Importance of Selected Nutrients and Additives in the Feed of Pregnant Sows for the Survival of Newborn Piglets.

This systematic review analyzed the effect of selected nutrients and additives in the feed of pregnant sows on the survival of newborn piglets. We analyzed 720 peer-reviewed publications in English in PubMed® and Web of Science®, dated July 2023 to January 2024, related to the effect of dietary supplementation with fatty acids and various percentages of protein, amino acids, and/or sources of dietary fiber on the offspring of gestating sows. While several papers evaluated the effect of nutrition on gestating sows, only a few delved into the distinct feeding strategies required at each stage of gestation to meet the NRC's nutritional requirements for maternal tissue gain and postnatal neonatal survival and growth. This body of research suggests that as gestation progresses the sow's nutritional requirements increase, as the NRC established, to satisfy their own metabolic needs and those of their fetuses. Additional research is needed to determine an optimal feeding strategy.

Alterations of learning and memory are accompanied by alterations in the expression of 5-HT receptors, glucocorticoid receptor and brain-derived neurotrophic factor in different brain regions of an animal model of depression generated by neonatally male treatment with clomipramine in male rats.

Depressive illness has been associated with impaired cognitive processes accompanied by reduced neurotrophin levels, especially brain-derived neurotrophic factor (BDNF), and dysfunctions in the hypothalamic-pituitary-adrenal (HPA) axis. In addition, depression is characterized by a decreased functioning of the serotonergic system due to changes in the activity or expression of its receptors including, most significantly, 5-HT1A, 5-HT2A, and 5-HT3 in brain regions that regulate mood, emotions, and memory, such as the prefrontal cortex, hippocampus, and amygdala. In this regard, rats treated with clomipramine (CMI) in the neonatal stage show depression-like behaviors that persist into adulthood; hence, this constitutes an adequate model of depression for exploring various molecular aspects associated with the etiology of this disorder. This, study, then, was designed to analyze the long-term effects of early postnatal exposure to CMI on the expression of 5-HT1A, 5-HT2A, and 5-HT3 receptors, as well as BDNF and GR in the following brain regions: PFC, amygdala, hippocampus, and hypothalamus, which could be related to alterations in memory and learning, as evaluated using the novel object recognition (NOR) and Morris water maze (MWM). Expression of the 5-HT1A, 5-HT2A, and 5-HT3 receptors, BDNF, and the glucocorticoid receptor (GR) was assessed by RT-qPCR in the four aforementioned brain regions, all of which play important roles in the control of memory and mood. Findings show that neonatal treatment with CMI causes alterations in memory and learning, as indicated by alterations in the results of the MWM and NOR tests. Expression of the 5-HT1A receptor increased in the hippocampus, amygdala, and hypothalamus, but decreased in the PFC, while the 5-HT2A and BDNF receptors decreased their expression in the PFC, amygdala, and hippocampus. There was no change in the expression of the 5-HT3 receptor. In addition, expression of GR in the hippocampus and PFC was low, but increased in the hypothalamus. Taken together, these data show that neonatal CMI treatment produces permanent molecular changes in brain regions related to learning and memory that could contribute to explaining the behavioral alterations observed in this model.

Effects of postnatal exposure to cadmium on male sexual incentive motivation and copulatory behavior: Estrogen and androgen receptors expression in adult brain rat.

There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1-56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -ß), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

Delay in puberty indices of Wistar rats caused by Cadmium. Focus on the redox system in reproductive organs.

Puberty is a transitional period from juvenile stage to adulthood, followed by the functional maturation of gonads and reproductive organs. This period is sensitive to environmental pollutants like cadmium (Cd), a heavy metal that represents a serious health risk. Cd is an endocrine disruptor that interferes with reproduction by causing oxidative stress in the reproductive organs, affecting the sexual function and decreasing testosterone (T) levels. However, little research has been done on the effects of Cd on puberty markers and antioxidant systems. In this study, we evaluated the effects of Cd on puberty markers: preputial separation, testes descent and T levels, and the antioxidant activity (SOD, CAT, GSH/GSSG and TAC) in the seminal vesicles, testis and epididymis. Male Wistar pups were treated with 1 mg/kg Cd or saline solution by i.p. injection from day 1 to 35; the other treatment was administrated for 49 days. At the end of treatment, the animals were sacrificed, and the tissues of interest dissected, weighed and prepared for the respective assays. Cd treated rats from birth to puberty showed a delay onset in the puberty markers and a low weight in reproductive organs. Also, Cd induced differential effects on the redox system in reproductive organs and decreased T levels, these effects played a pivotal role in the delay of puberty markers onset (testes descent and preputial separation), affecting the development and sexual maturity of the male rats.

