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Reproduction (Cambridge, England) May 2021Maternal recognition of pregnancy (MRP) is a process by which an early conceptus signals its presence to the maternal system and prevents the lysis of the corpus luteum,... (Review)
Review
Maternal recognition of pregnancy (MRP) is a process by which an early conceptus signals its presence to the maternal system and prevents the lysis of the corpus luteum, thus ensuring a maternal milieu supportive of pregnancy continuation. It is a fundamental aspect of reproductive biology, yet in the horse, the mechanism underlying MRP remains unknown. This review seeks to address some of the controversies surrounding the evidence and theories of MRP in the equine species, such as the idea that the horse does not conform to the MRP paradigm established in other species or that equine MRP involves a mechanical, rather than chemical, signal. The review examines the challenges of studying this particularly clandestine phenomenon along with the new tools in scientific research that will drive this quest forward in coming years, and discuss the value of knowledge gleaned along this path in the context of clinical applications for improving breeding outcomes in the horse industry.
Topics: Animals; Corpus Luteum Maintenance; Embryonic Development; Female; Horses; Pregnancy; Pregnancy, Animal
PubMed: 33957605
DOI: 10.1530/REP-20-0437 -
Scientific Reports Jun 2018Reelin plays an important role in cerebral cortex development and synaptogenesis. In the hippocampus, the neurosteroid estrogen affects reelin expression. In this study...
Reelin plays an important role in cerebral cortex development and synaptogenesis. In the hippocampus, the neurosteroid estrogen affects reelin expression. In this study we tested a potential crosstalk between estradiol and reelin, thus the possibility of a reelin-induced activation of the estradiol synthesizing enzyme aromatase. As a model system, we used ovaries, which express reelin and are a major source of estradiol. We found that in wild-type mice, reelin and aromatase are expressed in granulosa cells of growing follicles. The expression of reelin varies with the estrus cycle and is highest shortly before ovulation, when estradiol serum levels are at their maximum. In ovaries of reelin-deficient reeler mice, aromatase mRNA and protein are significantly reduced, as evidenced by real-time PCR, western blot analysis, and quantitative immunohistochemistry in granulosa cells of preovulatory follicles. In line with reduced estradiol synthesis, ovarian estrus cycle length is prolonged in reeler mice. Most importantly, treating cultured granulosa cells with recombinant reelin results in significant upregulation of aromatase mRNA and protein and increased secretion of estradiol into the supernatant. Our data provide evidence of a local increase of aromatase expression by reelin. Regarding reproduction, this crosstalk may contribute to follicular stability and counteract luteinization in ovaries.
Topics: Animals; Aromatase; Cell Adhesion Molecules, Neuronal; Estrous Cycle; Extracellular Matrix Proteins; Female; Gene Expression Regulation, Enzymologic; Granulosa Cells; Luteinization; Mice; Nerve Tissue Proteins; Rats, Wistar; Reelin Protein; Serine Endopeptidases
PubMed: 29880879
DOI: 10.1038/s41598-018-26928-x -
Journal of Medicine and Life Sep 2022The present experimental model aimed to investigate the possible effect of endometriosis on ovarian function by altering follicular maturation and development. This...
The present experimental model aimed to investigate the possible effect of endometriosis on ovarian function by altering follicular maturation and development. This single-blind, randomized study included twenty-four female Sprague Dawley mice, 2.5 months old, weighing 160-200 grams. The animals were randomly separated into four groups on the day of the surgery. Each group consisted of 6 mice. The first group (A) consisted of healthy female mice (control group). The second group (B) consisted of mice subjected to surgical insertion of ovarian endometrioma. The third group (C) consisted of mice subjected to surgically induced diffuse intraperitoneal endometriosis, and the fourth group (D) consisted of mice subjected to surgically induced extraperitoneal endometriosis. According to our experimental model, endometriosis may affect ovarian function by increasing the number of luteinized unruptured follicles (follicles that have undergone luteinization without prior rupture).
