The Effects of Toxic Heavy Metals Lead, Cadmium and Copper on the Epidemiology of Male and Female Infertility.

Infertility is a major problem in modern society that affects a significant number of couples around the world. Heavy metals and a number of other factors have been causally linked to infertility. The aim of this study was to determine the effect of heavy metals lead, cadmium, and copper on the epidemiology of male and female infertility. Searches for articles published from 1982 to 2020 using related keywords such as male and female infertility and heavy metals were performed in scientific databases PubMed, Google Scholar, Science Direct, and others. The results showed that, in recent years, the number of infertile individuals has increased. Various environmental, occupational, and genetic factors have been described as potential causes. Heavy metals lead, cadmium, and copper cause infertility in couples through various mechanisms, such as changes in sperm motility factors, decreased semen quality, or effects on the egg. Exposure to physical phenomena such as radiation (ionized or microwave) and heat; stress and mental disorders; chemicals from cigarettes, respiratory pollutants (lead), insecticides and pesticides; anesthetic gases; and mercury and cytotoxic drugs may also contribute to the onset of infertility.

Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects.

Glyphosate base herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. Glyphosate, the active ingredient of all GBHs, is combined with other chemicals known as co-formulants that enhance the herbicide action. Nowadays, the safety of glyphosate and its formulations remain to be a controversial issue, as evidence is not conclusive whether the adverse effects are caused by GBH or glyphosate, and little is known about the contribution of co-formulants to the toxicity of herbicides. Currently, alarmingly increased levels of glyphosate have been detected in different environmental matrixes and in foodstuff, becoming an issue of social concern. Some in vitro and in vivo studies have shown that glyphosate and its formulations exhibit estrogen-like properties, and growing evidence has indicated they may disrupt normal endocrine function, with adverse consequences for reproductive health. Moreover, multigenerational effects have been reported and epigenetic mechanisms have been proved to be involved in the alterations induced by the herbicide. In this review, we provide an overview of: i) the routes and levels of human exposure to GBHs, ii) the potential estrogenic effects of glyphosate and GBHs in cell culture and animal models, iii) their long-term effects on female fertility and mechanisms of action, and iv) the consequences on health of successive generations.

Fertilidade e contracepção em mulheres com câncer em tratamento quimioterápico / Fertilidad y anticoncepción en mujeres con cáncer en tratamiento quimioterápico / Fertility and contraception in women with cancer treatment undergoing chemotherapy

RESUMO Objetivo identificar em mulheres em idade reprodutiva, com câncer e durante o tratamento quimioterápico, as orientações sobre preservação de fertilidade e planejamento reprodutivo e conhecer as informações fornecidas pela equipe de saúde. Métodos estudo descritivo, realizado com mulheres na pré-menopausa, com diagnóstico de câncer e em tratamento quimioterápico. A coleta de dados foi realizada com apoio de um instrumento com informações sociodemográficas, sobre o câncer e seus tratamentos, informações referentes a preservação de fertilidade e uso de métodos contraceptivos antes e após o diagnóstico do câncer. A análise dos dados foi feita por meio de estatística descritiva. Resultados a média de idade das 49 participantes foi de 38,2 anos (DP=6,1) e 79,6% estavam em tratamento devido ao câncer de mama. Quanto as informações recebidas sobre a importância do planejamento reprodutivo, 77,6% das participantes referiram que foram orientadas e 59,2% receberam tais orientações da equipe médica. Entretanto, em relação ao aconselhamento sobre métodos para manter a fertilidade, apenas, 6,1% das participantes foram orientadas. Conclusão e Implicações para a prática Deve-se considerar a relevância do aconselhamento especializado e a da manutenção de tomada de decisões ativas da mulher sobre a preservação de sua fertilidade.

