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Frontiers in Endocrinology 2020Neural circuits in female rats sequentially exposed to estradiol and progesterone underlie so-called estrogen positive feedback that induce the surge release of... (Review)
Review
Neural circuits in female rats sequentially exposed to estradiol and progesterone underlie so-called estrogen positive feedback that induce the surge release of pituitary luteinizing hormone (LH) leading to ovulation and luteinization of the corpus hemorrhagicum. It is now well-established that gonadotropin releasing hormone (GnRH) neurons express neither the reproductively critical estrogen receptor-α (ERα) nor classical progesterone receptor (PGR). Estradiol from developing ovarian follicles acts on ERα-expressing kisspeptin neurons in the rostral periventricular region of the third ventricle (RP3V) to induce PGR expression, and kisspeptin release. Circulating estradiol levels that induce positive feedback also induce neuroprogesterone (neuroP) synthesis in hypothalamic astrocytes. This local neuroP acts on kisspeptin neurons that express PGR to augment kisspeptin expression and release needed to stimulate GnRH release, triggering the LH surge. and studies demonstrate that neuroP signaling in kisspeptin neurons occurs through membrane PGR activation of Src family kinase (Src). This signaling cascade has been also implicated in PGR signaling in the arcuate nucleus of the hypothalamus, suggesting that Src may be a common mode of membrane PGR signaling. Sexual maturation requires that signaling between neuroP synthesizing astrocytes, kisspeptin and GnRH neurons be established. Prior to puberty, estradiol does not facilitate the synthesis of neuroP in hypothalamic astrocytes. During pubertal development, levels of membrane ERα increase in astrocytes coincident with an increase of PKA phosphorylation needed for neuroP synthesis. Currently, it is not clear whether these developmental changes occur in existing astrocytes or are due to a new population of astrocytes born during puberty. However, strong evidence suggests that it is the former. Blocking new cell addition during puberty attenuates the LH surge. Together these results demonstrate the importance of pubertal maturation involving hypothalamic astrocytes, estradiol-induced neuroP synthesis and membrane-initiated progesterone signaling for the CNS control of ovulation and reproduction.
Topics: Animals; Astrocytes; Humans; Hypothalamus; Luteinizing Hormone; Neurons; Ovulation; Progesterone; Reproduction; Sexual Maturation
PubMed: 32670203
DOI: 10.3389/fendo.2020.00420 -
Journal of Assisted Reproduction and... Oct 2018
Topics: Corpus Luteum; Female; Humans; Luteinization; Ovulation; Progesterone
PubMed: 30218419
DOI: 10.1007/s10815-018-1312-4 -
Fertility and Sterility Apr 2019The advent of third party parenting ushered in the era of artificial stimulation of the endometrium. Initially intended only for patients with ovarian failure, exogenous... (Review)
Review
The advent of third party parenting ushered in the era of artificial stimulation of the endometrium. Initially intended only for patients with ovarian failure, exogenous induction of endometrial receptivity was quickly shown to be as good as natural endometrial preparation, with the advantage that the timing of embryo transfer could be controlled. It is perhaps surprising that even though the ovary produces a variety of steroids, that estradiol (E) and progesterone (P) alone would be needed to achieve optimal receptivity; no other substance has ever been shown to improve on the basic regimen of E and P. A variety of routes of administration are available for both E and P and physiologic (or supraphysiologic) serum or endometrial tissue levels of both can be achieved. The optimal duration of E stimulation and the timing of the onset of P administration continue to be debated, but it appears that imitating the sequence that normally occurs in nature leads to optimal results. The poorly responsive endometrium and cases of recurrent implantation failure remain a challenge, but the clear majority of patients can successfully achieve pregnancy as long as embryos of adequate quality are transferred.
Topics: Cryopreservation; Embryo Implantation; Embryo Transfer; Endometrium; Estradiol; Female; Fertility Agents, Female; Humans; Luteinization; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted; Surrogate Mothers
PubMed: 30929721
DOI: 10.1016/j.fertnstert.2019.02.010 -
Andrologia Feb 2021To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July...
To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID-19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID-19 and those who were not. Any differences between those who had COVID-19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID-19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID-19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID-19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID-19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID-19 infection, especially in the patient group with viral pneumonia.
