The Impact of Age on the Female Reproductive System

Abstract

Evaluation of the female reproductive system in a general toxicity setting can be challenging for the toxicologic pathologist due to the cyclic nature of the estrous and menstrual cycles, timing of puberty and reproductive senescence, and species differences. Age in particular can have a significant impact on the histologic appearance of the female reproductive system and create challenges when trying to distinguish test article-related findings from normal developmental or senescent changes. This review describes the key physiologic and histologic features of immaturity, the transition through puberty, sexual maturity, and reproductive senescence in the female reproductive system, with an emphasis on practical applications for the toxicologic pathologist, and includes recommendations for distinguishing and documenting these developmental periods. Rats and cynomolgus monkeys are used as examples throughout with correlations to clinically observed end points to better aid the toxicologic pathologist in understanding how age may impact study interpretation.

Species Comparison of Postnatal Development of the Female Reproductive System

“…The presence of males can hasten the development in females. The onset of first estrus suggests hormonal cyclicity is established (Safranski et al, ), although the estrous cycles are typically irregular for some time before the attainment of regular estrous cycles (Goldman et al, ; Vidal, ; this study). This sequence is followed during normal puberty for mice and rats; however, there are minor shifts in the actual ages of these events for each species/strain.…”

“…In addition, it is common to see the uterus distended with fluid at this time, which would typically be consistent with “proestrus” in the classic 4‐day cycle descriptions, but often occurs here with vaginal keratinization (Vidal, ). It is important to recognize this poorly described microscopic pattern and not consider it to be a “mismatch” and diagnose an abnormality.…”

“…In mice, several days/weeks may pass after VO before a fully cornified smear is present, indicating first ovulation (Goldman et al, ). Histologically, ovulation can be indicated by the presence of corpus luteum in the ovary (Vidal, ). In the 7‐week‐old mouse (PND 35), 67% (4/6) of control C57BL/6J mice had CLs present (Li et al, ); however, there are variations in the timing in different strains of mice.…”

“…This was followed with a publication advising on the complications related to postnatal organ development that can be encountered in rat juvenile toxicity studies, specifically applicable are sections for brain and ovary (Picut and Parker, ). Additional information on the rat along with photomicrographs of pubertal changes can be found in Vidal () and Picut et al, (). Rehm et al (), Chandra and Adler (), and Chandra et al () provide beagle dog histologic atlas and hormone levels at different stages of the estrous cycle including mammary tissues with information on pubertal development.…”

Age Species of Women With Chronic Salpingoforitis

“…Заслуживает внимания тот факт, что возраст женщины определяет не только общесоматическое здоровье женщины, но и репродуктивный потенциал [5]. Более того, длительный воспалительный процесс отличается спектром возможностей провоцировать ДНК-индуцированную гибель клеток: от специфических повреждений ДНК до процессов вследствие повреждения ДНК и апоптоза [6].…”