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      Stressed by Maternity: Changes of Cortisol Level in Lactating Domestic Cats

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          Abstract

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          Milk feeding is the most important part of maternal care in the first weeks of the offspring’s life as it contributes to growth and development of the young, but at considerable energetic expense to the mother. One of the indicators that can be used to assess the physiological state of the female is the cortisol level relating to the stress of animals. Presumably, the more offspring there are in the litter, the higher the level of stress on the mother and, accordingly, the higher the cortisol concentrations. This study presents our data obtained in domestic cats whose litter size varied from 1 to 7 kittens. We found that the highest cortisol concentrations were observed at the peak of lactation, i.e., in 4 weeks of kittens’ life, when the offspring’s milk needs were at maximum. Moreover, during the period of offspring’s growth, the hormone level was higher in females with 1–3 kittens. In addition, cortisol concentrations in less productive cats were very high, even before mating.

          Abstract

          Lactation is the most energetically expensive component of maternal care in mammals. Increased reproductive investment can lead to physiological stress for the mothers, based on the exhaustion of energy resources and increase in glucocorticoids level. This study aimed to estimate the changes in cortisol concentrations during lactation in domestic cats and compared the differences among litter sizes. Eleven females gave birth to 27 litters, which were divided in two groups—small (1–3 kittens) and large (4–7 kittens) litters. Blood samples were collected from each female before mating, after parturition, at 4 and 8 weeks of lactation. We showed that the cortisol level in females changed significantly during lactation—the highest concentrations were observed at the peak of lactation at 4 weeks. Cortisol levels varied significantly among females but did not depend on their maternal experience. We also revealed that there were no differences in cortisol levels between females with small and large litters, but at 4 weeks of lactation, the hormone concentrations were higher in females with small litters. It is likely that these females initially invested less in reproduction, giving birth to fewer offspring.

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          Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.

          Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > -0.6). These findings suggest that maternal behavior serves to "program" hypothalamic-pituitary-adrenal responses to stress in the offspring.
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            Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum.

            The principal modulators of the hypothalamic-pituitary-adrenal (HPA) axis are corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP). Corticotropin-releasing hormone is not exclusively produced in the hypothalamus. Its presence has been demonstrated at peripheral inflammatory sites. Ovulation and luteolysis bear characteristics of an aseptic inflammation. CRH was found in the theca and stromal cells as well as in cells of the corpora lutea of human and rat ovaries. The cytoplasm of the glandular epithelial cells of the endometrium has been shown to contain CRH and the myometrium contains specific CRH receptors. It has been suggested that CRH of fetal and maternal origin regulates FasL production, thus affecting the invasion (implantation) process through a local auto-paracrine regulatory loop involving the cytotrophoblast cells. Thus, the latter may regulate their own apoptosis. During pregnancy, the plasma level of circulating maternal immunoreactive CRH increases exponentially from the first trimester of gestation due to the CRH production in the placenta, decidua, and fetal membranes. The presence in plasma and amniotic fluid of a CRH-binding protein (CRHbp) that reduces the bioactivity of circulating CRH by binding is unique to humans. Maternal pituitary ACTH secretion and plasma ACTH levels rise during pregnancy-though remaining within normal limits-paralleling the rise of plasma cortisol levels. The maternal adrenal glands during pregnancy gradually become hypertrophic. Pregnancy is a transient, but physiologic, period of hypercortisolism. The diurnal variation of plasma cortisol levels is maintained in pregnancy, probably due to the secretion of AVP from the parvicellular paraventricular nuclei. CRH is detected in the fetal hypothalamus as early as the 12th week of gestation. CRH levels in fetal plasma are 50% less than in maternal plasma. The circulating fetal CRH is almost exclusively of placental origin. The placenta secretes CRH at a slower rate in the fetal compartment. AVP is detected in some neurons of the fetal hypothalamus together with CRH. AVP is usually detectable in the human fetal neurohypophysis at 11 to 12 weeks gestation and increases over 1000-fold over the next 12 to 16 weeks. The role of fetal AVP is unclear. Labor appears to be a stimulus for AVP release by the fetus. The processing of POMC differs in the anterior and intermediate lobes of the fetal pituitary gland. Corticotropin (ACTH) is detectable by radioimmunoassay in fetal plasma at 12 weeks gestation. Concentrations are higher before 34 weeks gestation, with a significant fall in late gestation. The human fetal adrenal is enormous relative to that of the adult organ. Adrenal steroid synthesis is increased in the fetus. The major steroid produced by the fetal adrenal zone is sulfoconjugated dehydroepiandrosterone (DHEAS). The majority of cortisol present in the fetal circulation appears to be of maternal origin, at least in the nonhuman primate. The fetal adrenal uses the large amounts of progesterone supplied by the placenta to make cortisol. Another source of cortisol for the fetus is the amniotic fluid where cortisol converted from cortisone by the choriodecidua, is found. In humans, maternal plasma CRH, ACTH, and cortisol levels increase during normal labor and drop at about four days postpartum; however, maternal ACTH and cortisol levels at this stage are not correlated. In sheep, placental CRH stimulates the fetal production of ACTH, which in turn leads to a surge of fetal cortisol secretion that precipitates parturition. The 10-day-long intravenous administration of antalarmin, a CRH receptor antagonist, significantly prolonged gestation compared to the control group of animals. Thus, CRH receptor antagonism in the fetus can also delay parturition. The HPA axis during the postpartum period gradually recovers from its activated state during pregnancy. The adrenals are mildly suppressed in a way analogous to postcure Cushing's syndrome. Provocation testing has shown that hypothalamic CRH secretion is transiently suppriently suppressed at three and six weeks postpartum, normalizing at 12 weeks.
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              Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation.

