Endocrine disrupting chemical Bisphenol A and its potential effects on female health

Background and aimA large number of chemical compounds with endocrine-disrupting activity have been documented. These chemicals are ubiquitous and widely used in many products of our daily lives. Bisphenol A (BPA) is among the most common Endocrine Disrupting Chemical (EDC) that has been used for many years in the manufacture of polycarbonate plastics and epoxy resins. There is growing evidence that exposure to these EDCs poses a possible health risk. This review focuses on the effect of EDCs, in particular, BPA on female reproduction and Polycystic Ovary Syndrome (PCOS), which is the most prevalent endocrine disorder of reproductively aged women.MethodsA relevant literature survey was conducted with Google scholar and Pubmed using several appropriate keywords to select the most relevant studies evaluating the role of endocrine disrupting-chemicals in female reproduction.ResultsThe female menstrual cycle and fertility are very sensitive to hormonal imbalance and alteration in endocrine function during critical times and different stages of lifecycle owing to EDC exposure results in many abnormalities like menstrual irregularities, impaired fertility, PCOS, and Endometriosis among others. BPA is the most extensively studied EDC worldwide and has been strongly associated with female reproductive health.ConclusionEDCs lead to deleterious effects on human health including reproductive health which are of global concern. Exposure to EDCs in early life can elicit disease in adult life and maybe even transgenerational. There is an immediate need to minimize the ill effect of EDCs which can be tackled through the collection of more data to clarify the clinical implications of EDCs.     

Endocrine regulation of posteclosion enlargement of the male and female reproductive glands in Monarch butterflies.

The colleterial glands of female Monarch butterflies, and the accessory glands, tubular glands, and ejaculatory ducts of male Monarchs, exhibit considerable enlargement after eclosion in summer adults. Experiments using neck-ligatures and allatectomies, with or without injections of compounss with high juvenile hormone activity, show that the normal posteclosion hypertrophy of these organs is stimulated by juvenile hormone.     

Endocrine control of mucosal immunity in the female reproductive tract: impact of environmental disruptors

The complexity of the human female reproductive tract (FRT) with its multiple levels of hormonally controlled immune protection has only begun to be understood. Dissecting the functions and roles of the immune system in the FRT is complicated by the differential hormonal regulation of its distinct anatomical structures that vary throughout the menstrual cycle. Although many fundamental mechanisms of steroid regulation of reproductive tract immune function have been determined, the effects of exogenous synthetic steroids or endocrine disruptors on immune function and disease susceptibility in the FRT have yet to be evaluated in detail. There is increasing evidence that environmental or synthetic molecules can alter normal immune function. This review provides an overview of the innate and adaptive immune systems, the current status of immune function in the FRT and the potential risks of environmental or pharmacological molecules that may perturb this system.     

Endocrine characterization of female reproductive status in wild redfronted lemurs (Eulemur fulvus rufus)

In order to characterize the endocrine changes associated with ovarian function and pregnancy in wild redfronted lemurs (Eulemur fulvus rufus), profiles of immunoreactive 5alpha-pregnane-3alpha-ol-20-one (5-P-3OH) and total estrogens (E(t)) in feces were generated during the breeding season and gestation. HPLC data confirmed the presence of high amounts of 5-P-3OH in the feces of redfronted lemurs and showed that estrone and estradiol-17beta were the major estrogens excreted into feces, with estrone predominating. Due to an extreme day-to-day variability in excretion of both hormones during the breeding season, estrus cycle characterization was not possible for the free-ranging females. Comparison with endocrine data from captive animals suggested that this might have been associated with a highly variable amount of undigested fecal matter in the feces of wild females. A gestation length of 121.3 days was calculated on the basis of the day of behavioral estrus and date of parturition. Hormonally, pregnancy could be reliably diagnosed from day 40-45 after conception, when fecal progestogen levels clearly increased above breeding season concentrations in all females. Levels gradually increased thereafter, with 15- to 35-fold elevated maximum levels being reached shortly before parturition. In contrast, the pattern of fecal estrogen excretion was strongly related to the sex of the fetus in utero, with only females carrying male infants showing elevated (25- to 50-fold) estrogen levels during the last third of gestation, while levels remained at low breeding season levels in female-carrying mothers. Thus, fecal estrogen measurements during the last 6-7 weeks of gestation allow fetal sex to be determined prenatally. By providing the first data on the reproductive endocrinology of E. fulvus, we have shown that fecal hormone analysis is a useful tool to monitor endocrine changes associated with pregnancy, while it appears to have certain limitations regarding the assessment of ovarian function.     

Endocrine disorders & female infertility

Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.     

Impact of endocrine-disrupting compounds (EDCs) on female reproductive health

Evidence is accumulating that environmental chemicals (ECs) including endocrine-disrupting compounds (EDCs) can alter female reproductive development, fertility and onset of menopause. While not as clearly defined as in the male, this set of abnormalities may constitute an Ovarian Dysgenesis Syndrome with at least some origins of the syndrome arising during foetal development. ECs/EDCs have been shown to affect trophoblast and placental function, the female hypothalamo-pituitary-gonadal axis, onset of puberty and adult ovarian function. The effects of ECs/EDCs are complex, not least because it is emerging that low-level, 'real-life' mixtures of ECs/EDCs may carry significant biological potency. In addition, there is evidence that ECs/EDCs can alter the epigenome in a sexually dimorphic manner, which may lead to changes in the germ line and perhaps even to transgenerational effects. This review summarises the evidence for EC, including EDC, involvement in female reproductive dysfunction, it highlights potential mechanisms of EC action in the female and emphasises the need for further research into EC effects on female development and reproductive function.     

