Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary.

Polychlorinated biphenyls (PCBs) were used in industrial applications until they were banned in the 1970s, but they still persist in the environment. Little is known about the long-term effects of exposure to PCB mixtures on the rat ovary during critical developmental periods. Thus, this study tested whether prenatal and postnatal exposures to PCBs affect follicle numbers and gene expression in the ovaries of F1 offspring. Sprague-Dawley rats were treated with vehicle or Aroclor 1221 (A1221) at 1 mg/kg/day during embryonic days 8-18 and/or postnatal days (PND) 1-21. Ovaries from F1 rats were collected for assessment of follicle numbers and differential expression of estrogen receptor 1 (Esr1), estrogen receptor 2 (Esr2), androgen receptor (Ar), progesterone receptor (Pgr), and Ki-67 (Ki67) at PNDs 8, 32, and 60. Sera were collected for measurement of estradiol concentrations. Prenatal exposure to A1221 significantly decreased the number of primordial follicles and the total number of follicles at PND 32 compared to control. Postnatal PCB exposure borderline increased Ki67 gene expression and significantly increased Ki67 protein levels (PND 60) compared to control. Combined prenatal and postnatal PCB exposure borderline decreased Ar expression (PND 8) compared to control. However, PCB exposure did not significantly affect the expression of Pgr, Esr1, and Esr2 or serum estradiol concentrations compared to control at any time point. In conclusion, these data suggest that PCB exposure affects follicle numbers and levels of the proliferation marker Ki67, but it does not affect expression of some sex steroid hormone receptors in the rat ovary.

Pre- and postnatal developmental exposure to the polychlorinated biphenyl mixture aroclor 1221 alters female rat pituitary gonadotropins and estrogen receptor alpha levels.

Polychlorinated-biphenyls (PCBs) are industrial compounds, which were widely used in manufacturing of electrical parts and transformers. Despite being banned in 1979 due to human health concerns, they persist in the environment. In humans and experimental model systems, PCBs elicit toxicity in part by acting as endocrine-disrupting chemicals (EDCs). Aroclor 1221 (A1221) is a weakly estrogenic PCB mixture known to alter reproductive function in rodents. EDCs can impact hormone signaling at any level of the hypothalamic-pituitary-gonadal (HPG) axis, and we investigated the effects of A1221 exposure during the prenatal and postnatal developmental periods on pituitary hormone and steroid receptor expression in female rats. Examining offspring at 3 ages, postnatal day 8 (P8), P32 and P60, we found that prenatal exposure to A1221 increased P8 neonate pituitary luteinizing hormone beta (Lhb) mRNA and LHß gonadotrope cell number while decreasing LH serum hormone concentration. No changes in pituitary hormone or hormone receptor gene expression were observed peri-puberty at P32. In reproductively mature rats at P60, we found pituitary follicle stimulating hormone beta (Fshb) mRNA levels increased by prenatal A1221 exposure with no corresponding alterations in FSH hormone or FSHß expressing cell number. Estrogen receptor alpha (ERα) mRNA and protein levels were also increased at P60, but only following postnatal A1221 dosing. Together, these data illustrate that exposure to the PCB A1221, during critical developmental windows, alters pituitary gonadotropin hormone subunits and ERα levels in offspring at different phases of maturation, potentially impacting reproductive function in concert with other components of the HPG axis.

North-Central Florida Clinicians' Human Papillomavirus Vaccine Recommendation Priorities and Practices for 11- to 12-Year-Olds: A Discrete Choice Experiment.

PURPOSE: Within the United States, human papillomavirus (HPV) vaccination rates remain low. We examined HPV vaccine recommendation practices among Florida clinicians by assessing variability in: (1) recommendation priorities by patient characteristics and (2) concordance with best practices. METHODS: In 2018 and 2019, we conducted a cross-sectional survey incorporating a discrete choice experiment among primary care clinicians (MD/DO, APRN, and PA). We used linear mixed-effects models to determine the importance of patient characteristics (age, sex, time in practice, and chronic condition) and parental concerns. We compared clinician endorsement of predetermined constructs with reported vaccine recommendation statements. RESULTS: Among 540 surveys distributed, 272 were returned and 105 reported providing preventive care to 11- to 12-year-olds (43% response rate). Among completing clinicians, 21/99 (21%) did not offer the HPV vaccine. Among clinicians offering the vaccine (n = 78), 35%-37% of each decision to recommend the vaccine was based on the child's age (15 vs. 11 years). For closed-ended questions, most clinicians endorsed best practices including emphasizing cancer prevention (94% for girls and 85% for boys; p = .06), vaccine efficacy (60% both sexes), safety (58% girls and 56% boys), importance at 11-12 years (64% both sexes), and bundling vaccines (35% girls and 31% boys). When clinicians reported their typical recommendation, fewer clinicians incorporated best practices (59% cancer prevention, 5% safety, 8% the importance at 11-12 years, and 8% bundling vaccines). DISCUSSION: HPV vaccination recommendation strategies among Florida clinicians somewhat aligned with best practices. Alignment was higher when clinicians were explicitly asked to endorse constructs versus provide recommendations.