              Over the past 40 years, it has been recognised that the maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations through pregnancy and lactation that might contribute to avoidance of adverse effects of stress on the mother and offspring. The extent of the global adaptations in the HPA axis has been revealed and the underlying mechanisms investigated within the last 20 years. Both basal, including the circadian rhythm, and stress-induced adrenocorticotrophic hormone and glucocorticoid secretory patterns are altered. Throughout most of pregnancy, and in lactation, these changes predominantly reflect reduced drive by the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN). An accompanying profound attenuation of HPA axis responses to a wide variety of psychological and physical stressors emerges after mid-pregnancy and persists until the end of lactation. Central to this suppression of stress responsiveness is reduced activation of the pPVN CRF neurones. This is consequent on the reduced effectiveness of the stimulation of brainstem afferents to these CRF neurones (for physical stressors) and of altered processing by limbic structures (for emotional stressors). The mechanism of reduced CRF neurone responses to physical stressors in pregnancy is the suppression of noradrenaline release in the PVN by an up-regulated endogenous opioid mechanism, which is induced by neuroactive steroid produced from progesterone. By contrast, in lactation suckling the young provides a neural stimulus that dampens the HPA axis circadian rhythm and reduces stress responses. Reduced noradrenergic input activity is involved in reduced stress responses in lactation, although central prolactin action also appears important. Such adaptations limit the adverse effects of excess glucocorticoid exposure on the foetus(es) and facilitate appropriate metabolic and immune responses.
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                Author and article information

                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                22 May 2020
                May 2020
                : 10
                : 5
                : 903
                Affiliations
                [1 ]A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 119071 Moscow, Russia; erofeevamariya@ 123456yandex.ru (M.N.E.); snaidenko@ 123456mail.ru (S.V.N.)
                [2 ]Institute of Geography, Russian Academy of Sciences, 119017 Moscow, Russia; julia.loshchagina@ 123456gmail.com
                Author notes
                Author information
                https://orcid.org/0000-0002-1996-2387
                https://orcid.org/0000-0002-8662-0723
                Article
                animals-10-00903
                10.3390/ani10050903
                7278448
                32456071
                3933878c-9f82-456b-8339-c527db202516
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 May 2020
                : 19 May 2020
                Categories
                Article

                glucocorticoids,cortisol,lactation,reproductive success,litter size,cat

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