Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth.

Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8-12 mg/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6-11.2 mg/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.

Functional anatomy of the female reproductive system of the American lobster (Homarus americanus).

Light microscopy studies of the female American lobster Homarus americanus reproductive system are essentially nonexistent or outdated. Based on samples taken in the spring, summer, and autumn from the southern Gulf of St. Lawrence between 1994 and 2014, and using a combination of histological and scanning electron microscope techniques, we propose an ovarian cycle with 10 stages, identifying for the first time a recovery stage. Also, an atypical resorption stage, characterized by massive reabsorption of mature oocytes, is occasionally observed during summer months. The oviducts are composed of connective tissue (elastic and collagen fibers) with no muscle or secretory activities. Their epithelium shows a cyclic pattern and phagocytosis activities linked to spawning. Although the role of the seminal receptacle is to store and protect semen, free spermatozoa (i.e., without the spermatophoric wall and the acellular gelatinous substance that constitute the semen) were also observed in its posteriolateral grooves immediately prior to spawning, which is consistent with an external fertilization mechanism at the seminal receptacle. Unexpectedly, free spermatozoa were observed externally near two pore-like structures located on the gonopore's operculum, not at the seminal receptacle, after spawning; hence, more work is needed to fully understand the fertilization mechanism for the American lobster.

The Effects of a Genital Vibratory Stimulation Device on Sexual Function and Genital Sensation.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a genital vibratory stimulation device in improving sexual function in women with arousal and orgasm disorders. METHODS: In this single-arm, prospective study, baseline and 1- and 3-month assessments were performed to evaluate women with sexual arousal and/or orgasmic disorders, who received therapy using a genital vibratory stimulation device. Sexual function, satisfaction, and distress were evaluated using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale, and the Female Intervention Efficacy Index questionnaires. Genital sensation was evaluated using quantitative sensory testing. RESULTS: Seventy women, aged 19 to 64 years, were evaluated from October 2009 to August 2013. Forty-seven (67.1%) and 37 (52.9%) women completed 1- and 3-month follow-ups, respectively. The FSFI arousal and orgasm domain scores and total FSFI scores improved at 1 and 3 months (P < 0.001 for all outcomes). Mean (SD) total FSFI scores increased from 20.04 (4.65) (baseline) to 25.03 (5.21) (1 month) to 26.66 (5.42) (3 months; both Ps < 0.0001). Female Sexual Distress Scale scores reflected significantly decreased distress at 1 (P = 0.0006) and 3 (P < 0.0001) months compared with baseline and at 3 months compared with 1 month (P = 0.03). Neurological sensation was increased at all genital sites at 1 and 3 months (P < 0.0001 for all). After adjustment for age, there was a significant interaction between arousal domain scores and clitoral and right labial sensation. At 3 months, perceptions of increased vaginal lubrication, orgasm, and genital sensation were reported by 67.5%, 65.0%, and 82.5% of the participants. No major adverse events were noted. CONCLUSIONS: Genital vibratory stimulation device use resulted in uniform improvements in sexual function, satisfaction, sexually related distress and genital sensation.

Vitamin D in human reproduction: a narrative review.

BACKGROUND: Special attention has been given to the effect of vitamin D supplementation on fertility outcomes in both sexes. AIMS: The purpose of this narrative review was to elucidate the role of vitamin D in male and female reproduction, providing current evidence from both animal and human studies. MATERIALS AND METHODS: Using PubMed and Medline, we searched for publications during the last 30 years regarding the role of vitamin D in human reproduction. RESULTS: Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders. In women, vitamin D status has been associated with in vitro fertilization (IVF) outcome, features of polycystic ovarian syndrome (PCOS) and endometriosis. Although several data converge towards a beneficial effect of vitamin D supplementation in metabolic disturbances in women with PCOS, a significant knowledge gap precludes the establishment of a clear cause-effect relationship. In men, vitamin D status has been associated with semen quality and sperm count, motility and morphology. There is evidence for a favourable effect of vitamin D supplementation on semen quality, testosterone concentrations and fertility outcomes. DISCUSSION: Studies with superior methodological characteristics are needed in order to establish a role for vitamin D on the treatment of female and male infertility. CONCLUSIONS: Recent data on vitamin D provide new insights in the complex pathogenesis and treatment of infertility.

Localization of ghrelin and its receptor in the reproductive tract of Holstein heifers.