What Parents Should Know About Iron-Deficiency Anemia in Children.

This Patient Page describes how children may develop iron-deficiency anemia and provides information on how to make sure children have enough iron in their bodies.

What Parents Should Know About Sun and Sunburns in Children.

This Patient Page discusses how to prevent sunburns by avoiding midday sun exposure, using sunscreen, and wearing protective clothing.

A Pilot Test of a Workshop for Pediatric Clinicians About Communicating with Parents About the HPV Vaccine Using the C-LEAR Approach.

Low HPV vaccinations rates lead to missed opportunities to prevent cancer. Specifically, some parents (12-76%) report never receiving a recommendation for their child to receive the vaccine. Current models for talking about HPV vaccination fall short in that they focus primarily on how to introduce the vaccine with limited guidance on how to follow through with the conversation, particularly with those parents who may be hesitant. We developed the C-LEAR approach, an easy to remember, evidence-informed mnemonic to guide clinicians through the process of introducing and discussing the HPV vaccine with parents. We pilot tested this approach with a total of 20 pediatric clinicians (n = 13 residents; n = 7 attendings) in 60-min Zoom workshops that included a short didactic session, a demonstration of skills, and a small group, facilitator-led role play session. On an immediate post-training survey, all participants stated that the training was helpful and easy to understand. Ninety-four percent responded that they would implement what they had learned in their clinic. Participants reported appreciation for the small group sessions. While not specifically asked or required to incorporate the material into their practice, 1 year following the training, 8/9 (88%) participants reported using the C-LEAR approach in their clinics "most" or "all of the time." We are further testing this model through teaching our workshop in a large, randomized trial across the state of Florida.

Messaging preferences among Florida caregivers participating in focus groups who had not yet accepted the HPV vaccine for their 11- to 12-year-old child.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination rates remain low. The President's Cancer Panel suggests that effective messaging about the HPV vaccination focus on the vaccine's safety, efficacy, ability to prevent cancer, and recommendation at ages 11- to 12-years. We aimed to develop messages about HPV vaccine that include the President Cancer Panel's suggestions and were acceptable to caregivers of adolescents. METHODS: From August to October 2020, we conducted one-hour, Zoom videoconference focus groups with caregivers who lived in Florida, had an 11- to 12-year-old child, and had not had any of their children receive the HPV vaccine. Focus group moderators asked caregivers to react to three videos of clinician (i.e., MD, DO, APRN, PA) recommendations and three text message reminders. Thematic analysis was conducted using the constant comparative method and led by one author with qualitative analysis expertise. Two additional authors validated findings. RESULTS: Caregivers (n = 25 in six groups) were primarily non-Hispanic white (84%) and educated (64% had at least an Associate's degree). Approximately a third of caregivers had delayed (44%) or decided against a vaccine for their child (36%). Caregivers described six preferred message approaches: recognize caregivers' autonomy, balanced benefits and risks, trustworthy sources, increased feasibility of appointment scheduling, information prior to decision point, and preferred personalized information. Caregivers expressed a desire to have the follow-up doses mentioned in the introduction. CONCLUSIONS: HPV vaccine messages, whether delivered by a clinician or via text message, will be more acceptable to caregivers if they approach HPV vaccination as the caregivers' decision, and include information from trusted sources to help caregivers make an informed choice.

Effects of endocrine-disrupting chemicals on hypothalamic oxytocin and vasopressin systems.