RESUMEN Objetivo identificar en mujeres en edad reproductiva, con cáncer y durante el tratamiento de quimioterapia, las orientaciones sobre preservación de la fertilidad y planificación reproductiva y conocer las informaciones proporcionadas por el equipo de salud. Métodos estudio descriptivo, realizado con mujeres premenopáusicas diagnosticadas con cáncer y sometidas a quimioterapia. La recolección de datos se realizó con apoyo de un instrumento con información sociodemográfica sobre el cáncer y sus tratamientos, información sobre la preservación de la fertilidad y uso de métodos anticonceptivos antes y después del diagnóstico del cáncer. El análisis de los datos se realizó mediante estadística descriptiva. Resultados la media de edad fue de 38,2 años (DE= 6,1), y 79,6% estaban en tratamiento para el cáncer de mama. Cuanto a la información recibida sobre la importancia de la planificación reproductiva, 77,6% de los participantes informaron que estaban orientados y 59,2% recibió orientación del equipo médico. Sin embargo, con respecto al asesoramiento sobre métodos para mantener la fertilidad, solo 6,1% de las participantes recibieron asesoramiento. Conclusión e Implicaciones para la práctica Debe tenerse en cuenta la importancia de la asesoría experta y el mantenimiento de una toma de decisiones activa por parte de las mujeres para preservar su fertilidad.

ABSTRACT Objective to identify in women of reproductive age, with cancer and during chemotherapy treatment, the guidelines on fertility preservation and reproductive planning and to know the information provided by the health team. Methods descriptive study, conducted with premenopausal women diagnosed with cancer and undergoing chemotherapy. Data collection was performed with the support of an instrument with sociodemographic information about cancer and its treatments, information regarding the preservation of fertility and the use of contraceptive methods before and after cancer diagnosis. Data analysis was performed using descriptive statistics. Results the average age of the 49 participants was 38.2 years (SD=6.1) and 79.6% were being treated for breast cancer. Regarding the information received about the importance of reproductive planning, 77.6% of participants reported that they were oriented and 59.2% received such guidance from the medical team. However, regarding counseling on methods to maintain fertility, only 6.1% of participants were counseled. Conclusion and Implications for practice consideration should be given to the importance of expert counseling and the maintenance of active decision making by women about preserving their fertility.

Are glyphosate and glyphosate-based herbicides endocrine disruptors that alter female fertility?

Numerous evidences have alerted on the toxic effects of the exposure to glyphosate on living organisms. Glyphosate is the herbicide most used in crops such as maize and soybean worldwide, which implies that several non-target species are at a high risk of exposure. Although the Environmental Protection Agency (EPA-USA) has reaffirmed that glyphosate is safe for users, there are controversial studies that question this statement. Some of the reported effects are due to exposure to high doses; however, recent evidences have shown that exposure to low doses could also alter the development of the female reproductive tract, with consequences on fertility. Different animal models of exposure to glyphosate or glyphosate-based herbicides (GBHs) have shown that the effects on the female reproductive tract may be related to the potential and/or mechanisms of actions of an endocrine-disrupting compound. Studies have also demonstrated that the exposure to GBHs alters the development and differentiation of ovarian follicles and uterus, affecting fertility when animals are exposed before puberty. In addition, exposure to GBHs during gestation could alter the development of the offspring (F1 and F2). The main mechanism described associated with the endocrine-disrupting effect of GBHs is the modulation of estrogen receptors and molecules involved in the estrogenic pathways. This review summarizes the endocrine-disrupting effects of exposure to glyphosate and GBHs at low or "environmentally relevant" doses in the female reproductive tissues. Data suggesting that, at low doses, GBHs may have adverse effects on the female reproductive tract fertility are discussed.

Fertility concerns among breast cancer patients in Mexico.