The aim of this experiment was to localize the mRNA and protein of ghrelin and its active receptor, growth hormone secretagogue 1A (GHS-R1A), within the reproductive tract of dairy cattle. Ghrelin is an orexigenic hormone that has been identified as a potent regulator of energy homeostasis. Recent evidence suggests that ghrelin may also serve as a metabolic signal to the reproductive tract. Ghrelin and GHS-R1A have been identified in the reproductive tract of several species, including humans, mice, and rats. However, ghrelin and GHS-R1A expression have not been described within bovine reproductive tissues. Therefore, the ampulla, isthmus, uterine body, corpus luteum, and follicles were harvested from 3 Holstein heifers (15.91±0.07 mo of age) immediately following exsanguination. Duodenum and hypothalamus were collected as positive controls for ghrelin and GHS-R1A, respectively. Tissues were fixed in 10% formalin and embedded in paraffin for microscopy. Additional samples were stored at -80°C for detection of mRNA. Ghrelin and GHS-R1A mRNA and protein were observed in all tissue types within the reproductive tract of dairy heifers; however, expression appeared to be cell specific. Furthermore, ghrelin protein appeared to be localized to the cytoplasm, whereas GHS-R1A protein was found on the plasma membrane. Within the reproductive tissues, ghrelin mRNA and protein were most abundantly expressed in the ampulla of the oviduct. Concentrations of GHS-R1A were lower than those of ghrelin but differed between tissues. This is one of the first studies to provide molecular evidence for the presence of ghrelin and GHS-R1A within the entire reproductive tract. However, implications for fertility remain to be determined.

Fisiopatología y tratamiento de la atrofia genitourinaria en mujeres / Pathophysiology and therapy of urogenital atrophy in women

La involución del tracto genital femenino refleja su integración con los cambios que sufre el eje hipotálamo-hipofisario-ovárico. El descenso de los niveles de estradiol conlleva una serie de efectos adversos, incluidos los relativos a las vías urinarias inferiores. El cambio más importante es la atrofia vaginal: la mucosa vaginal se vuelve más fina y seca, lo cual puede producir incomodidad vaginal, sequedad, quemazón, prurito y dispareunia. El epitelio vaginal puede presentar cambios inflamatorios y ser un factor que contribuya a los síntomas urinarios, tales como frecuencia, urgencia, disuria, incontinencia, e infecciones recurrentes. Por otra parte, se ha sugerido que los niveles bajos de estrógenos pueden afectar los tejidos periuretrales y contribuir a la laxitud de la pelvis y la incontinencia de esfuerzo. Relacionados con el hipoestrogenismo, los cambios en el pH y la flora vaginal pueden predisponer a las mujeres posmenopáusicas a las infecciones del tracto urinario. La terapia hormonal local en forma de cremas, comprimidos o supositorios es la base del tratamiento de la atrofia genital. Además, otras vías de administración de hormonas, tanto local como sistémica, también han demostrado ser válidas. Sin embargo, a pesar de que los beneficios del reemplazo con estrógenos en la prevención de la atrofia vaginal y la reducción de la incidencia de los síntomas están bien establecidos, este tipo de tratamiento está contraindicado en algunas mujeres y no es una opción aceptable para otras. Pero además, la ruta óptima de administración del tratamiento hormonal, el régimen, las dosis, y las alternativas no hormonales para mejorar los síntomas y la calidad de vida de la población posmenopáusica no han sido completamente estudiados. Esta revisión se centra en los cambios del envejecimiento vaginal e intenta presentar una sinopsis de la fisiopatología y el tratamiento de la atrofia vaginal y la vaginitis atrófica. (AU)

Fisiopatología y tratamiento de la atrofia genitourinaria en mujeres / Pathophysiology and therapy of urogenital atrophy in women

La involución del tracto genital femenino refleja su integración con los cambios que sufre el eje hipotálamo-hipofisario-ovárico. El descenso de los niveles de estradiol conlleva una serie de efectos adversos, incluidos los relativos a las vías urinarias inferiores. El cambio más importante es la atrofia vaginal: la mucosa vaginal se vuelve más fina y seca, lo cual puede producir incomodidad vaginal, sequedad, quemazón, prurito y dispareunia. El epitelio vaginal puede presentar cambios inflamatorios y ser un factor que contribuya a los síntomas urinarios, tales como frecuencia, urgencia, disuria, incontinencia, e infecciones recurrentes. Por otra parte, se ha sugerido que los niveles bajos de estrógenos pueden afectar los tejidos periuretrales y contribuir a la laxitud de la pelvis y la incontinencia de esfuerzo. Relacionados con el hipoestrogenismo, los cambios en el pH y la flora vaginal pueden predisponer a las mujeres posmenopáusicas a las infecciones del tracto urinario. La terapia hormonal local en forma de cremas, comprimidos o supositorios es la base del tratamiento de la atrofia genital. Además, otras vías de administración de hormonas, tanto local como sistémica, también han demostrado ser válidas. Sin embargo, a pesar de que los beneficios del reemplazo con estrógenos en la prevención de la atrofia vaginal y la reducción de la incidencia de los síntomas están bien establecidos, este tipo de tratamiento está contraindicado en algunas mujeres y no es una opción aceptable para otras. Pero además, la ruta óptima de administración del tratamiento hormonal, el régimen, las dosis, y las alternativas no hormonales para mejorar los síntomas y la calidad de vida de la población posmenopáusica no han sido completamente estudiados. Esta revisión se centra en los cambios del envejecimiento vaginal e intenta presentar una sinopsis de la fisiopatología y el tratamiento de la atrofia vaginal y la vaginitis atrófica.