Topics: Humans; Female; Mice; Animals; Endometriosis; Single-Blind Method; Infertility, Female; Fertility; Models, Animal
PubMed: 36415526
DOI: 10.25122/jml-2021-0391 -
Reproduction, Nutrition, Development 1999Many mammalian species from temperate latitudes exhibit seasonal variations in breeding activity which are controlled by the annual photoperiodic cycle. Photoperiodic... (Review)
Review
Many mammalian species from temperate latitudes exhibit seasonal variations in breeding activity which are controlled by the annual photoperiodic cycle. Photoperiodic information is conveyed through several neural relays from the retina to the pineal gland where the light signal is translated into a daily cycle of melatonin secretion: high at night, low in the day. The length of the nocturnal secretion of melatonin reflects the duration of the night and it regulates the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Changes in GnRH release induce corresponding changes in luteinising hormone secretion which are responsible for the alternating presence or absence of ovulation in the female, and varying sperm production in the male. It is not yet known where and how this pineal indoleamine acts to exert this effect. Although melatonin binding sites are preferentially localised in the pars tuberalis (PT) of the adenohypophysis, the hypothalamus contains the physiological target sites of melatonin for its action on reproduction. Melatonin does not seem to act directly on GnRH neurons; rather it appears to involve a complex neural circuit of interneurons that includes at least dopaminergic, serotoninergic and excitatory aminoacidergic neurons.
Topics: Animals; Cricetinae; Estrus; Female; Gonadotropin-Releasing Hormone; Gonads; Hypothalamo-Hypophyseal System; Interneurons; Luteinizing Hormone; Male; Melatonin; Neurotransmitter Agents; Photoperiod; Pineal Gland; Pituitary Gland, Anterior; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Melatonin; Reproduction; Rodentia; Seasons; Secretory Rate; Sheep; Species Specificity
PubMed: 10420438
DOI: 10.1051/rnd:19990308 -
General and Comparative Endocrinology Dec 2022Understanding the hypothalamic factors regulating reproduction facilitates maximising the reproductive success of breeding programmes and in the management and...
Provocative tests with Kisspeptin-10 and GnRH set the scene for determining social status and environmental impacts on reproductive capacity in male African lions (Panthera leo).
Understanding the hypothalamic factors regulating reproduction facilitates maximising the reproductive success of breeding programmes and in the management and conservation of threatened species, including African lions. To provide insight into the physiology and pathophysiology of the hypothalamic-pituitary-gonadal reproductive axis in lions, we studied the luteinising hormone (LH) and steroid hormone responses to gonadotropin-releasing hormone (GnRH) and its upstream regulator, kisspeptin. Six young (13.3 ± 1.7 months, 56.2 ± 4.3 kg) and four adult (40.2 ± 1.4 months, 174 ± 6 kg) male lions (Ukutula Conservation Centre, South Africa) were used in this study. Lions were immobilised with a combination of medetomidine and ketamine and an intravenous catheter was placed in a jugular, cephalic or medial saphenous vein for blood sampling at 10-min intervals for 220 min. The ten-amino acid kisspeptin which has full intrinsic activity (KP-10, 1 µg/kg) and GnRH (1 µg/kg) were administered intravenously to study their effects on LH and steroid hormone plasma concentrations, measured subsequently by ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Basal LH levels were similarly low between the age groups, but testosterone and its precursor levels were higher in the adult animals. Adult lions showed a significant LH response to KP-10 (10-fold) and GnRH (11-fold) administration (p < 0.05 and P < 0.001, respectively) whereas in young lions LH increased significantly only in response to GnRH. In adults alone, testosterone and its precursors steadily increased in response to KP-10, with no significant further increase in response to GnRH. Plasma levels of glucocorticoids in response to KP-10 remained unchanged. We suggest that provocative testing of LH and steroid stimulation with kisspeptin provides a new and sensitive tool for determining reproductive status and possibly an index of exposure to stress, environmental insults such as disease, endocrine disruptors and nutritional status. 272 words.