OBJECTIVE: Young women represent a high proportion of the total number of breast cancer (BC) patients in Mexico; however, no previous studies addressing their attitudes regarding the risk of chemotherapy-induced infertility and its contributing factors are available. The aim of this study was to evaluate the concerns of young women with BC towards the risk of infertility in two referral centers in Mexico with access to public health services. METHODS: A cross-sectional study including women with newly or previously detected BC aged 40 years or younger at diagnosis was conducted. Variables regarding concerns about fertility were collected from an adapted version of the Fertility Issues Survey. RESULTS: 134 consecutive eligible women responded to the in-person paper survey. 55% were partnered, 35.1% had no children, and 48% reported willingness to have children prior to BC diagnosis. Only 3% of patients considered to be able to afford extra expenses. At diagnosis, 44% of women expressed some level of concern about infertility risk. The only factor significantly associated with fertility concern was the desire of having children prior to diagnosis (OR 11.83, p = 0.006). Only 30.6% patients recalled having received information regarding infertility risk from their physicians. CONCLUSION: A minority of young women with breast cancer in Mexico is informed about the risk of BC treatment-induced infertility, despite substantial interest. Informing all patients about infertility risk and available options for fertility preservation should be an essential aspect of the supportive care of young women with BC, even in low-middle income countries such as Mexico.

Gonadotropin-Releasing Hormone Agonists for Ovarian Function Preservation in Premenopausal Women Undergoing Chemotherapy for Early-Stage Breast Cancer: A Systematic Review and Meta-analysis.

IMPORTANCE: Chemotherapy may result in a detrimental effect on ovarian function and fertility in premenopausal women undergoing treatment for early-stage breast cancer (EBC). To minimize risk of harm to ovarian function and fertility for patients in this setting, careful considerations should be made. Gonadotropin-releasing hormone agonists (GnRHa) have been suggested as an alternative to prevent the loss of ovarian function due to exposure to cytotoxic agents, but GnRHa use for ovarian protection in EBC patients is not fully resolved. OBJECTIVE: To determine the effectiveness of GnRHa administered concurrently with chemotherapy for ovarian function preservation. DATA SOURCES: PubMed, SCOPUS, and Cochrane databases were searched for studies published between January 1975 and March 2015. The abstracts of the American Society of Clinical Oncology Annual Meeting between 1995 and 2014 and the San Antonio Breast Cancer Symposium between 2009 and 2014 were searched as well. STUDY SELECTION: Prospective, randomized, clinical trials addressing the role of ovarian suppression with GnRHa in preventing early ovarian dysfunction in premenopausal women undergoing treatment for EBC were selected. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed independently by 2 authors. The methodology and the risk of bias were assessment based on the description of randomization method, withdrawals, and blinding process. MAIN OUTCOMES AND MEASURES: Rate of resumption of regular menses after a minimal follow-up period of 6 months following chemotherapy was used as a surrogate to assess the incidence of ovarian dysfunction. Additional secondary outcomes included hormone levels and number of pregnancies. Risk ratio estimates were calculated based on the number of evaluable patients. Analyses were conducted using a random effect model. RESULTS: Seven studies were included in this analysis, totaling 1047 randomized patients and 856 evaluable patients. The use of GnRHa was associated with a higher rate of recovery of regular menses after 6 months (odds ratio [OR], 2.41; 95% CI, 1.40-4.15; P = .002) and at least 12 months (OR, 1.85; 95% CI, 1.33-2.59; P < .001) following the last chemotherapy cycle. The use of GnRHa was also associated with a higher number of pregnancies (OR, 1.85; 95% CI, 1.02-3.36; P = .04), although this outcome was not uniformly reported and fertility or rate of pregnancy was not the primary outcome in any of the trials. CONCLUSIONS AND RELEVANCE: Gonadotropin-releasing hormone agonists given with chemotherapy was associated with increased rates of recovery of regular menses in this meta-analysis. Evidence was insufficient to assess outcomes related to GnRHa and ovarian function and fertility and needs further investigation.

Repercussões do tratamento quimioterápico sobre a função ovariana / Repercussions of chemotherapy on ovarian function

Os tratamentos quimioterápicos atuais têm aumentado bastante a sobrevida de pacientes acometidas por diversos tipos de câncer; porém, podem causar falência ovariana e infertilidade. É importante o médico estar atento aos riscos de ocorrência dessas sequelas para tentar preservar a qualidade de vida das pacientes. Este artigo apresenta uma revisão acerca de recursos propedêuticos que podem ser utilizados na avaliação da função ovariana e de dados sobre a possível disfunção ovariana pós-quimioterapia. Normalmente essa disfunção não ocorre imediatamente após o tratamento, manifestando-se mais tarde como menopausa precoce. Procedimentos podem ser realizados com o intuito de se preservar a fertilidade e/ou a função ovariana.

