Publications

Publications

Ovulation A Sign Of Health: Understanding Reproductive Health In A New Way
Author: Author: Pilar Vigil MD, PhD, FACOG, Contributors: Juan Pablo del Río MD, Natalia Molina BMed, Pedro Gutiérrez MD, Carolina Lyon Nrs, Yanara Bernal Nrs, Felipe G. Serrano BSc,. MSc (2019)

Abstract/Summary
This text analyzes the anatomy of ovulation and the structures involved in this process. It reviews the role of the central nervous system and its communication through the neuroendocrine axis with the gonads and endocrine glands involved in ovulation. The concept of ovarian activity in the lifetime of women, the events that occur in intrauterine life, puberty, and during the reproductive age are also discussed. It analyzes the concept of the fertile window and the processes that surround it, mentioning certain biomarkers. Special relevance was given to the role of cervical mucus as a tool for recognizing ovulation. Also, the relationship between hormones and the brain is mentioned. Finally, in relation to future perspectives, we expose the need for more research in order to improve women’s health and well-being, recognizing ovulation as a sign of health.

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Ovulation, A Sign of Health, The Linacre Quarterly
Author: Vigil P., Lyon C., Flores B., Rioseco H., and Serrano F.G. (2017)

Abstract/Summary
Summary: The ovarian continuum is a process that occurs during a woman’s lifetime. It begins during intrauterine life with fertilization and ends with menopause. This process can be greatly affected by different conditions such as changes in hormonal levels and illnesses. Therefore, understanding and promoting the knowledge and use of biomarkers of ovulation in women is a key aspect to consider when evaluating their health status. The knowledge and education about the ovarian continuum should be taken into account as a powerful tool for women and medical professionals.

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Insulin Sensitivity and Testicular Function in a Cohort of Adult Males Suspected of Being Insulin-Resistant [Frontiers in Public Health]
Author: Contreras P., Vigil P., and Salgado A.M. (2017)

Abstract/Summary
A cohort of 141 males (18-80 yo, 42.9±12.9) suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were considered IR when their Steady State Plasma Glucose (SSPG) was ≥ 150 mg/dL and Non-Insulin Resistant (NIR) when their SSPG was < 150 mg/dL; similarly, the subjects were labeled as Hypogonadal (HYPOG) when their total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when their total testosterone was > 3.0 ng/mL. Subjects n=141 IR n=94 (66.66%) NIR n=47 (33.33%) HYPOG n= 37 (26,24%) 30 7 EUG n=104 (73.76%) 64 40 Chi-square was 4.69 and p was 0.0303, indicating a significant interdependence between insulin resistance and hypogonadism. Age (>43 yo) predicted hypogonadism (AUROC 0.606, p=0.0308). Neither Weight nor BMI predicted hypogonadism, while Waist Perimeter (>110 cm) was a predictor of hypogonadism (AUROC 0.640, p=0.009). SSPG (>224 mg/dL) was a significant predictor of hypogonadism (AUROC 0.709, p=0.002). Age did not predict insulin resistance, while Weight (>99 kg), BMI (>29), and specially, Waist Perimeter (> 100 cm, AUROC 0.812, p< 0.0001) were all significant predictors of insulin resistance. In conclusion, Waist Perimeter predicted both insulin resistance (> 100 cm) and hypogonadism (> 110 cm), suggesting that the first hit of abdominal obesity is insulin resistance and the second hit is male hypogonadism.

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Steroid Hormones and the Action in Women’s Brain [Frontiers in Public Health]
Author: Alliende I., Serrano F.G., Molina N., Del Río J.P., and Vigil P. (2017)

Abstract/Summary
Sex hormones act on steroid receptors all through the body including the nervous system at the synaptic level at which they exert their action through membrane receptors. They are produced in peripheral endocrine organs and additionally by glia and neurons in different brain areas. In this way, estrogen, progesterone and their metabolites play a role in the organization and activation of the central neural system. This role is carried out through the regulation of different neurotransmitters such as GABA, serotonin, dopamine, and glutamate. In general, estrogens enhance serotonin and dopamine neurotransmission and progesterone interacts directly through GABA receptors, all of which has been related to affective disorders, mood changes and behavior. In the present review, we analyze how hormonal fluctuations that occur during women’s life, the menstrual cycle and during certain pathological conditions (related to hormonal imbalances) influence changes in behavior, mood and mental disorders such as depression. Therefore, this review emphasizes the importance of having a hormonal balance during different life stages in order to improve mental health conditions. For this, monitoring hormonal levels according to a woman’s age and ovulatory status are essential for a correct diagnosis and treatment of behavioral and /or mood disorders. The knowledge of the action of steroid hormones in the brain will give women and health providers and important tool for improving their health and wellbeing from menarche until menopause.

