Developmental Changes in Human Fetal Testicular Cell Numbers and Messenger Ribonucleic Acid Levels during the Second Trimester

Abstract

Context:Normal fetal testis development is essential for masculinization and subsequent adult fertility. The second trimester is a critical period of human testicular development and masculinization, but there is a paucity of reliable developmental data.Objective: The objective of the study was to analyze second-trimester human testicular morphology and function.Design: This was an observational study of second-trimester testis development. Setting:The study was conducted at the Universities of Glasgow and Aberdeen.Patients/Participants: Testes were collected from 57 morphologically normal fetuses of women undergoing elective termination of normally progressing pregnancies (11-19 wk gestation).Main Outcome Measure(s): Testicular morphology, cell numbers, and quantitative expression of 22 key testicular genes were determined.

Ontogenesis of testicular function in humans.

“…Sertoli cells proliferate in seminiferous cords, and we have shown in vitro that their rate of proliferation is about 2-3%, and less than 1% of the cells are apoptotic. These data are in accordance with the studies of Bendsen and O'Shaughnessy indicating that Sertoli cells increase regularly in number during the first and second trimesters of gestation [3,4].…”

“…These data are in accordance with the studies of Bendsen and O'Shaughnessy indicating that germ cells increase regularly in number during the first and second trimesters of gestation [3,4]. In rodents, the gonocytes proliferate in the seminiferous cords until fetal day 18.5 (rat) or 15.5 (mouse), after which they become quiescent until postnatal day 2- 3 (rat) or birth (mouse), when they resume mitosis (Fig.…”

A comparison between D2-40 and c-KIT immunohistochemistry for the human fetal testis and ovary at the second trimester of gestation

“…Likewise, according to Pauls et al 9) , nearly all male germ cells with the morphological features of gonocytes and intermediate cells coexpressed c-KIT and M2A: starting from week 2 of gestation, their number increased up to week 8/9 and then declined continuously during further development until, after week 25, prespermatogonia were predominant and did not express these markers, possibly because their pluripotency had been lost. Similar findings were reported by O'Shaughnessy et al 0) on the basis of observations of -9-week male fetuses, although they did not use M2A as a marker. In spite of the frequent application of M2A or c-KIT for fetal studies, there have been few attempts to compare the two markers 8,9) (for details see Discussion).…”

Mutations of CXorf6 are associated with a range of severities of hypospadias

“…Because defective testicular androgen production or responsiveness is known to lead to hypospadias, CXorf6 was first suspected to impair the production of androgen. Previous studies indicated that CXorf6 is expressed in fetal Sertoli and Leydig cells during the critical period for sex development (12,20). Moreover, CXorf6 augments testosterone production and contains the steroidogenic factor 1 (SF1) target sequence (21).…”