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Reproduction in Domestic Animals =... Sep 2023Stress is defined as a disruption of the body homeostasis in response to modest as well as perceived challenge. Two main physiological routes, the... (Review)
Review
Pathogenesis of the crosstalk between reproductive function and stress in animals-part 1: Hypothalamo-pituitary-adrenal axis, sympatho-adrenomedullary system and kisspeptin.
Stress is defined as a disruption of the body homeostasis in response to modest as well as perceived challenge. Two main physiological routes, the hypothalamic-pituitary-adrenal system (HPA) and the sympatho-adrenomedullary system (SAM), aim to maintain or restore homeostasis by mutual interaction. SAM is quickly-reacting as it primarily works through the nervous system-the sympathetic nervous system. In response to stress, signals are sent to activate the adrenal medulla which releases catecholamines (primarily adrenaline and norepinephrine). The catecholamines have a momentary effect on the body's organs that are prepared for a fight situation. At the same time, the stressor activates the HPA axis by signals from the brain causing secretion of the pituitary hormone adrenocorticotropic hormone (ACTH). ACTH acts on the adrenal cortex, which secretes glucocorticoids, including cortisol. Since HPA primarily works through hormones, the system is slightly slower than SAM and gives rise to a metabolic effect. While short-term stress response is an adaptive and beneficial process, chronic or excessive stress can lead to a range of negative health outcomes including reproductive disorders and infertility. Several mechanisms have been proposed to explain the link between stress and reproduction. This includes in particular kisspeptin, which is closely related to reproduction, as it is a powerful stimulator of the Hypothalamic-pituitary-gonadal (HPG) system. The present review, through current knowledge in various male and female species, deals with the role of the SAM and the HPA, including the major action of kisspeptin and glucocorticoids that trigger the consequences of psychological or physiological stress on reproductive function.
Topics: Female; Male; Animals; Hypothalamo-Hypophyseal System; Kisspeptins; Glucocorticoids; Pituitary-Adrenal System; Adrenocorticotropic Hormone; Catecholamines
PubMed: 37724657
DOI: 10.1111/rda.14444 -
The Journal of International Medical... Sep 2023To identify the effects of metformin and kisspeptin structural polymorphism on the risk of polycystic ovary syndrome (PCOS) in Iraqi women.
OBJECTIVE
To identify the effects of metformin and kisspeptin structural polymorphism on the risk of polycystic ovary syndrome (PCOS) in Iraqi women.
METHODS
Samples were collected at the family planning center of Al-Hassan Teaching Hospital (infertility clinic), Iraq. Hormonal and hematological parameters were measured. Kisspeptin structural polymorphisms were analyzed by polymerase chain reaction using a conventional thermal cycler and Phyre2 predictions. Kisspeptin concentrations were assessed by an enzyme-linked immunosorbent assay.
RESULTS
Follicle-stimulating hormone (FSH) was the only sex hormone that changed in women with PCOS after metformin treatment. FSH concentrations were significantly increased after therapy compared with before therapy (9.39 ± 2.1 vs 5.13 ± 1.53 IU/L). We found that a single nucleotide polymorphism substituting G to C was related to PCOS. The kisspeptin structural polymorphism showed that the C allele was related to low FSH concentrations after treatment (6.92 ± 2.2 IU/L to 5.34 ± 1.58 IU/L). Kisspeptin concentrations were significantly lower after metformin treatment than before metformin treatment (395.44 ± 67.83 vs 273.18 ± 42.98 ng/mL).
CONCLUSION
A variation in the gene or its protein structure may be involved in the development of PCOS. The response to metformin may be used as an indicator and could contribute to the early diagnosis and medical therapy of PCOS.
Topics: Humans; Female; Kisspeptins; Iraq; Polycystic Ovary Syndrome; Follicle Stimulating Hormone, Human; Polymorphism, Single Nucleotide; Metformin
PubMed: 37702549
DOI: 10.1177/03000605231196837 -
Biology of Reproduction Nov 2023Kisspeptin (KP, encoded by Kiss1, binding to the Gpr54 receptor) is a neuropeptide conveying information on the metabolic status to the hypothalamic-pituitary-gonadal...
