Structural Sex Differences in the Mammalian Brain: Reconsidering the Male/Female Dichotomy
Akira Matsumoto in Sexual Differentiation of the Brain, 2017
To a limited extent, development of male-typical behavioral capacities occurs in the normal female rat as well. By the time of birth in the normal female, the brain appears to have been exposed to a limited yet influential level of steroid hormones, whether from the shared uterine environment or production by the female’s own endocrine glands.28-30 Anogenital distance, sexual behavior, and even the sexually dimorphic nucleus of the preoptic area (SDN-POA) volume appear to be influenced by the sex of a rat’s gestational neighbors.31 Thus it appears that in females of many species, partial androgenization of the brain may well underlie the well-documented occurrence of behavior traditionally categorized as male-typical, including mounting,32 intromission patterns,33 and ejaculation patterns,34 often reported to occur regardless of the presence of exogenous T. While a female-typical pattern of structure and behavior results from manipulations that remove or interfere with gonadal hormones in early development, we suggest that a semantic distinction should be maintained between the terms inherently female and indifferent or bipotential when describing the brain at various, rather arbitrary, developmental stages.
Testing for Reproductive Hazards from Dermal Exposure
Francis N. Marzulli, Howard I. Maibach in Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
Each litter should be examined on lactation day 0 as soon as possible after delivery to establish the number of live pups, the presence of gross anomalies, and the number of stillbirths. Pups found dead on day 0 should be examined to determine the cause of death. Each live pup should be counted, sexed, and weighed at birth (day 0), and on days 4, 7, 14, and 21 of lactation. The age of vaginal opening and preputial separation should be determined for F1 weanlings selected for mating. If there is a treatment-related effect in the F1 ratio or sexual maturation, anogenital distance should be measured on day 0 for all F2 pups.
The environment and reproduction
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
The correlation between animal experiments and human experience was nicely demonstrated by Swan et al. when they examined the relationship between neonatal anogenital distance (AGD), a sexually dimorphic feature considered to be a sensitive indicator of masculinization and phthalate metabolites (26). Phthalates (diesters of 1,2-benzenedicarboxylic acid) are a ubiquitous group of chemicals found in hundreds of products ranging from soft plastic vinyl toys and flooring to shampoos, soaps, and nail polish. High-molecular-weight phthalates are used in the manufacturing of flexible vinyl for flooring, wall coverings, food contact applications, and medical devices. Low-molecular-weight phthalates are used in personal care products as solvents and plasticizers for making lacquers, varnishes, and coatings used in pharmaceuticals for timed release drugs. Humans rapidly metabolize phthalate diesters (their half-lives are generally less than 24 hours), and thus do not accumulate them. Urinary biomarkers (phthalate monoesters), therefore, represent exposure in the last one to two days only. Swan et al. evaluated mother–son pairs who had been recruited for an unrelated pregnancy cohort study (n = 85) and found a significant inverse relationship between the level of phthalate metab-olites in the mother’s third-trimester urine and the son’s AGD at birth. Higher prenatal phthalate metabolite levels correlated with a shorter AGD, which, in turn, was associated with incomplete testicular descent and smaller penile volume. These findings demonstrate the effect an environmental chemical can have on morphological development. Although implied, further investigation is needed to comment specifically on fertility or fecundity.
Systematic review and quality ranking of studies of two phthalate metabolites and anogenital distance, bone health, inflammation, and oxidative stress
Published in Critical Reviews in Toxicology, 2019
Marina R. Sweeney, Keri G. O’Leary, Zsuzsanna Jeney, Megan C. Braunlin, Herman J. Gibb
A large number of reviews have been published on phthalates and various health outcomes in humans, including autism, reproductive systems, breast cancer, diabetes, and obesity (Goodman et al. 2014; Giulivo et al. 2016; Jeddi et al. 2016; Song et al. 2016). Anogenital distance (AGD), which is, generally, the distance between the anus and genitals, was most recently reviewed in 2014 (Kay et al. 2014). AGD is typically measured on infants, is longer for males, and has been studied in relation to testicular function and male fertility (Eisenberg and Lipshultz 2015). Several papers on AGD and phthalates have been published since 2014, warranting an updated review. Among the health outcomes for which data currently exist but that have not yet been reviewed are bone health, inflammation, and oxidative stress.
Anogenital distance and variability in semen parameters
Published in Systems Biology in Reproductive Medicine, 2018
José J. López-Espín, Consuelo Pérez-Palazón, Ana B. Maldonado-Cárceles, José D. Román-Arias, Jaime Mendiola, Alberto M. Torres-Cantero
Anogenital distance (AGD), the distance from the center of the anus to the genitals, is a sexually dimorphic phenotype in mammals being almost twice as long in males than females [Thankamony et al. 2009]. AGD has been recently associated to reproductive anomalies and male infertility [Eisenberg et al. 2011]. Studies in animals [Foster et al. 2001; Sharpe 2011] and human subjects [Mendiola et al. 2011; Eisenberg et al. 2012b; Dean and Sharpe 2013; Jain and Signal 2013; Thankamony et al. 2014] have shown that a shortened AGD was associated with cryptorchidism [Foster et al. 2001; Mendiola et al. 2011; Sharpe 2011; Eisenberg et al. 2012b; Dean and Sharpe 2013], hypospadias [Foster et al. 2001; Mendiola et al. 2011; Sharpe 2011; Eisenberg et al. 2012b; Hsieh et al. 2012; Dean and Sharpe 2013; Thankamony et al. 2014], lower serum testosterone levels [Foster et al. 2001; Mendiola et al. 2011; Dean and Sharpe 2013], decreased testis size [Dean and Sharpe 2013], lower penile length [Eisenberg et al. 2012a; Dean and Sharpe 2013; Thankamony et al. 2014], poor semen parameters [Eisenberg et al. 2011; Dean and Sharpe 2013; Mendiola et al. 2011], and non-obstructive azoospermia [Eisenberg et al. 2012b].
Prenatal stress decreases sperm quality, mature follicles and fertility in rats
Published in Systems Biology in Reproductive Medicine, 2019
Diana García-Vargas, Lizbeth Juárez-Rojas, Susana Rojas Maya, Socorro Retana-Márquez
The exposure of pregnant female rats to stressors during the critical period of brain sexual differentiation (gestation days 14–21) can cause intense and long-term postnatal effects in progeny reproduction (Segarra et al. 1991). This is known as prenatal programming of the neuroendocrine system regulating reproduction (Evans et al. 2016). In males, demasculinization and feminization of sexual behavior has been observed (Ward 1972; Weinstock 2001; Gerardin et al. 2005). The demasculinization of sexual behavior in prenatally stressed males is related to the attenuation of the testosterone peak at gestational days 18 and 19 (Ward et al. 2003). Prenatal stress is also correlated with reduced anogenital distance, a decrease in plasma LH, FSH and testosterone levels, as well as delayed testicular descent (Pallarés et al. 2013). Also, an increase in the percentage of TUNEL- and active caspase-3 positive cells (apoptotic index) in testis has been observed (Chen et al., 2013). Whether the alterations in testicular cells affect sperm quality and male fertility remain to be assessed in prenatally stressed males.
Related Knowledge Centers
- Dihydrotestosterone
- Endocrine Disruptor
- Phthalates
- Clitoris
- Scrotum
- Vagina
- Anus
- Sex Organ
- Sex Assignment
- Frenulum of Labia Minora