New chemotherapic treatment have been raising the lifetime of the patients with cancer. However, important sequelas of these treatments, as ovary failure and infertility, may occur. It is important to the doctor to be aware of the risks of these side effects occurrence in order to maintain the quality of life for those patients. This article presents a review about the propedeutic resources that can be used to analyze the ovarian function and important data about the possible ovary dysfunction after chemotherapy. In most patients the ovary dysfunction will not occur immediately after the treatment expressing later as an early menopause scene. Some procedures can be performed in order to try to preserve the fertility and the ovary function.

Organochlorine compound levels in fertile and infertile women from Rio de Janeiro, Brazil.

OBJECTIVE: The aim of the study was quantify organochlorine compounds in women seeking for infertility treatment (n = 15) and in spontaneously pregnant ones (n = 21). MATERIALS AND METHODS: A questionnaire was applied regarding lifestyle, occupational and reproductive history. Blood samples were collected from both groups. RESULTS: From the pesticides studied, pp'DDE was detected in 100% of infertile women, at higher mean levels than in pregnant women (3.02 mcg/L vs. 0.88 mcg/L; p = 0.001; power of 69%), without correlation with the etiology of infertility. Levels of the polychlorinated biphenyls (PCBs) were low, with positive samples in 100% in the infertile women for PCBs 138, 153, 180, while in pregnant women, they were 85.7% for congeners 138 and 153. Only PCB180 showed significance, with frequency of 71.4% (p = 0.019). CONCLUSIONS: The risk factors for female infertility were: age, consumption of untreated water and of canned foods. Exposure to the most prevalent organochlorine compounds described in literature was confirmed in the study, indicating that pp'DDE may adversely influence female fertility.

Organochlorine compound levels in fertile and infertile women from Rio de Janeiro, Brazil / Níveis de substâncias organocloradas em mulheres férteis e inférteis do Rio de Janeiro, Brasil

OBJECTIVE: The aim of the study was quantify organochlorine compounds in women seeking for infertility treatment (n = 15) and in spontaneously pregnant ones (n = 21). MATERIALS AND METHODS: A questionnaire was applied regarding lifestyle, occupational and reproductive history. Blood samples were collected from both groups. RESULTS: From the pesticides studied, pp'DDE was detected in 100% of infertile women, at higher mean levels than in pregnant women (3.02 mcg/L vs. 0.88 mcg/L; p = 0.001; power of 69%), without correlation with the etiology of infertility. Levels of the polychlorinated biphenyls (PCBs) were low, with positive samples in 100% in the infertile women for PCBs 138, 153, 180, while in pregnant women, they were 85.7% for congeners 138 and 153. Only PCB180 showed significance, with frequency of 71.4% (p = 0.019). CONCLUSIONS: The risk factors for female infertility were: age, consumption of untreated water and of canned foods. Exposure to the most prevalent organochlorine compounds described in literature was confirmed in the study, indicating that pp'DDE may adversely influence female fertility.

