Study Origin of Germ Cells and Formation of New Primary Follicles in Adult Human and Rat Ovaries

Abstract

The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

“…Folliculogenesis in the adult ovary is characterized by extensive architectural remodeling that culminates in disruption of the coelomic epithelium and extrusion of the ovum at ovulation (1,2). After disruption, a series of molecular events initiates and executes repair of the epithelial wound (3,4).…”

Reproductive ageing in women

“…In a later paper, the same group modified their view and suggested that bone marrow-derived germinal stem cells are distributed by peripheral blood to the mouse ovaries [203]. Another group provided evidence for the in vivo de novo differentiation of mesenchymal progenitor cells residing in the ovarian tunica albuginea into primitive granulosa and germ cells in the adult human female [204]. The same group also demonstrated the in vitro differentiation of cells derived from adult human ovarian surface epithelium into oocytes and granulosa cells [205].…”

Applicability of adult techniques for ovarian preservation to childhood cancer patients

“…This approach, possibly with the exception of transplant to the pelvic peritoneum, requires performing in vitro fertilization for fertility purposes. Nevertheless, there have been reports of spontaneous pregnancies after heterotopic transplantation to the subcutaneous and intramuscular tissues, possibly due to reintroduction of ovarian germinal cells with the tissue transplant [10,64]. Based on this hypothesis, germinal stem cells contained in the transplanted tissue would re-colonize the ovary/ies or would trigger the existing quiescent germinal stem cells to develop into follicles and oocytes capable of producing pregnancies.…”

“…It has been a dogmatic belief that follicle reserve is established in utero in humans, and that there is no regeneration postnatally [9]. However, recent studies claimed 'regeneration' of new follicles from stem cells in adult human ovaries [10]. In support of this new notion is the observation that many women conceive years after experiencing premature menopause as a result of high-dose chemotherapy and or radiotherapy [11,12], or even after idiopathic primary ovarian insufficiency has been established [13].…”