels were found to change more rapidly below n-3/n-6 polyunsaturated fatty acid ratio threshold of 0.15. Following re-feeding, hepatocyte morphology and mRNA abundance returned to pre-fasting levels. Within the studied timeframe, evidence for ER stress, adipogenic transformation, and liver inflammation suggested incipient transition from steatosis to steatohepatitis with potential for development of more severe liver disease. This may present a possibility to influence disease progression before histologically observable steatohepatitis.     

A field study of the pigtail monkey (Macaca nemestrina)

A field study of the pigtail monkey (Macaca nemestrina) was conducted in Malaysia. An initial six month survey revealed a badly disturbed, diminishing population. Intensive observation required prolonged extensive habituation efforts including a modified form of provisionization and the use of a trained captive pigtail monkey. The pigtail monkey was found to be an arboreal deep forest animal which, nonetheless, came to the ground more often than any other monkey in the forests of Malaya. Responses observed in the natural habitat could not be differentiated from those seen in captive groups; but response frequencies differed. Social patterns observed were similar to those seen in other macaques but differed notably from those seen in sympatric leaf monkeys. Travel patterns, feeding, agonistic responses, sexual behavior, play and other responses are described and discussed.     

Maturation value as an indicator of the serum estrogen concentration during treatment with gonadotropins

Smears were taken each day from the middle third of the lateral vaginal wall of 14 infertile women being treated with daily intramuscular injections of human menopausal gonadotropins followed by human chorionic gonadotropins to induce ovulation. Each smear was stained with modified Papanicolaou stain and screened for the maturation index (MI), which was then converted to Meisel's maturation value (MV). In the 23 treatment cycles, the MV of the vaginal smears was compared to daily serum estrogen concentrations. In 7 of the 23 cycles the MV predicted a rise in serum estrogens; in 16, however, the MV did not predict the increasing serum estrogen concentrations. Although determination of the MV is inexpensive, easily obtained and rapidly performed, the cytologic examination of the vaginal epithelium cannot be used to predict the dynamic changes in serum estrogen concentrations during gonadotropin treatment.     

A comparative study of the estrogenic potential of two synthetic estrogens (mestranol and ethinylestradiol)

The purpose of this study was to establish the relative estrogenicity of ethinylestradiol and mestranol and to establish .05 and .1 mg of mestranol as standard reference preparations for the comparative study of other compounds. Patients were selected from a large group of primary amenorrhea, secondary amenorrhea, and postmenopausal women. All required hormonal replacement therapy. Patients with chromosomal abnormalities or those with diminished or abnormal response were excluded. Vaginal cytology was used as the main method for the assessment of the response. Before treatment all had either an atrophic pattern (Maturation Index = 50-50-0) or a hypertrophic pattern (MI=5-95-0) with a mean value of 10-87-3 for patients with primary amenorrhea and 18-79-3 in the other 2 groups. Patients with a proliferative intermediate cell pattern and postmenopausal women thought to have continuing endogenous estrogen activity were omitted. Ethinylestradiol or mestranol were given orally in doses of .025, .05, and .1 mg for a period of 10 days during which frequent vaginal smears were made. When cell patterns showed extremely marked cytolysis of the glycogen-containing intermediate cells and a low percentage of karyopyknotic superficial cells these patients were excluded. 40 women were finally included. The effects of estrogen on the vaginal epithelium in all 40 women after 10 days therapy were quite uniform. In those cases showing delayed regression of estrogenic effects 4 mg of chlormadinone acetate was given daily for 10 days. These patients then showed a reduction in the superficial cell percentage accompanied by a shift to the left in the maturation index such as 0-40-60 before to 0-95-5 after treatment. A few women had an insignificant reduction in the superficial cell percentages. Changes in the percentages of the intermediate type of cells were not significant. The regression was considered to be complete when the smear contained mainly small intermediate cells and parabasal cells with numerous leukocytes and some necrotic debris. Both estrogen preparations produced the same vaginal response at .05 mg doses. Tablets of .05 and .1 mg mestranol were chosen for further study. The increase in the superficial cell index to 30 (SD plus or minus 18.5) following treatment with .05 mg and the increase to 54.1 (SD plus or minus 26.7) following .1 mg have been adopted as standard vaginal responses. The term estrogenic effect used in vaginal cytology is taken to mean the local vaginal effect induced by estrogens.     