Topics: Animals; Male; Kisspeptins; Gonadotropin-Releasing Hormone; Lions; Chromatography, Liquid; Social Status; Tandem Mass Spectrometry; Luteinizing Hormone; Reproduction; Testosterone; Environment
PubMed: 36150474
DOI: 10.1016/j.ygcen.2022.114127 -
Fertility and Sterility Feb 1983A rational systematic evaluation is essential to the management of a couple with repeated early pregnancy wastage. Psychologic support in the form of frequent... (Review)
Review
A rational systematic evaluation is essential to the management of a couple with repeated early pregnancy wastage. Psychologic support in the form of frequent discussions and sympathetic counseling are crucial to the successful evaluation and treatment of the anxious couple. A prompt and orderly evaluation will relieve anxiety. When no etiologic factor is identified, a 60% to 80% fetal salvage rate may be expected. Once a patient conceives, serial ultrasonography, beta-hCG determination, and estradiol determination may be useful in detecting the stage of the embryonic death if subsequent abortion occurs. A karyotypic analysis of the products of conception should be performed if fetal loss occurs.
Topics: Abortion, Habitual; Blood Group Incompatibility; Chaperonin 10; Chromosome Aberrations; Chromosome Disorders; Corpus Luteum Maintenance; Diethylstilbestrol; Female; Heart Defects, Congenital; Humans; Immunosuppressive Agents; Kidney Diseases; Leiomyoma; Lupus Erythematosus, Systemic; Major Histocompatibility Complex; Peptides; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Proteins; Pregnancy in Diabetics; Prenatal Exposure Delayed Effects; Suppressor Factors, Immunologic; Thyroid Diseases; Uterine Neoplasms; Uterus
PubMed: 6337066
DOI: 10.1016/s0015-0282(16)46809-3 -
Thrombospondin 1 (THBS1) Promotes Follicular Angiogenesis, Luteinization, and Ovulation in Primates.Frontiers in Endocrinology 2019Angiogenesis is essential to both ovulation and the formation of the corpus luteum. The thrombospondin (THBS) family of glycoproteins plays diverse roles in regulation...
Angiogenesis is essential to both ovulation and the formation of the corpus luteum. The thrombospondin (THBS) family of glycoproteins plays diverse roles in regulation of angiogenesis, but the role of these vascular regulators in ovulation and luteinization remain to be elucidated. Using the cynomolgus macaque as a model for human ovulation, we demonstrated that levels of THBS1 mRNA and protein in preovulatory follicle granulosa cells increased after the ovulatory gonadotropin surge, with peak levels just before the expected time of ovulation. THBS1 treatment of monkey ovarian microvascular endothelial cells stimulated migration, proliferation, and capillary sprout formation, consistent with a pro-angiogenic action of THBS1. Injection of an anti-THBS1 antibody into monkey preovulatory follicles reduced rates of follicle rupture and oocyte release in response to an ovulatory gonadotropin stimulus when compared with control IgG-injected follicles. Interestingly, two of three oocytes from anti-THBS1 antibody injected follicles were germinal vesicle intact, indicating that meiosis failed to resume as anticipated. Follicles injected with anti-THBS1 antibody also showed reduced granulosa cell layer expansion, endothelial cell invasion, and capillary formation when compared to control IgG-injected follicles. Overall, these findings support a critical role for THBS1 in follicular angiogenesis, with implications for both successful ovulation and corpus luteum formation.
PubMed: 31787928
DOI: 10.3389/fendo.2019.00727 -
Reproductive Medicine and Biology Mar 2004Progesterone production of human cultured luteinizing granulosa cells was reported to be modified by extracellular matrix, suggesting that extracellular matrix...