Exposures to endocrine disrupting chemicals (EDCs) perturb hormonal systems. EDCs are particularly problematic when exposure happens in the fetus and infant due to the high sensitivity of developing organisms to hormone actions. Previous work has shown that prenatal polychlorinated biphenyl (PCB) exposure disrupts hypothalamic development, reproductive physiology, mate preference behavior, and social behaviors in a sexually dimorphic manner. Based on evidence that EDCs perturb social behaviors in rodents, we examined effects of PCBs on the neuropeptides oxytocin (OXT) and vasopressin (AVP) that are involved in regulating these behaviors. Rats were exposed prenatally (gestational days 16 and 18) to the weakly estrogenic PCB mixture Aroclor 1221 (0.5 or 1 mg/kg), to estradiol benzoate (EB, a positive control), or to the vehicle (3% dimethyl sulfoxide). In adult (~P90) brains, we counted immunolabeled oxytocin and vasopressin cell numbers in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. EDCs did not change absolute numbers of oxytocin or vasopressin cells in either region, although there were some modest shifts in the rostral-caudal distribution. Second, expression of genes for these nonapeptides (Oxt, Avp), their receptors (Oxtr, Avpr1a), and the estrogen receptor beta (Esr2), was determined by qPCR. In the PVN, there were dose-dependent effects of PCBs in males (Oxt, Oxtr), and effects of EB in females (Avp, Esr2). In the SON, Oxt, and Esr2 were affected by treatments in males. These changes to protein and gene expression caused by prenatal treatments suggest that transcriptional and posttranscriptional mechanisms play roles in mediating how EDCs reprogram hypothalamic development.

Human Papillomavirus Vaccination and Human Papillomavirus-Associated Cancer Rates Within Florida Counties.

INTRODUCTION: To direct interventions, the Florida counties with the greatest risk of current and future human papillomavirus‒associated cancers were identified by estimating county-level (1) percentages of adolescents aged 13-17 years who initiated (≥1 dose) and were up to date (2-3 doses) for the human papillomavirus vaccine and (2) human papillomavirus‒associated cancer incidence rates. METHODS: Records were obtained for human papillomavirus vaccinations from the Florida immunization registry (2006-2019), incident cancer cases from the Florida registry (2013-2017), and annual population counts from the Florida Department of Health (2006-2019). In 2020, annual county-level human papillomavirus vaccine initiation, human papillomavirus vaccine up-to-date, and age-adjusted human papillomavirus‒associated cancer incidence rates were estimated. RESULTS: Among adolescents aged 13-17 years, average 2018-2019 county-specific human papillomavirus vaccine initiation ranged from 38% to 100% for females and from 34% to 96% for males. Up-to-date estimates ranged from 20% to 72% for females and from 24% to 77% for males. The majority (78%) of counties with initiation and up-to-date estimates within the lowest tercile were located in Northern Florida. County-specific 2013-2017 annualized, adjusted human papillomavirus‒associated cancer incidence rates ranged from 0 to 29.8 per 100,000 among females and from 5.4 to 24.1 per 100,000 among males. Counties within the highest tercile for human papillomavirus‒associated cancers were primarily (90% for females and 77% for males) located in Northern Florida. CONCLUSIONS: Human papillomavirus‒associated cancer risk varies widely across Florida counties, with particularly high risk within Northern Florida. Targeting interventions toward counties with low vaccination and high cancer rates may reduce human papillomavirus‒associated cancers.

Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials.

BACKGROUND: There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PATIENTS AND METHODS: PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. RESULTS: Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). CONCLUSIONS: The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.

Heated tobacco product use among US adolescents in 2019: The new tobacco risk.

INTRODUCTION: There is growing public health concern about adolescent use of heated tobacco products (HTPs) after the US Food and Drug Administration approved the leading HTPs, IQOS, as a modified risk tobacco product. Extending the previous studies examining the correlates of HTP use among adolescents, this study aims to investigate potential risk factors for HTP use among US adolescents, including the use of multiple tobacco and flavored tobacco products. METHODS: We analyzed the 2019 National Youth Tobacco Survey (n=19018) and conducted a series of logistic regression models on awareness and use of HTPs as a function of tobacco use status (none, single, dual/poly) and past 30 days flavored tobacco use (e.g. menthol cigarette use, flavored e-cigarettes), controlling for sociodemographics. RESULTS: In multivariable analyses, awareness of HTPs was associated with usual menthol cigarette use (AOR=1.77; 95% CI: 1.23-2.53) and past 30 days flavored tobacco use (AOR=1.44; 95% CI: 1.16-1.80). Risk factors for ever HTP use included single (AOR=2.52; 95% CI: 1.19-5.33) and dual/poly tobacco use (AOR=4.94; 95% CI: 2.56-9.54), usual menthol cigarette use (AOR=2.50; 95% CI: 1.66-3.76), and past 30 days flavored tobacco use (AOR=1.61; 95% CI: 1.07-2.44). Risk factors for current HTP use included single (AOR=10.84; 95% CI: 6.72-17.49) and dual/poly tobacco use (AOR=31.96; 95% CI: 17.79-57.43), and usual menthol cigarette use (AOR=2.50; 95% CI: 1.63-3.85). CONCLUSIONS: This study documents HTP use in adolescents and contributes insight and urgency into prioritizing at-risk adolescents for interventions, including current users of other tobacco products and flavored tobacco users.