OBJETIVO: O estudo teve como objetivo quantificar as substâncias organocloradas em mulheres buscando tratamento para infertilidade (n = 15) e que espontaneamente engravidaram (n = 21). MATERIAIS E MÉTODOS: Foi aplicado questionário considerando estilo de vida, história ocupacional e reprodutiva. Amostras de sangue foram obtidas em ambos os grupos. RESULTADOS: Dos pesticidas, pp'DDE foi detectado em 100% das inférteis, com níveis maiores que nas grávidas (3,02 mcg/L vs. 0,88 mcg/L; p = 0,001; poder 69%), sem correlação na etiologia da infertilidade. Os níveis de detecção das bifenilas policloradas (PCBs) foram baixos, com 100% de positividade das amostras nas inférteis para os PCBs 138, 153, 180, e de 85,7% nas grávidas para os congêneres 138 e 153. Apenas PCB180 mostrou significância na frequência de 71,4% (p = 0,019). CONCLUSÕES: Os fatores de risco para infertilidade feminina foram: idade, consumo de água não tratada e alimentos enlatados. A exposição aos organoclorados mais prevalentes descritos na literatura foi confirmada no estudo, indicando que pp'DDE pode influenciar adversamente a fertilidade feminina.

Organotins: a review of their reproductive toxicity, biochemistry, and environmental fate.

The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to organotins. Organotins are pollutants that are used as biocides in antifouling paints. They produce endocrine-disrupting effects in mollusks, such as imposex. In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen. The adverse effects that appear in rodents have raised concerns about organotins' potential health risk to humans in relation to organotin exposure. At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity. For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta. With these risks in mind, it is important to improve our knowledge of organotins' effects on environmental health.

Depot GnRH-agonist trigger for breast-cancer patient undergoing ovarian stimulation resulted in mature oocytes for cryopreservation: a case report.

This report describes the case of a 27-year-old woman with breast cancer who underwent ovarian stimulation for fertility preservation with recombinant FSH in conjunction with a gonadotrophin-releasing hormone (GnRH) antagonist and an aromatase inhibitor from the beginning of the treatment. A 3.75-mg triptorelin depot formulation was given intramuscularly when the follicular diameter of three follicles reached ≥ 20 mm and a total of 13 follicles reached ≥ 15 mm. Oocyte retrieval was scheduled for 36 h later and 10 mature oocytes were collected and vitrified. This case report demonstrates that a depot GnRH-agonist trigger effectively leads to mature oocyte retrieval, with the advantage of initiating ovarian suppression for the purpose of fertility preservation during adjuvant chemotherapy in breast-cancer patients.

[Breast cancer and subsequent pregnancy. Infertility, death risk and survival]. / Cáncer de mama y embarazo subsiguiente. Infertilidad, riesgo de muerte y supervivencia.

BACKGROUND: The chemotherapy commonly used for the treatment of breast cancer affect the fertility and could cause premature ovarian failure. The subsequent pregnancy to the breast cancer therefore it is not habitual. OBJECTIVE: The purpose of this study was to identify the effects of the chemotherapy in the women reproductive life; to evaluate the frequency of the women that experienced a later pregnancy after treatment of cancer, as well as the effects of the subsequent pregnancy on the breast cancer. We report our experience in the 14 year period. MATERIAL AND METHOD: As retrospective design, of 14 cases with breast cancer and subsequent pregnancy, from March 1994 to June 2008; demographic variables, clinical presentation, histopathological data, diagnostic procedures, treatments and results of the pregnancy were identified. RESULTS: The mean (M +/- SD) age of gestational women was of 31.5 +/- 5.2 years; the 83.3% women received adyuvant chemotherapy with antraciclines; the patients with regional illness (> 4 N+) and advanced illness had an adverse presage; the systemic relapse and progression showed in 42.8% of the cases. The pregnancy to term was presented in half of the cases in the first two years and in a third part, later to the 2 years of having concluded the oncological treatment; of the fourteen patients with breast cancer presented a total of 16 pregnancies: 9 were of term, 3 of preterm and 4 abortions. CONCLUSIONS: The study founds are based on a series of cases, which do not suggest that the pregnancy after the diagnosis and treatment of breast cancer has some adverse effect in the patients survival, for what the patients can conceive later to the oncological treatment. However, in this study it was observed that the effect of the advanced stage and positive axillary ganglion (> 4) influence in the relapses.

Postnatal development and fertility of offspring from mice exposed to triphenyltin (fentin) hydroxide during pregnancy and lactation.

