Another high priority topic for reproductive health is preconception care. This area has its roots in the Barker Hypothesis which states that adult diseases have their origins prior to birth. To this point, most experimentation has examined the relationship between adverse birth outcomes (e.g., low birth weight, intrauterine growth restriction, preeclampsia, pre-term birth, birth defects) and adult disease incidence as a result of perturbing the maternal-fetal environment. However, it is now clear from animal models that these adverse outcomes can occur during the embryonic period and even prior to implantation or conception itself (and can even be due to the paternal contribution). Thus, increased efforts are needed to define important developmental periods in which perturbations to normal physiological systems can result in poor pregnancy outcomes and to determine if these periods coincide with periods for important epigenetic modification of the genome. Because the sperm epigenome can be altered in response to various environmental factors, preconception care of the male is becoming increasingly important for the health of the offspring (and possibly later generations).
The Fertility and Infertility Branch (FIB) recognizes that the interactive needs of basic and clinical research necessary to address the above and related problems may be so complex that they cannot be solved by individual investigators working alone. Therefore, it is the intention of the FIB, contingent upon the availability of funds, to continue and maintain organized, multi-component reproduction and infertility research programs of high quality that focus on topics of high priority and significance that are critically important to the mission of the FIB, and that address important reproductive health concerns of the American public.
To address research gaps in the published BPA studies, in 2006, an organized committee sponsored by the National Institute of Environmental Health Sciences (NIEHS), National Institute of Dental Craniofacial Research (NIDCR), U.S. Environmental Protection Agency (EPA), and Commonweal reviewed the associations between BPA exposure and reproductive health outcomes and published their analyses in 2007 (). This committee was organized into five topic-driven panels that evaluated the available data and developed guidelines for the conduct of future in vivo and in vitro studies that would facilitate comparisons across studies and extrapolations to human health outcomes. Overall, the panels recommended the use of oral and dietary exposure routes, doses of BPA similar to human exposure levels, and further evaluations of BPA concentrations in animal and human tissues and fluids with the aim of using doses that would result in human-relevant serum concentrations of unconjugated BPA in studies with experimental animals.
A major objective of the NCTRI is to support specialized translational reproductive research programs of high quality, and to facilitate and accelerate bidirectional transfer of knowledge between the laboratory and clinic. This process of translating research between the laboratory and clinic is a continuum that encompasses all aspects of knowledge transfer from non-human animal models to humans. For example, application of information from rodent species to non-human primates is considered part of the translational continuum. However, the ultimate goal of supporting translational research through the NCTRI is to improve human reproductive health.
This FOA is specifically designed to stimulate the reproductive sciences research community to organize and maintain research-based centers of outstanding quality that, serving as national research resources, form a centers program that fosters communication, innovation and high quality reproduction and infertility research. To facilitate networking, investigators will have opportunities to participate in various Research Focus Groups (RFGs), comprised of investigators from other centers. Such networking will ensure that the reproductive research community remains in the forefront of the development and utilization of new technologies that can be used to diagnose, treat and ameliorate reproductive diseases and disorders, as well as to identify novel leads for fertility regulation.
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Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.
Between 2007 and 2013, new studies on the impact of BPA on the reproductive system have been conducted and are summarized in this review. Specifically, we focus on summarizing a) reproductive findings from human studies and how they compare with animal studies; b) detailed information about the experimental effects of BPA on a variety of reproductive end points, taking into account species, dose, route of exposure, and timing of exposure; and c) mechanisms of BPA action in the reproductive system, whenever possible. Thus, this update is a compilation of the more recent literature detailing the effects of BPA exposure on the female and male reproductive systems. We hope that the insights and conclusions of this review will be used to direct future studies and be used in developing consensus statements about the effects of BPA on the reproductive system based on the state of the evidence.
time, while sexually reproducing organisms are very successful in environments that change dramatically through time.
Animal Behavior: How does an animal’s behavior aid survival and reproduction? Provide an example to illustrate your comments. In your
Article strength determination. Similar to the 2007 expert panel, we considered the evidence to be strong when multiple studies in multiple species indicated a similar effect of BPA on a reproductive tissue or end point, even if concordance was not 100% across all studies, given that species and strain differences can lead to differences in dose response and magnitude of effect. We considered the evidence to be limited when some studies—but not the majority—indicated a similar effect of BPA on a reproductive tissue or end point, and/or when data from in vitro, in vivo animal, and human studies were discordant. Finally, we considered the evidence to be inconclusive when a limited number of studies had examined the effect of BPA on a selected reproductive tissue or end point, and/or when the studies were conducted in only one species or by in vitro studies alone. We recognize that in vitro studies have played critical roles in identifying how BPA affects specific tissues; however, because it is difficult to correlate human and animal health outcomes with in vitro outcomes alone, studies performed in vitro only were classified as inconclusive.
BPA exposure also appears to accelerate follicle transition and growth in several species. reported that neonatal BPA exposure accelerated follicle transition in lambs, decreasing numbers of primordial follicles and increasing primary follicles without affecting total follicle numbers. A similar enhanced activation of follicular recruitment was observed by in neonatally exposed Wistar rats. BPA exposure also increased cell proliferation, indicative of follicular growth, in small antral follicles in neonatally exposed lambs and Wistar rats (; ). Taken together, the data suggest that BPA enhances the recruitment and growth of primordial and primary follicles across species. Combined with the effects on germ cell nest breakdown, there is strong evidence that BPA induces ovotoxicity by acting on developing and immature follicle stages in animals models. However, the consequences of these effects on reproductive potential and longevity are unclear. In one study, low-dose neonatal BPA exposure decreased numbers of all follicle types and increased atretic follicles in rats during adulthood (). These effects of BPA on follicles could lead to premature reproductive senescence, but this needs to be confirmed in future studies.
Polycystic ovary syndrome (PCOS) is a major cause of female infertility, as well as of other reproductive system and other tissue and organ system morbidities. Identified more than 60 years ago, the etiology of PCOS still remains misunderstood. This insidious disease is currently the most common endocrine disorder of reproductive-aged women, affecting between five and 10 percent of women aged 15-44 or more than four million women in the U.S. Most, if not all, women with PCOS present with hyperandrogenemia, irregular menstrual cycles and polycystic ovaries. Often these conditions are accompanied by obesity and insulin resistance. Indeed, the risk of type 2 diabetes mellitus among PCOS patients is five- to 10-fold higher than in the normal population, and the prevalence of the Metabolic Syndrome is nearly two-fold higher in PCOS women than in the general population. Considering the high prevalence of diabetes in PCOS women, a very recent study estimated that the total annualized cost of evaluating and providing care to PCOS women is $4.6 billion dollars. However, the costs associated with endometriosis, PCOS and fibroids do not take into account that these women generally experience a lower quality of life due to the obesity, hirsutism, acne, and pain associated with these disorders.