Effects of phytoestrogen supplementation in the feed on the shell gland of laying hens at the end of the laying period.

Shell quality decreases as laying hens age and the aim of present study was to investigate how a supplement of daidzein, a natural phytoestrogen in soya, affects key factors in the shell gland and eggshell quality in late-stage laying hens. Hybrids of Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB), received either a daidzein diet (50 mg/kg feed) or a control diet from 60 to 72 weeks of age. Both the total number of capillaries and capillaries with carbonic anhydrase (CA) activity were higher in the LSL hybrid than in the LB. After daidzein supplementation the number of CA positive capillaries was unaffected in the LSL but increased in the LB hybrid indicating a higher sensitivity to daidzein in this hybrid. Estrogen receptor alpha and beta (ERα, ERß) were localized and the complete picture of the two ERs can now be described in shell gland of domestic hens. Nuclear and cytoplasmic staining was generally stronger for ERß, while membrane associated staining was present only for ERα. Interestingly, capillary endothelium contained only ERß and since estrogen regulation of CA is well documented, the presence of an endothelial ER provides one possible route for the increase in CA positive capillaries found in LB hybrids. Eggshell quality or egg production was not affected by daidzein supplementation. The hybrids used in this study showed anatomical differences and reacted differently to daidzein supplementation, but if this can be explained by the divergences in ERß localization noted between the hybrids remains to be clarified.

Neonatal diethylstilbestrol exposure disrupts female reproductive tract structure/function via both direct and indirect mechanisms in the hamster.

We assessed neonatal diethylstilbestrol (DES)-induced disruption at various endocrine levels in the hamster. In particular, we used organ transplantation into the hamster cheek pouch to determine whether abnormalities observed in the post-pubertal ovary are due to: (a) a direct (early) mechanism or (b) an indirect (late) mechanism that involves altered development and function of the hypothalamus and/or pituitary. Of the various disruption endpoints and attributes assessed: (1) some were consistent with the direct mechanism (altered uterine and cervical dimensions/organization, ovarian polyovular follicles, vaginal hypospadius, endometrial hyperplasia/dysplasia); (2) some were consistent with the indirect mechanism (ovarian/oviductal salpingitis, cystic ovarian follicles); (3) some were consistent with a combination of the direct and indirect mechanisms (altered endocrine status); and (4) the mechanism(s) for one (lack of corpora lutea) was uncertain. This study also generated some surprising observations regarding vaginal estrous assessments as a means to monitor periodicity of ovarian function in the hamster.

Effect of Asparagus racemosus rhizome (Shatavari) on mammary gland and genital organs of pregnant rat.

Asparagus racemosus (AR) Willd (family Liliaceae) is commonly known as Shatavari. The alcoholic extract of its rhizome was administered orally to adult pregnant female albino rats at a dose of 30 mg/100 g body weight, daily for 15 days (days 1-15 of gestation). The macroscopic findings revealed a prominence of the mammary glands, a dilated vaginal opening and a transversely situated uterine horn in the treated group of animals. The weight of the uterine horns of the treated group was found to be significantly higher (p < 0.001) but the length was shorter (p > 0.01). Microscopic examination of the treated group showed proliferation in the lumen of the duct of mammary gland. It was obliterated due to hypertrophy of ductal and glandular cells. Hyperplasia of the glandular and muscular tissue and hypertrophy of the glandular cells were observed in the genital organs. The parenchyma of the genital organs showed abundant glycogen granules with dilated blood vessels and thickening of the epithelial lining. The oviduct in the treated group showed hypertrophied muscular wall, whereas the ovary revealed no effect of the drug. The results suggest an oestrogenic effect of Shatavari on the female mammary gland and genital organs.

The role of paf in embryo physiology.