Neuroendocrine effects of cadmium exposure on male reproductive functions.

In industrialized countries, the use of Cadmium (Cd) produces a form of anthropogenic pollution. Hence, exposure by human populations is becoming a public health problem. With a half-life of up to 40 years, cadmium is now a topic of great interest due to its role as an endocrine disruptor and its effects on male reproduction. Cd's diverse toxic mechanisms are based on its capacity to mimic divalent ions -calcium, zinc, iron- that participate in physiological processes. It alters the mitochondrial function and generates the production of free radicals that can induce apoptosis. In male reproduction, Cd alters the precise coordination of the hypothalamic-hypophysis-testis axis (HHT), resulting in the loss of testicular functions like steroidogenesis, spermatogenesis and the onset of puberty, sexual maturity, sexual behavior and fertility. Exposure to Cd may even cause changes in the immune system that are associated with the reproductive system. This review analyses the state of the question regarding Cd's cellular and physiological mechanisms and the effects of this heavy metal on the neuroendocrine regulation of male reproduction.

Neonatal treatment with clomipramine modifies the expression of estrogen receptors in brain areas of male adult rats.

The participation of estrogens in depression has been well recognized. To exert its effects, estradiol binds mainly to estrogen receptors ESR1 and ESR2 (α and ß, respectively), expressed in brain regions including the hippocampus, limbic regions and hypothalamic nuclei. In rodents, modified estrogen receptors expression in brain areas have been implicated in different signs similar to those observed in depressive patients. Neonatal clomipramine (CMI) treatment is a pharmacological manipulation that generates behavioral and neurochemical changes that persist throughout adulthood and resemble human depression. The aim of this study was to analyze whether CMI neonatal treatment modifies the expression of nuclear ESR1 and ESR2 in the hippocampus, amygdala basolateral (BLA), amygdala medial (MeA), hypothalamic medial preoptic area (mPOA) and raphe nucleus in male rats. Our results indicate that CMI treatment significantly induced an mRNA increase of ESR1 in the hypothalamus, additionally produce a reduction in the mRNA ESR2 expression in raphe accompanied of an increase in hypothalamus and amygdala. CMI treated rats show more immunorreactive cells to ESR1 (ESR1-ir) in mPOA, BLA, MeA, together with a reduction of these cells in the hippocampal CA1 region. Moreover, an increase in the number of immunorreactive cells to ESR2 (ESR2-ir), in BLA and MeA, was observed in CMI treated rats. Additionally, the hippocampal CA2 region and raphe nucleus showed a decrease in these cells. Also, neonatal CMI treatment induced a decrease in the number of cells of the pyramidal layer in CA1. Overall, the results suggest that neonatal CMI treatment in rats (during brain development) induces changes in estrogen receptors in different brain areas involved with the regulation of depressive-like behaviors.

Paternal behavior in the Mongolian gerbil, and its regulation by social factors, T, ERα, and AR.

The present study evaluates the role of social factors in the transition from infanticidal to paternal male behavior and its association with T concentration, presence of estrogen receptor alpha (ERα) and androgen receptor (AR) in the olfactory bulb (OB), medial preoptic area (mPOA) and medial amygdala (MeA) of Mongolian gerbils (Meriones unguiculatus). This study included thirty-six sexually inexperienced males displaying aggressive behavior toward foreign pups. The selected animals were mated and organized into four groups. The paternal behavior tests were performed on the day of copulation (DCOPUL), during cohabitation with a pregnant female (CPREG), on the day of birth (DBIRTH), and on day 6 postpartum (DPP6). Eight sexually inexperienced males (CTL (male-male cohabitation) were used as control. After paternal behavior tests, blood samples were obtained to quantify T by radioimmunoassay; the brains were removed and analyzed for immunoreactivity (ir) of ERα and AR. All males of the DCOPUL, DBIRTH, and DPP6 groups exhibited paternal behavior, whereas the males of CPREG and CTL groups were aggressive with the pups. Paternal behavior was associated with high T concentrations, and the presence of ERα-ir and AR-ir in the OB, MeA, and mPOA. These results suggest that the transition from aggressive to paternal response to pups is facilitated by copulation, and that in this transition is involved an increase in T concentration. Moreover, the presence of ERα-ir and AR-ir in the OB, mPOA, and MeA could indicate that estrogenic and androgenic pathways participate in the regulation of paternal behavior of the Mongolian gerbils.

Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems.

Prolactin function and putative expression in the brain.

INTRODUCTION: Prolactin is a peptide hormone mainly synthetized and secreted by the anterior pituitary gland, but also by extrapituitary tissues, such as mammary gland, decidua, prostate, skin, and possibly the brain. Similarly, prolactin receptor is expressed in the pituitary gland, many peripheral tissues, and in contrast to prolactin, its receptor has been consistently detected in several brain regions, such as cerebral cortex, olfactory bulb, hypothalamus, hippocampus, amygdala, among others. Classically, prolactin function has been related to the stimulation of lactogenesis and galactopoiesis, however, it is well known that prolactin induces a wide range of functions in different brain areas. PURPOSE: The aim of this review is to summarize recent reports on prolactin and prolactin receptor synthesis and localization, as well as recapitulate both the classic functions attributed to this hormone in the brain and the recently described functions such as neurogenesis, neurodevelopment, sleep, learning and memory, and neuroprotection. CONCLUSION: The distribution and putative expression of prolactin and its receptors in several neuronal tissues suggests that this hormone has pleiotropic functions in the brain.

Hormone replacement with 17ß-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17ß-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17ß-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17ß-estradiol levels, and the role of testosterone, 17ß-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17ß-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17ß-estradiol +5-α-dihydrotestosterone, but not testosterone.

Altered expression of 5-HT1A receptors in adult rats induced by neonatal treatment with clomipramine.

Chronic administration of clomipramine (CMI) to neonatal rats produces behaviors that resemble a depressive state in adulthood. Dysfunctions in the activity of the central nervous system's serotonergic function are important in understanding the pathophysiology of depression. The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the long latency of some antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide. In this study, we analyzed the effect of neonatal administration of CMI on the activity of 5-HT1A receptors, both pre- and post-synaptically, by administering an agonist of 5-HT1A receptors, 8-OH-DPAT, and then subjecting the rats to the forced swimming test (FST) a common procedure used to detect signs of depression in rats. Also measured were levels of the mRNA expression of 5-HT1A receptors in the dorsal raphe (DR), the hypothalamus and the hippocampus. Wistar rats were injected twice daily with CMI at doses of 15mgkg(-1) or saline as vehicle (CON) via s.c. from postnatal day 8 for 14days. At 3-4months of age, one set of rats from each group (CON, CMI) was evaluated for the effect of a selective agonist to the 5-HT1A receptor subtype, 8-OH-DPAT, by testing in the FST. Also determined was the participation of the pre- or post-synaptic 5-HT1A receptor in the antidepressant-like action of 8-OH-DPAT. This involved administering an inhibitor of tryptophan hydroxylase, parachlorophenylalanine (PCPA), and pretreatment with 8-OH-DPAT before the FST test and to evaluate the rectal temperature and locomotor activity. The expression of the mRNA of the 5-HT1A receptors was examined in the dorsal raphe nucleus, the hypothalamus and the hippocampus using the semi-quantitative RT-PCR method. The results from this study corroborate that neonatal treatment with clomipramine induces a pronounced immobility in the FST when animals reach adulthood, manifested by a significant decrease in swimming behavior, though counts of climbing behavior were not modified. This effect was similar in magnitude when 8-OH-DPAT was administered to CON group. Furthermore, the administration of 8-OH-DPAT induces a significant and similar increase in rectal temperature and locomotor activity in both the CON as in the CMI group. Neonatal treatment with CMI resulted in a significant decrease in the expression of the mRNA of the 5-HT1A receptors in the DR (% more than vehicle) in adulthood. In the case of the postsynaptic receptors located in the hypothalamus and hippocampus, neonatal treatment with CMI induced a significant increase in the mRNA expression of the 5-HT1A receptors. These data suggest that neonatal treatment with CMI induces a downregulation of the mRNA of the 5-HT1A autoreceptors in the DR, and an increment in the expression of the postsynaptic 5-HT1A receptors. The results after the administration of PCPA and 8-OH-DPAT on FST, rectal temperature and locomotor activity for both groups suggest that the function of postsynaptic receptors remains unchanged. All together these data show that the depressive behavior observed in adulthood in this animal model may be associated with long-term alterations in the expression of the mRNA of the 5-HT1A receptors.