A feasibility trial of parent HPV vaccine reminders and phone-based motivational interviewing.

BACKGROUND: We assessed the feasibility and acceptability of a sequential approach of parent-targeted HPV vaccine reminders and phone-based Motivation Interviewing (MI). METHODS: In 2016, we selected all 11- to 12-year-old boys and girls seen in one clinic whose vaccine records did not include the HPV vaccine (n=286). By gender, we individually randomized parents of adolescents to an interactive text message (74 girls and 45 boys), postcard reminder (46 boys and no girls because of previously demonstrated efficacy), or standard care group (75 girls and 46 boys). Reminders were sent with medical director permission and a HIPAA waiver. Two months after reminders, among the adolescents whose vaccine records still did not include the HPV vaccine, we selected a gender-stratified random sample of 20 parents for phone-based MI. We assessed the percentage of deliverable messages, the percentage of parents' responding to the interactive text message, parent acceptability of receiving a text message, and MI parent responsiveness and interviewer competence (MI Treatment Integrity Coding system). RESULTS: Nearly all messages were deliverable (98% of postcards and 74% of text messages). Six of the 88 parents (7%) receiving text messages scheduled an appointment through our interactive system. The acceptability survey response rate was 37% (38/102). Respondents were favorable toward vaccine reminders for all parents (82%). Among 20 sampled parents, 17 were reached by phone of whom 7 completed MI, 4 had or were getting the HPV vaccine for their child, and 5 expressed disinterest. Across the 7 MI calls, the interviewer was rated 100% MI adherent and scored an average 4.19 rating for Global Spirit. CONCLUSION: Without providing explicit consent to receive vaccine-related messages, parents nonetheless found postcards and interactive text messages acceptable. Centralizing MI to phone calls with trained staff was acceptable to parents and resulted in highly MI-adherent interviews.

Transforming the Culture of Peer Review: Implementation Across Three Departments in an Academic Health Center.

OBJECTIVES: Although many health care institutions believe that clinical peer review is vital for identifying and improving quality of care, peer review is perceived by many clinicians as variable and inherently punitive. Successful peer review requires institutional leadership and adoption of a just culture approach to investigating and determining accountability for medical errors that result in harm. METHODS: We describe how an academic medical center implemented and adapted its clinical peer review processes to be consistent with just culture theory and provide a roadmap that other institutions may follow. Specific examples of peer review are highlighted to show how the process improved patient safety in the departments of emergency medicine, internal medicine, and pediatrics. RESULTS: The most significant process improvement was shifting from a tradition of assigning letter grades of "A," "B," or "C" to determine whether preventable adverse events were caused by "human error," "at-risk behavior," or "reckless behavior." This categorization of human behaviors enabled patient safety officers within 3 departments to develop specific interventions to protect patients and enlist physician support for improving clinical systems. CONCLUSIONS: Each department's success was due to recognition of different patient and provider cultures that offer unique challenges. The transformation of peer review was a crucial first step to shift perceptions of peer review from a punitive to a constructive process intended to improve patient safety. Our experience with reengineering clinical peer review shows the importance of focusing on just culture as a key method to prevent patient harm.

Postcard reminders for HPV vaccination mainly primed parents for providers' recommendations.

Parent-targeted reminders increase human papillomavirus (HPV) vaccination rates. Our postcard reminders increased HPV vaccine initiation (receipt of at least one dose) by 60% among girls, but not substantially among boys. To select a complementary intervention that would maximize the effect of reminders, we assessed the percentage increase in HPV vaccine initiation from reminders increasing preventive care visits or increasing the likelihood of vaccine receipt during preventive care. We conducted a secondary analysis of the postcard reminders from a quasi-experimental, factorial designed, feasibility trial conducted in 2013-2014 among 2,470 11- to 17-year-old girls enrolled in Florida's Medicaid or Children's Health Insurance Programs. We used log-linear models and a 4-way decomposition method to estimate the mediating and interacting effects of preventive visits on the effect of postcards on HPV vaccination. After receiving a preventive visit, 76% (269/356) of girls remained unvaccinated. Nearly half of the effect of postcards on HPV vaccination was mediated by preventive visits (44%; 95% CI = 9.2% to 78.0%). Postcards increased HPV vaccine initiation mainly by increasing the likelihood of HPV vaccine receipt during preventive visits (pure indirect effect = 32.3%; 95% CI = 1.5% to 63.1%), and also by increasing the occurrence of preventive visits (mediated interaction = 11.3%; 95% CI = 1.5 to 21.1). Reminders likely increased vaccination rates during well visits by priming parents for HPV vaccine conversations with their child's health care provider. Thus, reminder effectiveness may be increased if timed closely to preventive care visits and/or combined with interventions that improve provider recommendations. Trial Registration: ClinicalTrials.gov, NCT04208269, Registered 23, December 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04208269.

Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats.

Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.

Tobacco-Related Counseling and Documentation in Adolescent Primary Care Practice: Challenges and Opportunities.

INTRODUCTION: Primary care visits present an opportunity to reduce tobacco use and tobacco smoke exposure (TSE) among adolescents. To date, few studies have examined tobacco-related electronic health record (EHR) documentation in adolescent visits. The purpose of this study was to (1) describe tobacco-related EHR documentation practices in adolescent care clinics, including whether alternative tobacco products, parental use, and TSE were addressed; and (2) identify aspects of adolescent tobacco use that may inform EHR updates and counseling and documentation practices. METHODS: Following a convergent mixed-methods design, we conducted an EHR review of 508 adolescent well-child visits, performed focus groups with pediatric providers and staff, and conducted in-depth interviews with adolescent patients. Record review data and interview transcripts were analyzed and interpreted concurrently. RESULTS: In the EHR review, cigarette screening was documented in 92.3% of visits, smokeless tobacco screening in 51.4%, parental tobacco use in 23.2%, and home TSE in 33.1% of visits. Smoking status options were not mutually exclusive and did not include noncigarette products. No records documented assessment of e-cigarette use, despite nearly half of adolescent interview respondents citing these as the most popular products among adolescents. In interviews, adolescents discussed their experiences with alternative tobacco/nicotine products more than cigarettes. CONCLUSIONS: Tobacco use status prompts should be revised for clarity and include noncigarette tobacco products and TSE. Provider education on noncigarette products and TSE assessment is needed. Improvements in EHR systems, resources, and tools can lead to better tobacco screening, prevention, and treatment practices among primary care providers. IMPLICATIONS: Clinical guidelines call for pediatricians to assess and treat adolescent and parental tobacco use during primary care visits. The use of electronic health records (EHRs) can improve screening and counseling practices; however, few studies have examined tobacco-related EHR documentation practices in adolescent care settings. This mixed-methods study found low rates of EHR documentation related to noncigarette nicotine/tobacco products, parental tobacco use, and tobacco smoke exposure. These results demonstrate the need for increased provider training and EHR modifications to facilitate comprehensive tobacco control efforts in the adolescent population.

Endocrine-disrupting chemicals alter the neuromolecular phenotype in F2 generation adult male rats.

Endocrine-disrupting chemical (EDC) exposures to the fetus have long-lasting effects on health and disease in adulthood. Such EDC exposure to the F1 fetuses also reaches the germ cells that become the F2 generation. Previously, we demonstrated that adult social and communicative behaviors such as ultrasonic vocalizations and mating behaviors were altered by EDCs in F2 rats, especially males. In the current study, we used the brains of these F2 males to ascertain the underlying molecular changes in the hypothalamus related to these behavioral outcomes. Their progenitors were Sprague-Dawley rat dams, treated on pregnancy days 8 to 18 with one of three treatments: a polychlorinated biphenyl (PCB) mixture, Aroclor 1221, selected because it is weakly estrogenic; the anti-androgenic fungicide vinclozolin (VIN); or the vehicle, 6% dimethylsulfoxide in sesame oil (VEH). In adulthood, F1 male and female offspring were bred with untreated partners to generate paternal or maternal lineages of the F2 offspring, the subjects of molecular work. Quantitative real-time PCR was conducted in the medial preoptic area (POA) and the ventromedial nucleus (VMN) of the hypothalamus, selected for their roles in social and sexual behaviors. Of the genes assessed, steroid hormone receptors (estrogen receptor α, androgen receptor, progesterone receptor) but not dopamine receptors 1 and 2 or DNA methyltransferase 3a expression were altered, particularly in the VIN males. Several significant correlations between behavior and gene expression were also detected. These results suggest that preconceptional exposure of male rats to EDCs at the germ cell stage alters the neuromolecular phenotype in adulthood in a lineage-dependent manner.