The reproductive cycle of the crab-eating macaque (Macaca fascicularis)

Characteristic changes in the menstrual cycle of the crab-eating macaque were evaluated. Cyclical changes in type and abundance of exfoliated cells in vaginal smears as well as the ferning pattern of cervical mucus were observed. These indices were useful in predicting approximate ovulation time. The cyclical changes in sexual skin swelling and/or coloration were detected only in adolescent females. Micro-sections from ovaries of autopsied animals revealed large Graafian follicle formations often rupturing by day fourteen of the cycle. Length of the menstrual cycle ranged from 26–38 days with a modal value of 28 days.This research has been supported by Ford Foundation Grant No. 710-0287.     

Relaxation of reproductive suppression in non-breeding female naked mole-rats, Heterocephalus glaber

Ninety-four non-reproductive female naked mole-rats, from seven colonies, were studied in terms of vaginal perforation, vaginal smears and urinary concentrations of oestradiol-17β and progesterone in relation to the time of parturition of the breeding female, the queen. The study concentrated mainly on the period from nine days prepartum to 13 days postpartum of 12 births. Sixty-eight percent ( n = 253) of the non-reproductive females had detectable urinary concentrations of oestradiol-17β and many of these had perforated vaginas throughout the study period. These females showed a significantly increased urinary concentration of oestradiol six days prior to parturition of the queen. In females with undetectable concentrations of oestradiol-17β, the proportion with perforated vaginas increased from six days prepartum (54%) to reach a peak on the day of parturition (92%) of the queen. Urinary progesterone-concentrations were 0.7nmol/mmol creatinine at some stage in the study period in 90% of the females and scattered short peaks or spikes were experienced by all these females, but without synchronization between the females in a colony and without any detectable correlation with the time of parturition of the queen. Maximal concentrations in some females were comparable to the values in cycling breeding females during the luteal phase, but were of a much shorter duration than in breeding females. Vaginal smears did not show clear cyclic patterns.     

Comparative Effects of Hispidulin,Genistein, and Icariin with Estrogen on Bone Tissue in Ovariectomized Rats

Icariin, Genistein, and Hispidulin have been proven to have estrogen-like and antiosteoporotic activity and can be potentially used for the treatment of osteoporosis. The present study found that Icariin, Genistein, and Hispidulin treatments, emulating estrogen, significantly contributed to bone density. Comparative effects of Icariin, Genistein, and Hispidulin with estrogen on in ovariectomized rats were investigated. Our results showed that genistein was found to have superior bone protective effects against osteoporosis among genistein, Icariin, and Hispidulin.     

Routine measurement of urinary total estrogens of the female Japanese monkey as an index for estimating the time of ovulation

The fluorometry of urinary total estrogens ofBrown et al. (1968) has been modified and successfully applied to the routine measurement of urinary estrogens in Japanese monkeys. Serial analysis during the menstrual cycle of the Japanese monkey has shown typical changes in urinary total estrogens with a distinct midcycle peak which preceded the day of ovulation by 0–2 days. The technique is valuable in an accurate estimation of the time of ovulation for successful programmed breeding of the Japanese monkey.     

Urinary zearalenone measured with ELISA as a biomarker of zearalenone exposure in pigs

The suitability to assess zearalenone (ZEA) exposure in pigs of a commercial ELISA kit for ZEA analysis in urine was tested. A daily dose of 0, 5, 10, 20 and 40 μg synthetic ZEA per kilogram BW was administered via the feed to four gilts per dose group, and after 3 and after 7 days of ZEA intake, urine samples were assayed with the ELISA which has a relative cross-reactivity of 42 % with α-zearalenol. The concentration of urinary ZEA equivalents (ZEA plus 42 % of α-zearalenol present) did not differ between day 4 and day 8 (P?=?0.50) within each dose group. The urinary ZEA equivalent/creatinine ratio was tightly correlated with ZEA intake (r?=?0.95). The urinary ZEA equivalent/creatinine values at 0 and 40 μg/kg BW were distinctly different from those of the intermediate dose levels, whereas there was some overlapping of the individual values at the dose levels 5, 10 and 20 μg/kg BW. The urinary ZEA equivalent/creatinine ratio can be used as a biomarker for ZEA exposure in pigs provided that urine samples of several animals receiving the same diet are assayed, either separately or after pooling.     