An epidemiological survey of female reproductive health status: gynecological complaints and sexually-transmitted diseases

An epidemiological survey of gynecological and sexually-transmitted diseases was conducted in 4 villages of Narmpong district, Khon Kaen, Thailand. It was focused on the reproductive health status of rural women. A mobile gynecological clinic was set up to collect materials and data including demographic characteristics, physical examination and specimen collection. Vaginal swabs were examined by microscope, Gram staining, pH measurement, KOH test and bacteriological cultivation. Endocervical swabs were examined for Chlamydia trachomatis, herpes simplex virus (HSV) and human papilloma virus (HPV) by polymerase chain reaction. Papanicolaou's test was applied for diagnosis of cytological abnormalities. Blood was tested by RPR and TPHA and urine was tested by LED test. The chief complaint was dysmenorrhea (44.8%). The others ranging from 43.4-3.0% were lower abdominal pain to genital ulcer. Prevalence of C. trachomatis, C. albicans, T. vaginalis, T. pallidum and G. vaginalis were found in 4.6, 10.9, 5.1, 2.7 and 1.0% of 586 women and HSV and HPV were found in 6.4% and 1.4% of 110 women, respectively. The three pathogens. C. trachomatis, C. albicans and T. vaginalis, were frequently found among women in the age of 20-49 years. The number of marriages and sex partners in the past year had an association with C. trachomatis infection while vaginal pH > 4.5, marital status, number of marriages and itching of genitalia had an association with T. vaginalis infection.     

甲状腺疾病对女性生殖功能的影响

甲状腺激素（TH）一方面直接作用于卵巢,另一方面通过影响性激素结合球蛋白（SHBG）的合成,调节泌乳素（PRL）、促性腺激素释放激素（GnRH）的分泌和凝血因子的功能而对月经周期进行调控。不孕女性的自身免疫性甲状腺疾病（AITD）患病率明显高于年龄匹配的经产妇,尤其是继发于子宫内膜异位或多囊卵巢综合征（PCOS）的不孕女性。伴或不伴AITD的妇女行辅助生殖技术（ART）的成功率并无显著差异。但患AITD的孕妇在妊娠前3个月发生流产的风险明显高于正常孕妇。此外,行ART之前的控制性超排卵（COH）过程对甲状腺功能有着不可忽略的影响,特别是对于合并AITD的妇女。故不孕妇女应于行ART之前筛查甲状腺功能,及时发现AITD,并在COH之后和妊娠期随访AITD妇女的甲状腺功能。妊娠早期阶段出现甲状腺功能异常的孕妇应接受L-Td治疗以避免妊娠并发症的发生。但关于是否应在孕前或孕期使用L—T。治疗甲状腺功能正常的AITD妇女仍缺乏足够的临床研究。     

Exercise-related female reproductive dysfunction.

Clinical or biochemical abnormalities of gonadal function, consisting of delayed puberty, luteal phase deficiency, oligo-amenorrhea or anovulation, occur in girls and women participating in strenuous sports. The evidence of a causal relationship between athletic activity and menstrual dysfunction has led to increased interest, also because the number of women who practice sports has increased rapidly. The pathogenesis of exercise-related female reproductive dysfunction (ERFRD) is not completely clarified. The heterogeneity of sports practice, the role of overtraining and other factors, as adequate calorie balance or the assumption of exogenous steroids, could play a primary role in the comprehension of the pathogenic mechanisms of reproductive dysfunction. The interest of physicians about ERFRD is also due to the consequences of reduced gonadal function on women's health. Apart from some short-term transient effects (i.e. on muscle, genito-urinary tract or behavior), hypoestrogenemia can induce long-term deleterious effects, as premature osteoporosis and lifelong impairment of skeletal structure. In view of the possible short-term (infertility) and long-term (osteoporosis) consequences of ERFRD, correct physical training and adequate diet approach are mandatory to prevent or to revert neuroendocrine abnormalities so frequently reported in girls and women participating in recreational or competitive athletic activities.     

Adipose tissue and reproductive health

The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the “satiety hormone” primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons. Meanwhile, adiponectin is notable for its action in mediating insulin sensitivity, with receptors found at every level of the reproductive axis. Both have been examined in the context of physiologic and pathologic reproductive conditions. Leptin has been shown to influence puberty, pregnancy, hypothalamic amenorrhea, and lipodystrophy, and with a potential therapeutic role for both metabolic and reproductive health. Adiponectin mediates the relative state of insulin resistance in pregnancy, and has been implicated in conditions such as polycystic ovary syndrome and reproductive malignancies. There are numerous other adipokines, including resistin, visfatin, chemerin and retinol binding protein-4, which may also play roles in reproductive health and disease states. The continued examination of these and other adipokines in both normal reproduction and reproductive pathologies represents an important avenue for continued study. Here, we seek to provide a broad, yet comprehensive overview of many facets of these relationships and highlight areas of consideration for clinicians and future study.     

Renin in the female reproductive system

Summary The female reproductive system is characterized by the presence of local renin-angiotensin systems within the evary and within the uterine lining. In the human ovary, renin arises from theca cells. In the uterus, the endometrium (uterine lining in the nonpregnant state) and the decidua (uterine lining in the pregnant state) are the major sources of renin. The primary form of renin produced by these extrarenal sources is prorenin. Angiotensin II, the active component of the renin cascade has a number of potential roles in the ovary and uterus. A key observation is that the human ovum and fetus is bathed in fluids rich in prorenin and angiotensin II.     

Neonatal handling and reproductive function in female rats

Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.