Maternal cafeteria diet influences kisspeptin (Kiss1), kisspeptin receptor(Gpr54), and sirtuin (Sirt1) genes, hormonal and metabolic profiles, and reproductive functions in rat offspring in a sex-specific manner†.
Kisspeptin (KP, encoded by Kiss1, binding to the Gpr54 receptor) is a neuropeptide conveying information on the metabolic status to the hypothalamic-pituitary-gonadal axis. KP acts together with dynorphin A (encoded by Pdyn) and neurokinin B (encoded by Tac2) to regulate reproduction. KP is crucial for the onset of puberty and is under the control of sirtuin (encoded by Sirt1). We hypothesize that the maternal cafeteria (CAF) diet has adverse effects on the offspring's hormonal, metabolic, and reproductive functions due to sex-specific alterations in the expression of Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 in the hypothalamus, and Kiss1, Gpr54, and Sirt1 in the liver. Rats were fed a CAF diet before pregnancy, during pregnancy, and during lactation. The vaginal opening was monitored. Offspring were sacrificed in three age points: PND 30, PND 35, and PND 60 (females) and PND 40, PND 45, and PND 60 (males). Their metabolic and hormonal status was assessed. mRNA for Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 were measured by real-time PCR in the hypothalamus and/or livers. We found that CAF offspring had lower weight and altered body composition; increased cholesterol and triglyceride levels, sex-specific changes in glucose and insulin levels; sex-dependent changes in Sirt1/Kiss1 mRNA ratio in the hypothalamus; sex-specific alterations in Kiss1 and Sirt1 mRNA in the liver with more diversity in males; and a delayed puberty onset in females. We concluded that the mother's CAF diet leads to sex-specific alterations in metabolic and reproductive outcomes via Kiss1/Gpr54 and Sirt1 systems in offspring.
Topics: Pregnancy; Female; Male; Rats; Animals; Kisspeptins; Sirtuin 1; Sexual Maturation; Receptors, Kisspeptin-1; Diet; Metabolome; RNA, Messenger
PubMed: 37665248
DOI: 10.1093/biolre/ioad101 -
Zygote (Cambridge, England) Dec 2023Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this...
Kisspeptin is characterized as a neuropeptide with a pivotal function in female and male infertility, and its antioxidant properties have been demonstrated. In this study, the effects of kisspeptin on the improvement of the vitrification and thawing results of human ovarian tissues were investigated. In this work, 12 ovaries from patients who underwent hysterectomy were collected laparoscopically, and then 32 samples from each of their tissues were taken. Haematoxylin and eosin (H&E) staining was performed to check the normality of the ovarian tissue and, subsequently, the samples were allocated randomly into four groups, including: (1) fresh (control), (2) vitrification, (3) vitrified + 1 μM kisspeptin, and (4) vitrified + 10 μM kisspeptin groups. After vitrification, thawing, and tissue culture processes, H&E staining for tissue quality assessment, terminal deoxynucleotidyl transferase dUTP nick end labelling assay for apoptosis evaluation, and malondialdehyde (MDA), superoxide dismutase (SOD), and ferric reducing ability of plasma tests for oxidative stress appraisal were carried out. Our histological results showed incoherency of ovarian tissue morphology in the vitrification group compared with other groups. Other findings implicated increased apoptosis rate and MDA concentration and reduced SOD activity and total antioxidant capacity (TAC) in the vitrification group compared with the control group ( < 0.05). Moreover, decreased apoptosis rate and MDA concentration, and increased TAC and SOD function were observed in the vitrification with kisspeptin groups (1 μM and 10 μM) compared with the vitrified group ( < 0.05). Our reports express that kisspeptin is an effective agent to overcome the negative effects of vitrification by regulating reactive oxygen species-related apoptotic processes.