Topics: Adult; COVID-19; COVID-19 Testing; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Polymerase Chain Reaction; Prospective Studies; SARS-CoV-2; Testosterone; Tomography, X-Ray Computed
PubMed: 33210743
DOI: 10.1111/and.13909 -
Handbook of Experimental Pharmacology 2010Infertility adversely affects many couples worldwide. Conversely, the exponential increase in world population threatens our planet and its resources. Therefore, a... (Review)
Review
Infertility adversely affects many couples worldwide. Conversely, the exponential increase in world population threatens our planet and its resources. Therefore, a greater understanding of the fundamental cellular and molecular events that control the size of the primordial follicle pool and follicular development is of utmost importance to develop improved in vitro fertilization as well as to design novel approaches to regulate fertility. In this review we attempt to highlight some new advances in basic research of the mammalian ovary that have occurred in recent years focusing primarily on mouse models that have contributed to our understanding of ovarian follicle formation, development, and ovulation. We hope that these new insights into ovarian function will trigger more research and translation to clinically relevant problems.
Topics: Animals; Cell Differentiation; Female; Granulosa Cells; Humans; Luteinization; Meiosis; Ovarian Follicle; Ovary; Transcription Factors; Transforming Growth Factor beta
PubMed: 20839083
DOI: 10.1007/978-3-642-02062-9_1 -
Frontiers in Endocrinology 2020
Topics: Animals; Cell Differentiation; Corpus Luteum; Corpus Luteum Maintenance; Female; Humans; Pregnancy
PubMed: 32390947
DOI: 10.3389/fendo.2020.00244 -
Reproductive Biology Dec 2013The primate corpus luteum is a transient endocrine gland that differentiates from the ovulatory follicle midway through the ovarian (menstrual) cycle. Its formation and... (Review)
Review
The primate corpus luteum is a transient endocrine gland that differentiates from the ovulatory follicle midway through the ovarian (menstrual) cycle. Its formation and limited lifespan is critical for fertility, as luteal-derived progesterone is the essential steroid hormone required for embryo implantation and maintenance of intra-uterine pregnancy until the placenta develops. It is well-established that LH and the LH-like hormone, CG, are the vital luteotropic hormones during the menstrual cycle and early pregnancy, respectively. Recent advances, particularly through genome analyses and cellular studies, increased our understanding of various local factors and cellular processes associated with the development, maintenance and repression of the corpus luteum. These include paracrine or autocrine factors associated with angiogenesis (e.g., VEGF), and that mediate LH/CG actions (e.g., progesterone), or counteract luteotropic effects (i.e., local luteolysis; e.g., PGF2α). However, areas of mystery and controversy remain, particularly regarding the signals and events that initiate luteal regression in the non-fecund cycle. Novel approaches capable of gene "knockdown" or amplification", in vivo as well as in vitro, should identify novel or underappreciated gene products that are regulated by or modulate LH/CG actions to control the functional lifespan of the primate corpus luteum. Further advances in our understanding of luteal physiology will help to improve or control fertility for purposes ranging from preservation of endangered primate species to designing novel ovary-based contraceptives and treating ovarian disorders in women.
Topics: Animals; Chorionic Gonadotropin; Corpus Luteum; Female; Fertility; Humans; Kisspeptins; Luteinizing Hormone; Luteolysis; Neovascularization, Physiologic; Pregnancy; Primates; Progesterone
PubMed: 24287034
DOI: 10.1016/j.repbio.2013.08.002 -
Endocrinology Feb 2018Placental growth factor (PGF) is member of the vascular endothelial growth factor (VEGF) family of angiogenesis regulators. VEGFA is an established regulator of...