Progesterone production of human cultured luteinizing granulosa cells was reported to be modified by extracellular matrix, suggesting that extracellular matrix regulates luteinization of granulosa cells after ovulation. In the present study, the relationship among laminin, fibronectin, progesterone and estradiol in follicular fluid along with oocyte quality was analyzed to estimate the physiological role of extracellular matrix in follicular luteinization and oocyte quality during ovulation. Follicular fluid was collected at oocyte pick-up from the patients undergoing fertilization treatment and intracytoplasmic sperm injection. The concentrations of laminin, fibronectin, progesterone and estradiol in the follicular fluid were measured by enzyme immunoassay and radioimmunoassay. The morphology of oocytes were also assessed during the procedure of intracytoplasmic sperm injection and was classified into normal and abnormal groups. The fibronectin concentration was higher in the normal ooplasm group than in the abnormal group, but it did not correlate with estradiol or progesterone concentration. However, laminin concentration significantly correlated with that of progesterone, but not with cytoplasm morphology of oocytes. There was no difference in estradiol or progesterone concentration between the normal and abnormal groups. These findings suggest that extracellular matrix plays some roles in regulating human granulosa cell luteinization and oocyte quality during ovulation. (Reprod Med Biol 2004; : 43-49).
PubMed: 29699183
DOI: 10.1111/j.1447-0578.2004.00051.x -
Reproduction & Fertility Feb 2023Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting GnRH secretion in mammals. Kisspeptin and its receptor (KISS1R) are...
Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting GnRH secretion in mammals. Kisspeptin and its receptor (KISS1R) are also expressed in certain peripheral tissues including gonads, suggesting intra-gonadal roles. Such actions at the level of the bovine ovary have not been explored previously. The current aims were to determine whether KISS1 and its receptor (KISS1R) are expressed in the bovine ovary and whether kisspeptin or a kisspeptin antagonist can modulate ovarian steroid production by cultured ovarian cells. Granulosa (GC) and theca interna (TC) were collected from antral follicles (3-18 mm) categorized into five class sizes. Early, mid and regressing corpora lutea (CL) were also collected for RT-qPCR analysis of KISS1 and KISS1R expression. Bovine TC and GC cultured under both non-luteinizing (serum-free) and luteinizing (serum-supplemented) conditions were treated for 4 days with kisspeptin-10 (10-10-10-6M) or kisspeptin antagonist (p234; 10-10-10-6M), alone and in combination with either FSH (GC), LH (TC) or forskolin (luteinized GC/TC). Steroid secretion (GC: oestradiol, progesterone; TC: androstenedione, progesterone; luteinized GC/TC: progesterone) was measured by ELISA and viable cell number determined by neutral red uptake assay. KISS1 and KISS1R transcripts were detected in TC, GC and CL with significant differences between follicle categories and CL stages. However, neither kisspeptin-10 nor kisspeptin antagonist affected steroid secretion or viable cell number in any of the four ovarian cell culture models. As such, the hypothesis that kisspeptin has a direct intra-ovarian role to modulate follicular or luteal steroidogenesis, or cell proliferation/survival, is not supported.
PubMed: 36745024
DOI: 10.1530/RAF-22-0088 -
F&S Reports Jun 2023I describe how we identified the need to block the luteinizing hormone (LH) surge when trying to control the processes of luteinization and ovulation within the clinic....
I describe how we identified the need to block the luteinizing hormone (LH) surge when trying to control the processes of luteinization and ovulation within the clinic. The first step, in fact, was using ovarian ultrasound evaluation of follicular development in the natural cycle (published in 1979) and then when the ovary was stimulated with exogenous follicle stimulating hormone. We observed that induced multiple follicular development often led to "premature" LH surges-which occurred before the leading follicle had achieved normal preovulatory dimensions. The work required both ovarian ultrasound and reliable radioimmunoassays, which were not always available. When early work with gonadotropin releasing hormone agonists showed that they could suppress LH activity, it was the logical step to try to use them to perform that task during the induction of multiple follicular development. High frequency administration of the gonadotropin releasing hormone-agonist successfully achieved sustained LH suppression through the follicular phase allowing clinical control of luteinization and ovulation.
PubMed: 37223758
DOI: 10.1016/j.xfre.2022.11.007