Embryo-derived paf (1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is produced by de novo synthesis. This synthesis commences soon after fertilization and persists throughout the preimplantation phase. Paf is produced and released by the embryos of all mammalian species studied to date. Its release from the embryo involves binding to extracellular albumin in a manner that protects paf from enzymatic degradation. Released paf causes a range of alterations in maternal physiology, including platelet activation, changes in oviductal, endometrial and maternal immune function. Paf also acts in an autocrine fashion as a trophic/survival factor for the early embryo. In vitro, supplementation of culture media with paf improves embryo development. Embryo-derived paf's autocrine actions are transduced by 1-o-phosphatidylinositol-3-kinase, which induces characteristic calcium transients within the early embryo. The calcium transients require both the influx of external calcium and release of inositol trisphosphate-dependent internal calcium stores. Buffering these transients compromised embryo development in a manner that was reversed by exogenous paf. Assisted reproductive technologies compromise the production of paf by some embryos and retard the expression of the paf receptor. This deprivation of paf's action is one of the factors limiting the survivability of embryos produced by assisted reproductive technologies. Paf is one of several autocrine and paracrine trophic/survival factors that act on the early embryo. These factors probably act cooperatively and may, to some degree, be mutually redundant. As the earliest-released and the best-described embryotrophin, paf provides an important exemplar for understanding the role of ligand-mediated trophic support of the early embryo.

Phytoestrogens alter the reproductive organ development in the mink (Mustela vison).

The aim of the present study was to examine the reproductive effects of two perorally applied phytoestrogens, genistein (8 mg/kg/day) and beta-sitosterol (50 mg/kg/day), on the mink (Mustela vison) at human dietary exposure levels. Parental generations were exposed over 9 months to these phytoestrogens and their offspring were exposed via gestation and lactation. Parents and their offspring were sampled 21 days after the birth of the kits. Sex hormone levels, sperm quality, organ weights, and development of the kits were examined. The exposed females were heavier than the control females at the 1st postnatal day (PND). The control kits were heavier than the exposed kits from the 1st to the 21st PND. Phytoestrogens did not affect the organ weights of the adult minks, but the relative testicular weight of the exposed kits was higher than in the control kits. The relative prostate weight was higher and the relative uterine weight lower in the beta-sitosterol-exposed kits than in the control kits. Moreover, the plasma dihydrotestosterone levels were lower in the genistein-exposed male kits compared to the control male kits. This study could not explain the mechanisms behind these alterations. The results indicate that perinatal phytoestrogen exposures cause alterations in the weight of the reproductive organs of the mink kits.

Alfalfa as a single dietary source for molt induction in laying hens.

Molting is a process by which a hen's reproductive tract is rejuvenated prior to the beginning of a laying cycle. This process is often artificially induced in commercial settings in order to extend the productive life of a flock of hens. The most common method for the induction of molt is feed withdrawal for a period of several days. It has been noted that feed withdrawal, while effective in inducing molt and allowing an adequate reproductive rest period for the hen, may cause deleterious effects on the animal. This has prompted the investigation of alternatives to feed deprivation for the induction of molt in commercial laying hens. This study involved feeding alfalfa to hens to assess its ability to induce molt. Results show that alfalfa meal and alfalfa pelleted diets were equally effective as feed withdrawal in causing ovary weight regression in birds. Molted hens induced by alfalfa diets exhibited postmolt levels of egg production over a twelve week period that were similar to that of hens molted by feed withdrawal. The postmolt eggs laid by hens molted by alfalfa were of comparable quality to eggs from feed deprived hens. Alfalfa, a fibrous feed with low metabolizable energy, may be provided to hens on an ad libitum basis for an effective molt induction that retains comparable egg quality and production.

Neurophysiology and pharmacology of female genital sexual response.

Vaginal sexual arousal is a vasocongestive and neuromuscular event controlled by facilitatory parasympathetic and inhibitory sympathetic inputs. Autonomic preganglionic parasympathetic and inhibitory sympathetic fibers to the vagina and clitoris originate in the spinal cord in the sacral parasympathetic nucleus at the sacral level and in the dorsal gray commissure and the intermediolateral cell column at the thoracolumbar level, respectively. Parasympathetic fibers are conveyed by the pelvic nerve, and sympathetic fibers are conveyed by the hypogastric nerve and the paravertebral sympathetic chain. The activity of these spinal nuclei is controlled by descending projections from the brain and sensory afferens (conveyed in the pudendal, hypogastric, pelvic, and vagus nerves) from the genitalia. A key but unresolved issue concerns the neurotransmitters involved in the control of genital sexual arousal. At the peripheral level, acetylcholine plays a minor role in the regulation of vaginal blood flow, however, recent data suggests that it may be involved in the control of vaginal smooth muscle contractions. Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal, whereas noradrenaline is likely inhibitory. Within the central nervous system, serotoninergic projections from the brain to the spinal cord likely inhibit the induction of genital arousal by peripheral informations (spinal reflex). Although some neurotransmitters regulating the display of sexual behavior have been identified (for example, dopamine), their involvement in the control of genital sexual arousal has not been invested. Anatomical and electrophysiological data point to a contribution of the paraventricular nucleus of he hypothalamus and the median preoptic area, respectively, as key elements in the control of genital arousal. The recent development of models allowing the assessment of vaginal sexual arousal in anesthetized female rats should assist in deciphering the neurochemical pathways controlling vaginal sexual arousal and the development of suitable pharmacological treatment for female sexual dysfunctions.