Fentin or triphenylthin (TPT) is an organotin compound (OTC) widely used as an agricultural fungicide and miticide. It is well known that TPT exerts adverse effects on the reproductive and immune systems and may disrupt the endocrine system, raising concerns regarding the risks posed by exposure to this metal on environmental and human health. In this study the effects of maternal exposure to TPT at doses of control (0), 1.875, 3.75, or 7.5 mg/kg body weight/d, po, were examined during gestation and lactation on offspring growth, organ weights, and fertility. Except for a significant liver enlargement at the highest dose, TPT produced no maternal toxicity. Increased neonatal mortality (death of 3 entire litters from a total of 18 treated litters) was noted at 7.5 mg/kg. Pup body weight at birth was significantly reduced at all dose levels, but no marked weight loss was found on postnatal day (PND) 5 and thereafter. Offspring maturation (ear unfolding, incisor eruption, vagina opening, and testes descent) and fertility in adulthood were not significantly affected by maternal exposure to TPT. In conclusion, data provided by this study indicate that maternal treatment with TPT during pregnancy and lactation delayed prenatal growth but did not impair postnatal development and fertility in exposed offspring in adulthood.

Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide.

BACKGROUND: Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy. METHODS: Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n=9) received placebo twice; group II (n=12) received placebo+cyclophosphamide (CPA); group III (n=12) received GnRHant+CPA; and group IV (n=9) received GnRHant+placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted. RESULTS: Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p<0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00+/-1.33 pups vs. group I, 11.44+/-0.78 pups, p<0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00+/-1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1+/-1.22 vs. 10.9+/-0.70, p<0.05). CONCLUSION: The use of a GnRHant before CPA chemotherapy provided protection of fertility.

Reproductive toxicity of phthalate esters.

Phthalate esters are ubiquitous environmental contaminants that in general display low-toxicity. Overall, the reproductive effects of these compounds are well characterized in adult's animals, with gonadal injury observed after high dose exposure. However, results of recent transgeneration studies indicate that the reproductive system of developing animals is particularly vulnerable to certain phthalates. The phenotypic alterations observed in male offspring rats exposed during the perinatal period have remarkable similarities with common human reproductive disorders, including cryptorchidism, hypospadias and low-sperm counts. Recent results also indicate that high phthalate doses can adversely affect adult and developing female rats. However, the main question involving phthalates is whether the current level of human exposure is sufficient to adversely affect male and/or female reproductive health. Here, we review the reproductive toxicity data of phthalates in adult and developing animals as well as possible modes of action. In addition, we briefly discuss the relevance of animal studies to humans in light of recent epidemiological data and experimental research with low (human relevant) doses. Finally, we point out some critical issues that should be addressed in order to clarify the implications of phthalates for human reproduction.

Fertility preservation in women with breast cancer undergoing adjuvant chemotherapy: a systematic review.

OBJECTIVE: To investigate methods of fertility preservation in younger women exposed to adjuvant chemotherapy for breast cancer. DESIGN: Systematic review of literature. SETTING: Academic Department of Medical Oncology. PATIENT(S): Premenopausal women exposed to adjuvant chemotherapy for breast cancer. MAIN OUTCOME MEASURE(S): Fertility preservation. RESULT(S): Data for fertility preservation in this setting come from nonrandomized trials and observational studies. The main methods of fertility preservation are ovarian protection by gonadotropin-releasing hormone (GnRH) agonists, cryopreservation of embryos after in vitro fertilization, and preservation of operatively sampled ovarian tissue or eggs after stimulation and puncture. Ongoing trials are assessing the role of ovarian protection by GnRH agonists. CONCLUSION(S): At present, there are no high-level, evidence-based recommendations for preservation of fertility or of ovarian function in women with breast cancer. This is an important issue for young breast cancer survivors, and further studies are needed. Moreover, the interplay between ovarian protection by GnRH agonists and the efficacy of adjuvant chemotherapy remains elusive.

Decreased fertility in mice exposed to environmental air pollution in the city of Sao Paulo.