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The Sperm Journey from the Cervix to the Site of Fertilization; a Predetermined Encounter [Imago Homini 24: 71-82]
Author: Vigil P., Valdés-Undurraga I., Del Río J.P., and Serrano F.G. (2017)

Abstract/Summary
Sperm interact with various microenvironments, generating conditions for sperm capacitation and acrosome reaction in the right place and time. Such events are highly synchronized to ensure fertilization. This review describes and analyzes the various changes sperm experience during transport through the female genital tract: the infuence of cervical, endometrial and oviductal secretions, interaction with the epithelium, and hormonal effects on sperm. Molecules in the microenvironments with which sperm interact include hormones, neurotransmitters, and other metabolites. Physiological events of gamete membrane fusion should be considered by basic and ap- plied researchers working in reproductive biology.

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Influence of sex steroid hormones on the adolescent brain and behavior: An update [The Linacre Quarterly, 83(3), 308-329]
Author: Pilar Vigil, Juan Pablo del Río, Ba ́rbara Carrera, Florencia C. Ara ́nguiz, Hernán Rioseco & Manuel E. Cortés (2016)

Abstract/Summary
The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and com- pounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders.

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Self-identification of the clinical fertile window and the ovulation period [Fertility & Sterility, 103(5), 1319–1325]
Author: Ecochard, R., Duterque, O., Leiva, R., Bouchard, T., & Vigil, P. (2015)

Abstract/Summary
The self-identification of the biological fertile window by the observation of any type of cervical mucus provides 100% sensitivity but poor specificity, yielding a clinical fertile window of 11 days. However, the identification of the biological fertile window by peak mucus (defined as clear, slippery, or stretchy mucus related to estrogen) yielded 96% sensitivity and improved specificity. The appearance of the peak mucus preceded the biological fertile window in less than 10% of the cycles. Likewise, this type of mucus identified the ovulation window with 88% sensitivity.

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The role of kisspeptin on the onset of puberty and on the ovulatory mechanism: A minireview [Journal of Pediatric and Adolescent Gynecology, 28(5), 286–291]
Author: Cortés, M. E., Carrera, B., Rioseco, H., del Río, J. P., & Vigil, P. (2015).

Abstract/Summary
The onset of puberty has been a fascinating topic for reproductive endocrinologists for decades; however, its underlying physiological mechanisms have remained elusive until recently. The discovery and understanding of the effects exerted by the peptide hormone kisspeptin have shed light on this research area. This review is aimed to discuss the functions of kisspeptin, with special focus on its role in the onset of puberty and in the ovulatory mechanism. The points under discussion are (1) the characteristics of kisspeptin and its receptor, (2) the relevance of this hormone and its interaction with leptin in the onset of puberty, (3) the role of kisspeptin in the ovulatory mechanism based on its differential expression at hypothalamic nuclei, which is modulated by sex steroid hormones, and (4) the clinical relevance of kisspeptin and its antagonists in new therapeutic strategies for the treatment of various reproductive pathologies. All of this explains the revolution that kisspeptin has caused among researchers working in the field of gynecological endocrinology and reproductive biology.

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The effects of hormonal contraceptives on glycemic regulation [The Linacre Quarterly, 81(3), 209–218]
Author: Cortés, M. E., & Alfaro, A. a. (2014)

Abstract/Summary
A number of side effects have been linked to the use of hormonal contraceptives, among others, altera- tions in glucose levels. Hence, the objective of this mini-review is to show the main effects of hormonal contraceptive intake on glycemic regulation. First, the most relevant studies on this topic are described, then the mechanisms that might be accountable for this glycemic regulation impairment as exerted by hormonal contraceptives are discussed. Finally, we briefly discuss the ethical responsibility of health pro- fessionals to inform about the potential risks on glycemic homeostasis regarding hormonal contraceptive intake.