Sites of female reproductive vulnerability: implications for testing and risk assessment.

All reproductive toxicity testing, whether in vivo or in vitro, should be conducted with consideration of the ultimate use of the data for reproductive risk assessment and the protection of human reproductive health. In this review selected sites of vulnerability in the female reproductive system are identified. These sites of female reproductive vulnerability may be utilized for in vitro toxicity testing assays, and the data from assays may be employed in the hazard identification and hazard characterization steps necessary for reproductive risk assessment. Using biomarkers of female reproductive function derived from in vitro toxicity testing it is possible to define functions that characterize female fecundity. These characterizations of female fecundity may be used to quantitate reproductive risk in human populations.

Knowledge of reproductive physiology and modern contraceptives in rural Peru.

This report is based on fieldwork conducted in a Peruvian community in 1986, which investigated Quechua-speaking Indians' knowledge of the female reproductive organs, perceptions of the way contraceptives work in the body, folk beliefs about conception and menstruation, and opinions about modern contraceptives. The findings reveal that the men have a more accurate knowledge of the female reproductive organs than the women do. However, the women are more knowledgeable about the action of modern contraceptives in the body. Most respondents perceived modern contraceptive methods as the best methods available, but the majority reported using the calendar rhythm method. This preference for rhythm is based on its economic advantage and on its adaptability to folk beliefs about physiology. The men's dominant role in reproductive behavior is related to cultural norms that emphasize traditional gender roles and that prohibit communication about sexual matters between men and women. Educational material, based on the respondents' knowledge of reproduction and taking into account their folk beliefs, might help to decrease the fear of contraceptive side effects and increase understanding of the function of contraceptives.

Physiologic assessment of sexual response in women: the unfulfilled promise.

With the exception of work by Semmens (1979), the clinical value of physiologic measures of female sexual response has not been demonstrated; it almost seems that controlled attempts to apply measures of vaginal muscular tone or blood flow to clinical settings has been jinxed. Hence, this author takes issue with Hatch (1980), who gives the impression that physiologic measures can now be used in clinical applications. The reasons for failure in sex therapy or biofeedback are uncertain, but it may be useful to speculate briefly. Sexual arousal in women is too personal a phenomenon to be objectively assessed during waking states in an "artificial" laboratory context. Orgasmic response is not related to genital muscle tone, but to other unknown anatomic, learning-history, and psychological components. The circumstances under which there is agreement between physiologic and either psychometric or self-reports of arousal or pleasure are complex and interactive. Therefore, physiologic measures of female sexual response may not reflect the subjective experience of women and, taken alone, may be misleading. This conclusion should not surprise anyone, for human beings are truly a "cognitive" species with representational imagery and language. Sexuality is very much "in the frontal lobes," and what we perceive eroticism to mean in a given context is probably much more important than the physiologic and behavioral aspects of actual sexual expression. Despite these problems of employing physiologic measures of female response in clinical settings, research into more basic issues has been quite profitable and heuristic. For example, several common assumptions about female sexuality are now open to question: women are more arousable just prior to menses; Kegel exercises improve orgasm consistency; sex therapy for inhibited arousal and desire is efficacious; there is usually agreement between the physiologic intensity of sexual response and a patient's subjective estimate of that intensity. On the other hand, there is evidence that vaginal engorgement in women remains at a high level after an initial orgasm, thus setting the physiologic stage for consecutive orgasmic responses; sexual arousal can be measured physiologically with acceptable degrees of reliability and specificity; muscle contractions in women during orgasm can be measured with high levels of precision; women respond to direct representations of erotic activity much the way men do; there are cortical "physiologic" signatures of orgasmic response in men and women. Obviously, a number of clinical research issues in female sexuality can now be investigated with physiologic measures.(ABSTRACT TRUNCATED AT 400 WORDS)