It has largely been shown that air pollution can affect human health. Effects on human fertility have been shown mainly in males by a decrease in semen quality. Few studies have focused on the environmental effects on female fertility. The aim of the present study was to analyze the effects of air pollution in the city of Sao Paulo on mouse female fertility. Four groups of female Balb/c mice were placed in two chambers 10 days (newborn) or 10 weeks (adults) after birth. Mice were maintained in the chambers 24 h a day, 7 days a week, for 4 months. The first chamber received air that had passed through an air filter (clean chamber) and the second received ambient air (polluted chamber). We measured PM10 and NO2 inside both chambers. Mice belonging to the adult groups were bred to male mice after living for 3 months inside the chambers. The newborn groups mated after reaching reproductive age (12 weeks). After 19 days of pregnancy the numbers of live-born pups, reabsorptions, fetal deaths, corpora lutea, and implantation failures were determined. PM10 and NO2 concentrations in the clean chamber were 50% and 77.5% lower than in the polluted chamber, respectively. Differences in fertility parameters between groups were observed only in animals exposed to air pollution at an early age (10 days after birth). We observed a higher number of live-born pups per animal in the clean chamber than per animal from the polluted chamber (median=6.0 and 4.0, respectively; P=0.037). There was a higher incidence of implantation failures in the polluted group than in the clean group (median=3.5 and 2.0, respectively; P=0.048). There were no significant differences in the other reproductive parameters between groups. These results support the concept that female reproductive health represents a target of air pollutants.

Reproductive aspects in female rats exposed prenatally to hydrocortisone.

We investigated the effects of hydrocortisone during the prenatal period and its later repercussion on reproductive aspects of female rats. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of pregnancy. Although the present study was not intended to identify mechanisms of toxicity, the treatment with hydrocortisone in the last period of pregnancy presented no signs of toxicity. The efficacy of the hydrocortisone in reducing the adrenal wet mass and plasma corticosterone levels immediately after delivery in both the treated mothers and in respective pups at birth may indicate impairment of the hypothalamus-pituitary-adrenal axis. In addition, the treatment with hydrocortisone did not interfere in the development of the female descendants until puberty. However, it affected the estrous cycle and fertility. Probably, the prenatal exposure to corticosteroids had altered at least partially the hypothalamus-pituitary-gonadal axis, resulting in the damages observed in adult life. These results indicate that the use of the hydrocortisone at a dose that apparently does not endanger the neonate led to undesirable effects in the adult reproductive phase, resulting in later deleterious alteration of the reproductive physiology in female rats.

[Time to pregnancy and lead exposure]. / Exposición al plomo y su relación con el tiempo requerido para embarazo.

OBJECTIVE: To determine the effects of lead exposure on the time elapsed to become pregnant. MATERIAL AND METHODS: The study population consisted of 142 women residing in Mexico City between 1997 and 2001, who were already participating in a study to evaluate effects of lead exposure on reproductive health. Measurements of lead in bone were performed when women were first admitted to the program. Information on lead exposure and other variables of interest was obtained through a questionnaire. Participants were followed up to assess the relationship between the time required to become pregnant and lead exposure. Statistical analysis consisted of Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Of the total number of women in the program, 42 got pregnant: 34 before the first year of follow-up, and 8 at a later date. The mean value for lead concentration in blood was 9.3 micrograms/dl. The mean values for lead concentration in patella and tibia were 16.0 y 11.0 micrograms Pb/g of bone, respectively. Survival analysis was performed and no differences were detected in blood lead levels and time to pregnancy in the first year. Nevertheless, in women with blood lead levels above 10.0 micrograms/dl, the likelihood of not achieving pregnancy was five times higher (95% confidence interval [CI] 0.05-0.56) after one year of follow-up compared with women with blood lead levels below 10.0 micrograms/dl. CONCLUSIONS: Exposure to high lead concentrations may be an important risk factor influencing the time period for a woman to get pregnant, especially in fertile women who have tried to get pregnant for more than a year. This paper is available too at: http://www.insp.mx/salud/index.html.