Placental growth factor (PGF) is member of the vascular endothelial growth factor (VEGF) family of angiogenesis regulators. VEGFA is an established regulator of ovulation and formation of the corpus luteum. To determine whether PGF also mediates aspects of ovulation and luteinization, macaques received gonadotropins to stimulate multiple follicular development. Ovarian biopsies and whole ovaries were collected before (0 hours) and up to 36 hours after human chorionic gonadotropin (hCG) administration to span the ovulatory interval. PGF and VEGFA were expressed by both granulosa cells and theca cells. In follicular fluid, PGF and VEGFA levels were lowest before hCG. PGF levels remained low until 36 hours after hCG administration, when PGF increased sevenfold to reach peak levels. Follicular fluid VEGFA increased threefold to reach peak levels at 12 hours after hCG, then dropped to intermediate levels. To explore the roles of PGF and VEGFA in ovulation, luteinization, and follicular angiogenesis in vivo, antibodies were injected into the follicular fluid of naturally developed monkey follicles; ovariectomy was performed 48 hours after hCG, with ovulation expected about 40 hours after hCG. Intrafollicular injection of control immunoglobulin G resulted in no retained oocytes, follicle rupture, and structural luteinization, including granulosa cell hypertrophy and capillary formation in the granulosa cell layer. PGF antibody injection resulted in oocyte retention, abnormal rupture, and incomplete luteinization, with limited and disorganized angiogenesis. Injection of a VEGFA antibody resulted in oocyte retention and very limited follicle rupture or structural luteinization. These studies demonstrate that PGF, in addition to VEGFA, is required for ovulation, luteinization, and follicular angiogenesis in primates.
Topics: Angiogenesis Inducing Agents; Animals; Female; Luteinization; Luteinizing Hormone; Macaca fascicularis; Neovascularization, Physiologic; Ovarian Follicle; Ovulation; Placenta Growth Factor; Vascular Endothelial Growth Factor A
PubMed: 29095972
DOI: 10.1210/en.2017-00739 -
Fertility and Sterility Sep 2009To summarize recent advances in the understanding of the endocrine signaling pathways between the hypothalamus, pituitary, and human corpus luteum (CL); to examine the... (Review)
Review
OBJECTIVE
To summarize recent advances in the understanding of the endocrine signaling pathways between the hypothalamus, pituitary, and human corpus luteum (CL); to examine the major paracrine and autocrine mechanisms and the key genes and proteins involved in CL development, function, and regression in natural cycles; to review the endocrine and molecular response of the midluteal phase CL to in vivo administration of human chorionic gonadotropin (hCG); and to describe the ultrasonographic and Doppler evaluation of the ovary and endometrium throughout the luteal phase.
DESIGN
Published data in the literature, including the basic and clinical research studies of the authors.
SETTING
University-affiliated hospital and research centers.
PATIENT(S)
None.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Clinical and molecular analysis of human CL function.
RESULT(S)
The endocrine function of the subpopulations of luteal cells is critical for the maintenance of CL function, including neovacularization and steroid hormones production. We consider the key genes and proteins that favor development of luteal structure and function throughout the menstrual cycle and in our model of hCG treatment resembling early pregnancy.
CONCLUSION(S)
These data indicate that the functional lifespan of the CL depends on paracrine and autocrine mechanisms. Therefore, the significance of the key genes and proteins that we analyze in lutein cells during CL development, function, demise, and rescue by hCG is likely to bring new therapeutic applications for the management of fertility defects and the control of fertility.
Topics: Corpus Luteum; Female; Fertility; Humans; Luteal Phase; Luteinization; Luteolysis; Menstrual Cycle; Ovary; Ultrasonography
PubMed: 18793774
DOI: 10.1016/j.fertnstert.2008.07.1745 -
Frontiers in Endocrinology 2022Infertility is a major global health issue and is associated with significant psychological distress for afflicted couples. fertilisation (IVF) utilises... (Review)
Review
Infertility is a major global health issue and is associated with significant psychological distress for afflicted couples. fertilisation (IVF) utilises supra-physiological doses of stimulatory hormones to induce the growth of multiple ovarian follicles to enable surgical retrieval of several oocytes for subsequent fertilisation and implantation into the maternal endometrium. The supra-physiological degree of ovarian stimulation can lead to potential risks during IVF treatment, including ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The choice of oocyte maturation trigger, such as human chorionic gonadotrophin (hCG) or gonadotrophin releasing hormone agonist (GnRHa), can impact both the efficacy of IVF treatment with a bearing on luteal phase hormonal dynamics and thus the degree of luteal phase support required to maintain optimal pregnancy rates, as well as on safety of treatment with particular respect to the risk of OHSS. Kisspeptin regulates gonadotrophin releasing hormone (GnRH) release and is therefore a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. Kisspeptin has been shown to be requisite for the occurrence of the physiological ovulatory luteinising hormone (LH) surge. In this review, we discuss the potential use of kisspeptin as a novel trigger of oocyte maturation.
Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Luteinizing Hormone; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy
PubMed: 36147569
DOI: 10.3389/fendo.2022.972137