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Highly symmetrical crystallization in six rectilinear and well- defined axes found in bovine cervical mucus obtained at oestrus: a finding. [Revista de La Facultad de Medicina Veterinaria y de Zootecnia, 61(2), 167-170]
Author: Cortés, M. E., González, F., Hauyón, R., & Vigil. Pilar. (2014)

Abstract/Summary
Bovine cervical mucus (BCM) is important for selection and transport of spermatozoa. When air-dried, BCM obtained at oestrus exhibits arborescent crystallizations, among other arrangements. Considering the relevant endocrine and reproductive information indirectly obtained from BCM crystallization, a morphological investigation was carried out to study its crystalline patterns. BCM samples were collected from healthy Holstein Friesian heifers at oestrus, their crystalline patterns photographed and its morphology analyzed. The majority of the crystallizations obtained showed the typical tree-like patterns reported for BCM. However, a highly symmetrical arrangement was found, characteri- zed by a star-like morphology with six straight, highly defined axes that protrude from the same central point, forming 60o angles. In terms of current knowledge, this short report is the first to show this crystallization geometry in BCM, which, additionally, is remarkably similar to P6B mucus reported for periovulatory human cervical mucus. Even though the role of mucus presenting this type of crystallization is as yet unknown for bovines, its possible functions are also briefly discussed here.

Key words: Bovine cervical mucus, crystallization, oestrus, P6B mucus.

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Crystallization of Bovine Cervical Mucus at Oestrus : An Update [Rev Med Vet, 28, 103-16]
Author: Cortés, M. E., González, F., & Vigil, P. (2014)

Abstract/Summary
Bovine cervical mucus changes its biochemical composition and biophysical properties due to the variations in sex steroid levels during the oestrous cycle. As a consequence of oestro- gen rise, cervical mucus is produced in larger amounts at oestrus—a stage also characterized by an increase in mucus crystallization when observed under light microscopy. The objective of this article is to provide an updated review of the main aspects regarding crystallization of bovine cervical mucus. First, it makes reference to the composition of cervical mucus and the critical functions that this secretion exerts on bovine reproductive physiology, as well as in other species. Then, the article deals with the phenomenon of crystallization observed in cervical mucus, describing the main models used to classify the crystalline patterns ob- servable in mucus at oestrus stage (some of them resembling ferns, palm leaves and stellar patterns, among others). Finally, it addresses the importance of the phenomenon of cervical mucus crystallization for the understanding of bovine reproductive physiology.

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The Importance of Fertility Awareness in the Assessment of a Woman’s Health: A Review [The Linacre Quarterly, 79(4), 426–450]
Author: Vigil, P., Blackwell, L. F., & Cortés, M. E. (2012)

Abstract/Summary
Fertility awareness constitutes fundamental knowledge for every woman and is an important tool for health professionals. The objective of this review is to show how fertility awareness can be useful in the assessment of a woman’s health. The main techniques for detecting ovulation are explained, and then the events that characterize a normal menstrual cycle are discussed. The relevance of cervical mucus from the perspective of female fertility is highlighted. Finally, the usefulness of fertility awareness 1) to identify fertile and infertile periods, 2) to help to detect several pathologies, and 3) in regards to how it exerts an important role in the success of programs in education for affectivity and sexuality are discussed.

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Modulation of spermatozoon acrosome reaction [Biological Research, 44, 151–159]
Author: Vigil, P., Orellana, R. F., & Cortés, M. E. (2011)

Abstract/Summary
Spermatozoon acrosome reaction is an exocytotic event of the utmost importance for the development of mammalian fertilisation. Current evidence shows that the triggering of the acrosome reaction (AR) could be regulated by the action of diverse compounds, namely, metabolites, neurotransmitters and hormones. The aim of the present review is to describe the modulating effects of several compounds that have been classified as inductors or inhibitors of acrosome reaction. Among AR inductors, it is necessary to mention progesterone, angiotensin II, atrial natriuretic peptide, cathecolamines, insulin, leptin, relaxin and other hormones. Regarding the inhibitors, oestradiol and epidermal growth factor are among the substances that retard AR. It is worth mentioning that gamma-aminobutyric acid, a neurotransmitter known to be an inhibitor in the central nervous system, has been shown to induce AR. The multiple hormones located in the fluids of the female reproductive tract are also likely to act as subtle regulators of AR, constituting a fundamental aspect for the development of successful fertilisation. Finally, it is necessary to emphasise that the study of regulation exerted by hormones and other compounds on AR is essential for further understanding of mammalian reproductive biology, especially spermatozoon physiology.

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Endocrine Modulation of the Adolescent Brain: A Review [Journal of Pediatric and Adolescent Gynecology, 24, 330–337]
Author: Vigil, P., Orellana, R. F., Cortés, M. E., Molina, C. T., Switzer, B. E., & Klaus, H. (2011)

Abstract/Summary
Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.

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Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings) [Human Reproduction Update, 17(2), 141–58]
Author: Brown, J. B. (2010)

Abstract/Summary
There are many types of ovarian activity that occur in women. This review provides information on the relationship between the hormone values and the degree of biological response to the hormones including the frequency and degree of uterine bleeding. The continuous process is termed the ‘Continuum’ and is thus similar to other processes in the body.