Topics: Humans; Male; Female; Vitrification; Ovary; Cryopreservation; Kisspeptins; Reactive Oxygen Species; Antioxidants; Superoxide Dismutase
PubMed: 37655529
DOI: 10.1017/S0967199423000412 -
In Vivo (Athens, Greece) 2023To investigate the possible association of kisspeptin levels with the ovarian reserves of women of reproductive age.
BACKGROUND/AIM
To investigate the possible association of kisspeptin levels with the ovarian reserves of women of reproductive age.
PATIENTS AND METHODS
Eighty women aged 19-40 participated after signing an informed consent. Of these, 74 were finally included as in 6 women the blood samples were considered inappropriate due to hemolysis. They were divided into three main groups according to their ovarian reserve patterns: women with adequate ovarian reserves (Group A - AOR) (n=30), women with increased ovarian reserves (Group B - PCOS) (n=31), and women with diminished ovarian reserves (Group C - DOR) (n=13).
RESULTS
Women with diminished ovarian reserves had statistically significantly increased age and FSH compared to the other two groups. No statistically significant difference was found between the three groups for estradiol and thyroid stimulating hormone. Moreover, body mass index, luteinizing hormone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone, anti-Mullerian hormone (AMH), and antral follicle count (AFC) were increased in group B compared to the other two groups. AMH and AFC were decreased in women with diminished ovarian reserves compared to the other two groups, as expected. The comparison of kisspeptin levels between the three groups showed that kisspeptin levels were increased in women with diminished ovarian reserves, compared to the other two groups, but without a statistically significant difference. However, kisspeptin levels in group C were statistically significantly higher than those in group A.
CONCLUSION
There are no strong indications that kisspeptin levels are associated with the ovarian reserve in women of reproductive age.
Topics: Female; Humans; Ovarian Reserve; Kisspeptins; Testosterone; Anti-Mullerian Hormone; Estradiol
PubMed: 37652519
DOI: 10.21873/invivo.13322 -
Zhen Ci Yan Jiu = Acupuncture Research Aug 2023To observe the effects of electroacupuncture (EA) on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of...
OBJECTIVE
To observe the effects of electroacupuncture (EA) on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome (PCOS), so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats.
METHODS
Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole (0.1 mg/mL, 10 mL•kg•d). In the EA group, EA (2 Hz, 2 mA) was used to stimulate "Guanyuan" (CV4) for 20 min each time. In the flutamide group, flutamide solution (50 mg•kg•d) was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone (T), luteinizing hormone (LH) and estradiol (E) in serum, the contents of E and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot.
RESULTS
Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased (<0.01, <0.05); and the content of E in the culture medium of granulosa cells was decreased (<0.01) in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased (<0.01, <0.05); and the content of E in the culture medium of granulosa cells was increased (<0.05, <0.01).
CONCLUSION
EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.
Topics: Animals; Female; Humans; Rats; Electroacupuncture; Flutamide; Kisspeptins; Luteinizing Hormone; Polycystic Ovary Syndrome
PubMed: 37614139
DOI: 10.13702/j.1000⁃0607.20220481 -
International Journal of Molecular... Jul 2023We demonstrate here that highly sensitive in vitro bioassays for FSH, TSH, and PTH can be set up in mouse Leydig Tumor Cells (mLTC), in addition to the normal LH/CG...
We demonstrate here that highly sensitive in vitro bioassays for FSH, TSH, and PTH can be set up in mouse Leydig Tumor Cells (mLTC), in addition to the normal LH/CG bioassay, after they were transfected with expression vectors encoding the corresponding Gs Protein-Coupled Receptors (GsPCR), such as FSHR, TSHR, or PTHR. Although the β2 adrenergic receptor is also a GsPCR, its expression in mLTC led to a significant but very low cAMP response compared to those observed with FSH, TSH, or PTH. Similarly, after transfection of the GiPCR MT1 melatonin receptor, we did not observe any inhibitory effect by melatonin of the LH or hCG stimulation. Interestingly, after transfection of mLTC with the human kisspeptin receptor (hKpR), which is a GqPCR, we observed a dose-dependent synergy of 10-10 M kisspeptin variants with a fixed concentration of 0.3 nM LH or hCG. Without any exogenous receptor transfection, a 2 h preincubation with OT or AVP led to a dose-dependent cAMP response to a fixed dose of LH or hCG. Therefore, highly sensitive in vitro bioassays for various hormones and other GPCR ligands can be set up in mLTC to measure circulating concentrations in only 3-10 µL of blood or other body fluids. Nevertheless, the development of an LHRKO mLTC cell line will be mandatory to obtain strict specificity for these bioassays to eliminate potential cross-reaction with LH or CG.