Estrogenic contributions to sexual differentiation in the female guinea pig: influences of diethylstilbestrol and tamoxifen on neural, behavioral, and ovarian development

We administered the synthetic estrogen, diethylstilbestrol (DES), or the antiestrogen, tamoxifen, to pregnant guinea pigs and observed the consequences for sexual differentiation of their female offspring. Hormones were administered during the period when treatment of fetuses with testosterone influences the development of sex-related traits (approximately Days 30 to 65 of gestation). Ovarian function, masculine and feminine sexual behavior, and the structure of a sexually dimorphic neural region in the preoptic area were assessed in adulthood in hormone-exposed animals and in oil-treated and untreated controls. Prenatal exposure to DES dipropionate (DESDP) caused masculinization and defeminization. DESDP-treated females mounted more than control females, both without hormonal stimulation and when given testosterone propionate (TP) as adults. The sexually dimorphic neural region was also masculinized in these females. In regard to defeminization, they showed delayed vaginal opening, impaired progesterone (P) production, an absence of corpora lutea, and impaired lordosis and mounting responses to estradiol benzoate (EB) and P. Prenatal treatment with tamoxifen produced a complicated pattern of results. Tamoxifen-exposed females evidenced less masculine-typical behavior, showing diminished mounting without hormonal stimulation and in response to TP. However, they also showed delayed vaginal opening, enhanced P production, and impaired mounting in response to EB and P. Their lordosis behavior and the volume of the sexually dimorphic neural region were unaffected. These results suggest that estrogens play a substantial role in sexual differentiation in the guinea pig. High levels of estrogen promote masculine-typical development, and unusually low levels may impair some aspects of both masculine-typical and feminine-typical development.     

Properties of arginase from liver of Macaca fascicularis: Comparison of normals with red blood cell arginase deficient monkeys

Deficiency of arginase (E.C. 3.5.3.1), the fifth enzyme of the urea cycle, was found in the red blood cells (RBCs) of Macaca fascicularis monkeys (<0.2 µmol arginine cleaved/g Hb/min; normal =49.2). Liver biopsies were obtained from two of these monkeys and from one monkey with normal levels of RBC arginase activity. Arginase from both groups of animals required Mn²⁺ for maximal enzyme activity and demonstrated a pH optimum of 10.2 in vitro. The activity of arginase in the livers of all three monkeys was 1.1 mmol arginine cleaved/g protein/min. The apparent K _m for arginine of arginase in the livers of the RBC-deficient monkeys was 7.4 and 5.9mm and in the normal monkey was 6.9mm. Similar patterns of heat denaturation were seen at 69 C without Mn²⁺ present and 79 C in the presence of 20mm Mn²⁺. No difference in mobility on either acidic or basic polyacrylamide gels for liver arginase from either RBC-deficient or normal monkeys was found. In addition, liver arginase from all three monkeys reacted similarly with anti-human liver arginase antibody. Liver arginases in RBC-deficient and normal monkeys were identical by ten criteria. These studies do not distinguish among several hypotheses for the genetic determination of arginase in different organs of this species and of man.     

Luteal function during the periimplantation period and requirement for estrogen for implantation and pregnancy maintenance in the non-human primate

An attempt has been made in this paper to review our present understanding of luteal function during the periimplantation period and in particular hormonal requirement for implantation and maintenance of early pregnancy in the non-human primate.In a fertile cycle thecorpus luteum is apparently rescued from luteolysis by chorionic gonadotropin secreted by the implanted blastocyst, In the bonnet monkey the serum progesterone titers during the luteal phase of a fertile cycle seems higher compared to that of nonmated cycling monkeys. This suggested that thecorpus luteum is receiving some stimulatory signal from the blastocyst even prior to implantation. The recent demonstration that human blastocyst in culture secretes into the medium human chorionic gonadotropin essentially support the above assumption. However, attempts to extend the luteal phase of cycling unmated monkeys with exogenous human chorionic gonadotropin injection has hitherto not met with complete success suggesting that there could be other than chorionic gonadotropin, additional luteal stimulatory factors the unimplanted blastocyst is secreting.Corpus luteum is the principle source of both progesterone and estrogen produced during the periimplantation period and dysruption of luteal function, brought about by either lutectomy or ovariectomy or luteinizing hormone antiserum treatment, followed by progesterone supplementation leads to maintenance of pregnancy. This has lead to questioning the need for estrogen in the maintenance of early pregnancy. Recent work using Zuclomiphene, an antiestrogen during days 5–11 of cycle in rhesus monkeys mated between day 9–14, has however, suggested that estrogen may be required for implantation. Further work is needed to arrive at an unequivocal decision regarding the need for estrogen in maintenance of early pregnancy in the primate.