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Scanning electron and light microscopy study of the cervical mucus in women with polycystic ovary syndrome [Journal of Electron Microscopy, 58(1), 21–27]
Author: Vigil, P., Cortés, M. E., Zuñiga, A., Riquelme, J., & Ceric, F. (2009).

Abstract/Summary
Two types of cervical mucus are recognized, oestrogenic and gestagenic. These are constituted by different subtypes, and their characteristics change depending on variations in the hormonal levels and on the existence of several pathologies. Our aim was to identify the ultrastructure and crystallization characteristics of the cervical mucus in women suffering from polycystic ovary syndrome, and to compare these characteristics with those of normal control women. Cervical mucus samples were taken from 10 women, 4 control group women (with normal ovulatory menstrual cycles) and 6 suffering from polycystic ovary syndrome (2 with ovulatory and 4 with anovulatory cycles). This mucus was characterized according to its ultrastructure and crystallization. The type of mucus obtained was related to the levels of oestradiol and progesterone present when the samples were taken. As regards mucus ultrastructure, differences were found between the control women and those with polycystic ovary syndrome and anovulatory menstrual cycles. Such variations were evident in the type of mesh and the average diameter of the mucus pores. Mucus crystallization in control women showed the usual oestrogenic disposition: fern-like (L, P2), rectilinear (S) or a hexagonal structure (P6). On the other hand, in women with polycystic ovary syndrome, indefinite mucus crystallizations were found, as well as crystallization patches resembling oestrogenic and gestagenic-like mucus. This study shows that the ultrastructure and crystallization characteristics of the cervical mucus in polycystic ovary syndrome women are different from those of control women. The latter would be dependent on their levels of oestradiol and progesterone.

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Physiological action of oestradiol on the acrosome reaction in human spermatozoa. [Andrologia, 40, 146–151]
Author: Vigil, P., Toro, A., & Godoy, A. (2007)

Abstract/Summary
The acrosome is a secretory vesicle located in the sperm head. The acrosome reaction consists in the fusion of the sperm plasma membrane with the external acrosomal membrane. It has been observed that this reaction does not take place in spermatozoa incubated in cervical mucus, hydrogel that contains high concentrations of oestradiol in the peri-ovulatory period. The objective of the present study was to analyse the influence of oestradiol on the acrosome reaction in human spermatozoa to evaluate the possible inhibitory effect of this hormone. Spermatozoa were incubated in progesterone (10.1 nmol l−1); oestradiol plus progesterone (oestradiol at 840 pmol l−1 and progesterone at 10.1 nmol l−1), oestradiol (840 pmol l−1) and control (without steroidal hormones) for 30 min, 60 min, 240 min and 24 h. The acrosome reaction was evaluated by stain with Hoechst 33258 and fluorescein isothiocyanate-conjugated Pisum sativum agglutinin lectin. Progesterone-incubated spermatozoa showed the highest percentage of acrosome reaction (P < 0.05). Spermatozoa incubated with oestradiol and oestradiol plus progesterone showed the lowest percentage of acrosome reaction. The present study demonstrates the inhibitory role of oestradiol on the acrosome reaction, stimulated by progesterone in human spermatozoa under physiological conditions.

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Usefulness of Monitoring Fertility from Menarche [Journal of Pediatric and Adolescent Gynecology, 19(3), 173–179]
Author: Vigil, P., Ceric, F., Cortés, M. E., & Klaus, H. (2006)

Abstract/Summary
The concept of the ovarian cycle as a continuum considers that all types of ovarian activity encountered during the reproductive life are responses to different environmental conditions in order to ensure the health of the woman. During the normal ovulatory cycle, a series of sequential events have to occur in a highly synchronized manner. Fertility awareness is useful in helping women to identify the different stages of their reproductive life cycle. Fertility awareness is also a valuable tool in helping women to identify gynecological disorders. Persistence of irregularities within the mucus patterns and the menstrual cycle should be of concern to women presenting with these problems. These irregularities may be due to obstetrical, endocrine, gynecological or iatrogenic disorders. Insight into early pregnancy complications, ovulatory dysfunction and pelvic inflammatory disease can be ascertained from abnormalities within the menstrual cycle and mucus pattern. Thus, fertility awareness will also enable the recognition and early treatment of several metabolic, endocrine and infectious diseases.

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Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV [Hum Reprod., 31(2), 445-53]
Author: Leonard F. Blackwell; Pilar Vigil; Maria Elena Alliende; Simon Brown; Mario Festin; Delwyn, G. Cooke

Abstract/Summary
The relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period

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