Topics: Mice; Animals; Humans; Receptors, LH; Kisspeptins; Ligands; Cyclic AMP; Signal Transduction; Receptors, G-Protein-Coupled; Follicle Stimulating Hormone; Thyrotropin; Chorionic Gonadotropin
PubMed: 37569429
DOI: 10.3390/ijms241512047 -
The Journal of Endocrinology Sep 2023Reproduction in mammals is an extremely energy-intensive process and is therefore tightly controlled by the body's energy status. Changes in the nutritional status of... (Review)
Review
Reproduction in mammals is an extremely energy-intensive process and is therefore tightly controlled by the body's energy status. Changes in the nutritional status of the body cause fluctuations in the levels of peripheral metabolic hormone signals, such as leptin, insulin, and ghrelin, which provide feedback to the hypothalamus and integrate to coordinate metabolism and fertility. Therefore, to link energy and reproduction, energetic information must be centrally transmitted to gonadotropin-releasing hormone (GnRH) neurons that act as reproductive gating. However, GnRH neurons themselves are rarely directly involved in energy information perception. First, as key factors in the control of GnRH neurons, we describe the direct role of Kisspeptin and Arg-Phe amide-related peptide-3 (RFRP-3) neurons in mediating metabolic signaling. Second, we focused on summarizing the roles of metabolic hormone-sensitive neurons in mediating peripheral energy hormone signaling. Some of these hormone-sensitive neurons can directly transmit energy information to GnRH neurons, such as Orexin neurons, while others act indirectly through other neurons such as Kisspeptin, RFRP-3 neuron, and (pituitary adenylate cyclase-activating polypeptide) PACAP neurons. In addition, as another important aspect of the integration of metabolism and reproduction, the impact of reproductive signaling itself on metabolic function was also considered, as exemplified by our examination of the role of Kisspeptin and RFRP-3 in feeding control. This review summarizes the latest research progress in related fields, in order to more fully understand the central neuropeptide network that integrates energy metabolism and reproduction.
Topics: Animals; Kisspeptins; Reproduction; Gonadotropin-Releasing Hormone; Hypothalamus; Mammals
PubMed: 37561042
DOI: 10.1530/JOE-23-0079 -
Reproductive Medicine (Basel,... Dec 2022Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE...
Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated. Herein, we used the preeclamptic-like BPH/5 mouse model to investigate kisspeptin expression and potential upstream regulatory mechanisms in a PE-like syndrome. Expression of the kisspeptin encoding gene, , and the 10-amino-acid kisspeptide (Kp-10), are upregulated in the non-pregnant uterus of BPH/5 females during diestrus and in the maternal-fetal interface during embryonic implantation and decidualization. Correspondingly, the dysregulation of molecular pathways downstream to kisspeptins also occurs in this mouse model. BPH/5 females have abnormal sex steroid hormone profiles during early gestation. In this study, the normalization of circulating concentrations of 17β-estradiol (E2) and progesterone (P4) in pregnant BPH/5 females not only mitigated upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine upregulation occurs pre-pregnancy and persists during early gestation in a PE-like mouse model. Moreover, this study highlights the role of sex steroid hormones in uteroplacental dysregulation and the improvement of placentation by normalization of E2, P4 and .
PubMed: 37538930
DOI: 10.3390/reprodmed3040021 -
Frontiers in Endocrinology 2023
Topics: Humans; Kisspeptins; Reproduction; Luteinizing Hormone; Neoplasms
PubMed: 37522118
DOI: 10.3389/fendo.2023.1239694