Species Comparison of Postnatal Development of the Female Reproductive System

Abstract

The postnatal development of the female reproductive system in laboratory animals and humans is reviewed. To enable a meaningful species comparison of the developing female reproductive system, common definitions of developmental processes were established with a focus made on aspects that are similar across species. A species comparison of the key endocrine, morphologic, and functional (onset of ovarian cycles and ability to reproduce) features of postnatal development of the female reproductive system is provided for human, nonhuman primate, dog, rat, and also mouse, minipig, and rabbit where possible. Species differences in the timing and control of female sexual maturation are highlighted. Additionally, a species comparison of the type and timing of female reproductive ovarian cycles was compiled. Human development provided the frame of reference, and then other common laboratory species were compared. The comparison has inherent challenges because the processes involved and sequence of events can differ greatly across species. Broad strokes were taken to assign a particular average age to an event and are to be used with caution. Methods of evaluation of postnatal female reproductive development in laboratory animals are discussed. Lastly, control rodent data from one of the author's laboratory on vaginal opening, first estrus, estrous cyclicity, and the histopathology involved with the developing female rat and mouse are presented. The information provided in this review is intended to be a resource for the design and interpretation of juvenile animal toxicity testing and ultimately, the relevance of the data to characterize potential risks for women and girls. Birth Defects Research 110:163-189, 2018. © 2017 Wiley Periodicals, Inc.

Adolescent rats show estrous cycle-mediated sex-differences in extinction of conditioned fear

“…The present study first showed that adolescent female Sprague-Dawley rats undergo puberty throughout P35-38, with 31% of P35 rats not having begun estrous cycling. This is consistent with previous research (Goldman, Laws, Balchak, Cooper, & Kavlock, 2000;Laffan et al, 2018). For adolescent females, the cycle was somewhat irregular (Figure 1c).…”

“…For adolescent females, the cycle was somewhat irregular (Figure 1c). This is also consistent with previous research reporting that for many mammalian species, including rats, the first few menstrual cycles are typically irregular (reviewed in Goldman et al, 2000;Laffan et al, 2018). Secondly, estrous phase during extinction significantly affected conditioned freezing in female adolescent rats.…”

“…Figure 1c shows the estrous stage for individual rats on each day. While estrous cycle is irregular for some of these animals, this is not unusual for first cycles following menarche (Laffan, Posobiec, Uhl, & Vidal, 2018).…”

Effects of early life stress on cocaine conditioning and AMPA receptor composition are sex-specific and driven by TNF

“…Thus, preference for a threshold-level drug-paired context may be driven by MSinduced TNF signaling specifically in males, since females show neither changes in TNF expression nor preference for a cocaine-paired chamber. While the female adolescents investigated here had not yet reached an age of sexual maturation and reliable ovarian cycling (Laffan et al, 2018), it remains possible that the sex-specific impact of MS on CPP was impacted by gonadal hormones. Since estradiol and progesterone have all been reported to influence drug-seeking behavior (e.g., (Lynch, 2008), it wil be important in future studies to determine the interactive effects of early life experience, sex hormones, and immune signals on CPP and other addiction-related behaviors.…”

Dose range finding approach for rodent preweaning juvenile animal studies

“…A second set of review articles (Ridings, 2018) was published which corroborates the recommendation that PND 4 in the rodent is generally similar to a term infant. Postnatal reviews were published on the eye (Van Cruchten et al, 2017), lung (Lewin & Hurtt, 2017), kidney (Frazier, 2017), male (Picut, Ziejewski, & Stanislaus, 2017) and female reproductive tracts (Laffan, Posobiec, Uhl, & Vidal, 2018), the gastrointestinal tract (Downes, 2018) and the ear (Powles‐Glover & Maconochie, 2018). There are also publications on the developing immune system (Holsapple, West, & Landreth, 2003; Kuper et al, 2016; Skaggs et al, 2019) and the CNS (Semple, Blomgren, Gimlin, Ferriero, & Noble‐Haeusslein, 2013; Wood, Beyer, & Cappon, 2003).…”